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Internal medicine training session (2)Hypertension
Dr Ahmed Othman AbodoohAssistant lecturer of internal medicine Sohag university
Case (1)
Case (1)
36 yo white female 1048707 PMH minus Recently returned to work 10
weeks after the birth of first child
minus Family history of diabetes minus No history of smoking
Tests Ordered Before Your Visit Today ECG-normal
Labs Cr 09 mgdL Na 135 mmolL glucose 97 mgdL HCT 35 TSH 21 K 42 mmolL Total cholesterol 160 mgdL HDL 66 mgdL LDL 120 mgdL
Vitals HR 88 bpm BP 13889mmHg BMI 23
What is her BP stage
normotensive prehypertension stage 1 hypertension
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case (1)
Case (1)
36 yo white female 1048707 PMH minus Recently returned to work 10
weeks after the birth of first child
minus Family history of diabetes minus No history of smoking
Tests Ordered Before Your Visit Today ECG-normal
Labs Cr 09 mgdL Na 135 mmolL glucose 97 mgdL HCT 35 TSH 21 K 42 mmolL Total cholesterol 160 mgdL HDL 66 mgdL LDL 120 mgdL
Vitals HR 88 bpm BP 13889mmHg BMI 23
What is her BP stage
normotensive prehypertension stage 1 hypertension
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case (1)
36 yo white female 1048707 PMH minus Recently returned to work 10
weeks after the birth of first child
minus Family history of diabetes minus No history of smoking
Tests Ordered Before Your Visit Today ECG-normal
Labs Cr 09 mgdL Na 135 mmolL glucose 97 mgdL HCT 35 TSH 21 K 42 mmolL Total cholesterol 160 mgdL HDL 66 mgdL LDL 120 mgdL
Vitals HR 88 bpm BP 13889mmHg BMI 23
What is her BP stage
normotensive prehypertension stage 1 hypertension
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Tests Ordered Before Your Visit Today ECG-normal
Labs Cr 09 mgdL Na 135 mmolL glucose 97 mgdL HCT 35 TSH 21 K 42 mmolL Total cholesterol 160 mgdL HDL 66 mgdL LDL 120 mgdL
Vitals HR 88 bpm BP 13889mmHg BMI 23
What is her BP stage
normotensive prehypertension stage 1 hypertension
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What is her BP stage
normotensive prehypertension stage 1 hypertension
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What is her BP stage
normotensive prehypertension stage 1 hypertension
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What do you recommend now A Diet and lifestyle modification B Begin drug therapy C Ask her to come back for a
BP recheck in one week D All of the above E A amp C
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
week Follow-up She returns in a week Shersquos begun a daily exercise program and her BP on return is13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
1-week Follow-up she returns in a week Shersquos begun a daily exercise program and her BP on return is 13888 mm Hg What is the correct diagnosis
A Normal BP B Prehypertension C Stage 1 hypertension D Not sure
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Treatment Alternatives What is the best treatment for her at this point
A Diet and lifestyle modification and regular
follow-up of her BP B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Treatment Alternatives What is the best treatment for
Vicki at this point A Diet and lifestyle
modification and regular follow-up of her BP
B Drug therapy C Both of the above D Have her fill out her ldquobucket
listrdquo and enjoy the last year of her life
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Our patient 1-12 year later
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Present Days Everything to be EVIDENCE BASEDhellip
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATIONS
1-5 ndashaddress questions 1 and 2 concerning
thresholds and goals for BP treatment
678 ndash address question 3 concerning selection of
antihypertensive drugs
9 ndash summary of strategies based on expert opinion
for starting and adding antihypertensive drugs
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 2
MR Ali is 70 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14085 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B-Diet modification and
follow up C-both AB
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 1
sect In the general population aged ge60 years
initiate pharmacological treatment to lower BP at
SBP of ge150 mm Hg or
DBP of ge 90mm Hg and
treat to a goal
SBP lt 150 mm Hg and
DBP lt90 mmHg
Strong recommendation ndash Grade A
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Corollary Recommendationsect In the General Population aged ge60 yrs
If pharmacological treatment for high BP results in
lower achieved SBP (for example lt140 mm Hg) and
treatment is not assosciated with adverse effects on
health or quality of life treatment does not need to
be adjusted
Expert opinion ndash Grade E
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 3
MR Hemdan is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B-Diet modification and follow
up C-both AB
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 2
sect In the general population lt 60 yrs
Initiate pharmacological treatment to lower BP
at DBP of ge90 mmHg and
treat to a goal
DBP of lower than 90 mmHg
For ages 30-59 yearsStrong recommendation -Grade A
For ages 18-29 yearsExpert opinion ndashgrade E
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
DBP trials
HDFP(Hypertension Detection and Follow uP)
Hypertension ndash Stroke Cooperative
MRC
ANBP
VA Cooperative
Treatment to a lower DBP goal lower than 90 mm Hg reduces
cerebrovascular eventsHFoverall mortality
No benefit of treatment to a target DBP of 8085 mm Hg compared to
90 mm Hg ndash HOT trial(not statistically significant in outcomes)
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 3
sect In the General Population younger than 60years
initiate pharmacological treatment to lower BP
at SBP of ge140 mm Hg and
treat to a goal SBP of lt 140 mm Hg
Expert opinion ndash Grade E
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 4
MR khaled admitted to hospital with generalized body swelling and decrease in urine output on examination he has genealized anasarca and his BP 13585he has albumin+++ in urine and his 24 hr urinary protein is 5000 mg with serum creatinine is 32 mgdl
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B-no need to start
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What will you do
A- Start antihypertensive drug B- no need
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 4
sect In the Population aged 18 years or older with CKD
Initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg
or
DBP of ge 90 mmHg
and
treat to goal
SBP of lt 140 mm Hg and
DBP lt 90 mm Hg
Expert opinion ndash grade E(Younger lt70 yrs with eGFR or measured GFR lt60 mlmin173m2
People of any age with albuminuria gt30mgalbg of creatinine)
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 5
sect In the Population aged 18 years or older with diabetes
initiate pharmacological treatment to lower BP at
SBP of ge 140 mm Hg or
DBP of ge90 mm Hg
and treat to a
goal SBP lt 140 mm Hg
goal DBP lt 90 mm Hg
Expert opinion Grade E
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Back to MR ALI
MR Ali is 50 year old complaining from headache no evidence of DMor CKD his blood pressure is 14590 at the first reading then 14090 at the second reading
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
With what you will start
A-Thiazide diuretics B-BB C-loop diuretics(Lasix) D-Aldomet
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 6
sect In the General NonBlack populationincluding those with Diabetes
initial AntiHypertensive treatment should include a
Thiazide -type Diuretic
Calcium Channel Blocker(CCB)
Angiotensin Converting Enzyme inhibitor(ACEI)or
Angiotensin Receptor Blocker(ARB)
Moderate recommendation ndashGradeB
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Not recommended as first line drugs
Dual alpha1 +b blocking agents (Carvedilol)
Vasodilating b blocking agents (Nebivolol)
Central a2 adrenergic agonists (Clonidine)
Direct vasodilators (Hhydralazine)
Alodsterone receptor antagonists (Spironolactone)
Peripherally acting adrenergic antagonists (Reserpine)
Loop diuretics(Furosemide)
ONTARGET trial was not eligible because Hypertension was not
required for inclusion in the study(TelmisartanRamipril)
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 7
sect In the General Black population
including those with Diabetes
initial antihypertensive treatment should include a
thiazide ndash type diuretic or CCB
For general black populationModerate Recommendation ndashGradeB
For black patients with diabetesWeak recommendation ndashGradeC
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 8
sect In the population aged 18 years or older
with CKD and hypertension
initial (or add-on) antihypertensive treatment should include
ACEI or ARB to improve kidney outcomes
This applies to all CKD patients with hypertension regardless
of race or diabetes status
Moderate Recommendation ndash GradeB
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What if patient is a black and having CKD
In black patients with CKD and proteinuriaan ACEI or ARB is
recommended as initial therapy because of the higher likelihood
of progression to ESRD AASK trial
JAMA2002288(19)2421-2431
In black patients with CKD but without proteinuriathe choice
for initial therapy is less clear and includes a thiazide- type
diureticCCBACEI or ARB
ACEI ARB can be used as an initial drug or second line drug
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 5
Fahmy Amer 55 yo male presents for follow-up Past Medical History minus Blood pressure on initial presentation was
16095 now 15o90 minus Non-smoker no known CAD minus Fasting glucose 140 mgdL (repeated from
previous visit when it was 142 mgdL) A1C 82 minus Initial therapy Diet modification increased
exercise and started 25 mg of HCTZ
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Next action A Continue dietary modification and
exercise recommendations B Begin therapy with an ACEi ARB
or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Next action A Continue dietary modification
and exercise recommendations B Begin therapy with an ACEi
ARB or CCB C Refer to dietitian for diet
counseling D Begin metformin E All of the above F A amp B only
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 14090 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
2-Week Follow-Up
Mr Amer returns having visited with the dietitian and is trying to implement his recommendations He has started walking daily His BP at this visit is 13684 2hr postprandial glucose is 126 mgdL What should we consider next
A Increase the dose of the ACEiARB or CCB B Consider additional up-titration or new
medications for diabetes High BP or cholesterol as needed
C Initiate a dose of aspirin if not already started D All of the above
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
1-Month Follow-Up
Mr Amer returns for follow-up His BMI is 29 2hr postprandial glucose is 92
mgdL HgA1c is 68 and his BP is
12075
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Trials results have an effecthellip
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
The placebo effecthellip
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Thiazide diuretics Natrilix SR HypotenseIndamide CCCEpilat (3)AdalatNimotopNorvasc(5-
10)alkapresswindipinemyodura
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
ACEIs
CapotencapotrilhypopressEnalapril(5-20) Ezapril(10)Zestril(5-10-20) sinoprilCoversyl(5-10)Tritace(125-25-5-protect)
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
ARBS Tareg(40-80-160) Candesar(4-8)Atacand Erastapex(5-20-40)
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
RECOMMENDATION 9
If goal BP is not reached within a month of treatment
Increase the dose of the initial drug or
add a second drug from one of the classes in recommendation6 (thiazide- type diureticCCBACEIARB)
If goal BP cannot be reached with 2 drugs
add and titrate a third drug from the list provided Donot use an ACEI and ARB together in the same patient If goal BP cannot be reached using the drugs in recommendations because of
a contraindication or the need of gt 3 drugs to reach goal BPantihypertensive drugs from other classes can be used
Referral to a hypertension specialist Expert opinion ndashGradeE
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 6
51 year old man admitted to an outside hospital
CC Sudden onset of left-sided weakness severe headache slurred speech and left facial droop BP 260172 Head CT Scan showed Right basal ganglia
hemorrhage with shift HPI Transported by ambulance to SUH
Intubated en route due to declining mental status
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 6
PMH - Hypertension - according to wife patient was non-adherent with prescribed medications Out patient medications and
allergies - not available Family History +for HTNCVA
Exam SUH - BP 196130 Positive for Left dense hemiparesis
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Case 6
Hospital day 2 Dilated right pupil Emergent right frontotemporal
craniotomy and evacuation of clot Subsequent Hospital Course
Difficult to control BP Pneumonia
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Define his hypertension crisis A-Hypertension emergency B-Hypertension Urgency
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Question 1
What is the primary reason for hypertensive emergencies today
1 Renovascular Disease2 Pheochromocytoma3 Non-adherence to anti-hypertensive
medication4 Hyperaldosteronism5 Erythropoeitin
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What is the primary reason for hypertensive emergencies in the USA today
1 Renovascular Disease
2 Pheochromocytoma
3 Non-adherence to anti-hypertensive medication
4 Hyperaldosteronism
5 Erythropoeitin
10
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Hypertensive Emergency
According to the Joint National Committee on Hypertension Report
Severely elevated blood pressure with signs and symptoms of acute end organ damage
Requires hospitalization Requires parenteral medication
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Hypertensive Urgency
Severely elevated blood pressure without signs and symptoms of acute end organ damage
Can be managed as an outpatient
Can be managed with oral medications
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Hypertensive Emergency
Damage Heart - CHF MI angina
Kidneys - acute kidney injury microscopic hematuria
CNS - encephalopathy intracranial hemorrhage Grade 3-4 retinopathy
VasculatureVasculature - aortic dissection eclampsia
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Epidemiology
Common associationsPrevious history of hypertensionLack of a primary care
physicianNon adherence to
antihypertensive regimenElicit drug use (cocaine)
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Etiology Essential hypertension Inadequate blood pressure control and noncompliance are
common precipitants (MOST COMMON) Renovascular Eclampsiapre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis Post-op hypertension Coarctation of aorta (very rare)
2nd common
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Question 2 What is the most common complaint
in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
What is the most common complaint in hypertensive emergency
1 Neurologic defect2 Gross Hematuria3 Chest pain4 Headache5 Epistaxis
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Clinical Presentation
Variable Zampaglione et al
(Hypertension 27144 1996) 14 209 ER visits in one year
period 108 met definition of hypertensive
emergency (08) Mean Systolic BP 210 + 32 Mean Diastolic BP 130 + 15
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Clinical Presentation
Frequency of signs and symptomsChest Pain 27Dyspnea 22Neuro defect 21Interestinglyhellip
Headache was only 3 and epistaxis was 0 in this study
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Question 3
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 All of the above
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Hypertensive emergency is associated with a threshold BP of
1 Systolic gt 225 mm Hg2 Diastolic gt 110 mm Hg3 Systolic gt 250 mm Hg4 Diastolic gt 120 mm Hg5 Non of the above
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Threshold BP
There is no specific BP where hypertensive emergencies occur
But organ dysfunction is rare with diastolic BPs lt 130 mm Hg Rate of increase may be more important Hence encephalopathy will occur at lower
BPs in pregnancy and in children
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Initial Evaluation
Focused history History of hypertension How well is hypertension controlled What antihypertensives Adherence to antihypertensive regimen Last dose of antihypertensive
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Initial Evaluation
Social HistoryRecreational Drugs
AmphetaminesCocainePhencyclidine
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Initial Evaluation
Confirm BP in both armsUse appropriate sized BP cuffCuff that is too small
BP cuffs that are too small falsely elevate BP measurements in obese patients
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Initial Evaluation
Assess for end-organ damage Vascular Disease
Assess pulses in all extremities Auscultate over renal arteries for bruits
Cardiopulmonary Listen for rales (CHF) Murmurs or gallops
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Initial Evaluation
Neurologic Exam Hypertensive Encephalopathy -
mental status changes nausea vomiting seizures
Lateralizing signs uncommon and suggest cerebrovascular accident
Retinal Exam
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Lab Testing
ECG LVH look for signs of ischemia injury
infarct Renal Function Tests (urine included)
Elevated BUN Creatinine proteinuria hematuria
CBC CXR - pulmonary edema aortic arch
cardiac enlargement
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Lab Testing Aortic Dissection
Suspect with severe tearing chest pain unequal pulses widened mediastinum
Contrast Chest CT Scan or MRI Pulmonary EdemaCHF
Transthoracic Echocardiogram Differentiate between systolic dysfunction
diastolic dysfunction mitral regurgitation
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Management
Elevated BP without target organ damage
Hypertensive urgency Oral meds Goal - gradual reduction of BP
over 24 - 48 hours
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
ORAL DRUGS FOR HTN URGENCIES
Drug Initial dose Onset duration Adverse effects
Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotensionbronchoconstriction
Clonidine 0150-0300 mg 30-60 min 8-16 h Hypotensiondry mouth
Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose)tachycardia
Nicardipine 20-40 mg 30-60 min 8-12 h Headachetachycardia
Amlodipine 5-10 mg 60-120 min 12-18h Headacheflushing
Captopril 25-50 mg 15-45 min 6-8h Renal failure in BRAS
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Management
Elevated BP with target organ damage
Hypertensive emergency Parenteral meds Goal - Reduce diastolic BP by
10-15 or to 110 mm Hg over a period of 30 - 60 minutes
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
GOAL reduce MAP by no more than 20-25
DBP to 100-110mm Hg within few minutes to 2 hours
More aggressive and rapid BP reduction (Acute Pulmonary edema Aortic dissection)
More slowly for acute cerebrovascular damages with monitoring of neurological status
Constant infusion of intravenous agents required (no intermittent IV bolusesoralsublingual drugs- drastic BP fall)
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Normalisation of BP is usually not recommended
How fast and how much BP to be lowered to be given importance
Conditions apply
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Why Sudden fall in BP may cause acute hypoperfusion of vital organs
and results in myocardial ischemia or infarction hemiplegiaor
acute renal failure
Older patients with long lasting hypertension and preclinical
organ involvement (LVH atherosclerosis and arteriolar
remodelling) are at risk of these complications as the lower limit of
autoregulation shifted to right
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Management
Where ICU with close monitoring Severe requires intra-arterial BP
monitoring Which Parenteral meds Depends on the situation
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Question 4
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Which of the following drugs should not be used to treat hypertensive emergency
1 Sublingual Nifedipine
2 Labetolol3 ACE Inhibitors4 Nicardipine5 1 and 3
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Preferred Agents Beta blockers
Labetolol Esmolol
Calcium Entry blocker Nicardipine
Dopamine-1 receptor agonist Fenoldapam
Vasodilators - nitroprussidenitroglucerin
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Sodium nitroprusside
Potent short acting arterial and venous dilator
(reduces pre- and after- load)
Rapid onset of action(seconds)
Continuous intra-arterial BP monitoring required
Infusion chamber and tubing to be covered
intracranial pressure (caution in intracerebral hemorrhage)
Induces coronary steal (non selective coronary vasodilation)
Increases mortality in pts with acute MI (NEJM1982)
Thiocyanate toxicity (nauseavomitinglactic acidosis and altered mental status)
Usually rare seen in pts with renal hepatic dysfunction
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Fenoldopam
A peripheral dopamine-1 receptor antagonist (DA1) highly
specific
10 ndashfold more potent than dopamine as a renal vasodilator
Antihypertensive effect by combined natriuretic and vasodilatory effect (esp
intrarenal arteries)
Not to be used as prophylactic agent for preventing CIN (CAFCIN
Trial)
Agent of choice in hypertensive emergencies assosciated with renal
dysfunction
Adv effects ndash hypotension hypokalemia
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Nicardipine
Second generation DHP CCB
Strong cerebral and coronary vasodilation
Onset of action 5-15 min Duration being 2-6 hrs
Increases both stroke volume and coronary blood flow with a favourable effect on
myocardial oxygen balance
CAD with Systolic HF CI in Aortic stenosis
Dosage independent of weight
Infusion rate of 5mgh ndash 25 mgh increments every 5 min ndashmax being 15 mgh
IV Nicardipine maintained BP in Treatment range gt IV Labetalol (CLUE trial)
J Emerg Med 19875463-473
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Clevidipine
Third generation intravenous dihydropyridine caclium channel antagonistFDA approval (2008)Ultra short half life of about 1 minPotent arterial vasodilation (no effect on venous capacitance myocardial
contractility)No significant adverse effect on heart ratersquo Injectable emulsion999 bound to proteinSafe in pts with renalhepatic dysfunctionCI ndashallergies to soy productseggs and egg productsdefective lipid
metabolism
Rivera et al 2010Polly et al 2011
50mg100ml
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Dosage
bullAn IV infusion at 1ndash2 mghour is recommended for initiation and
should be titrated by doubling the dose every 90 seconds
bull As the blood pressure approaches goal the infusion rate should be
increased in smaller increments and titrated less frequently
bullThe maximum infusion rate for Cleviprex is 32 mghour
bullMost patients in clinical trials were treated with doses of 16 mghour
or less
No more than 1000 mL (or an average of 21 mghour) of Cleviprex infusion is recommended per 24 hours
Am J Cardiovascular Drugs 20099117-134
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Labetalol
Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (17)
Hypotensive effect ndash in 2-5 min after IV admin Maintains cardiac output (unlike other BB) Reduces SVR but does not decrease PBF Cerebralrenalcoronary blood flow maintained
Less placental transfer can be used in pregnancy induced HTN emergency
Metabolised by liver OralIV
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Esmolol
Ultrashort acting cardioselective β adrenergic blocking agent
Ideal β blocker in critical cases
Useful in severe postoperative HTN
Onset of action is within 60 sec
Duration of action being 10-20min
Rapid hydrolysis of ester linkages by RBC esterases(metabolism) not
dependent on renal or hepatic function
05 to 1mgkg loading dose over 1minfollowed by an infusion
-50ugkgmin(max 300ugkgmin)
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Not to useSublingual Nifedipine
Drug is poorly soluble not absorbed through buccal mucosa
Sudden uncontrolled and severe reductions in BPmay precipitate
cerebralrenal and myocardial ischemic events
Lack of clinical documentation attesting to a benefit from its use
The Cardiorenal Advisory Committee of the FDA has concluded ldquothat
the practice of administering SLoral nifedipine should be abandoned
because this agent is not safe nor efficaciousrdquo
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Scenarios
Our Case - Acute ischemic strokecerebrovascular bleed
Agents Fenoldopam Labetolol Nicardipine
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
CVA or Ischemic Stroke
BP elevation after CVA or ischemic stroke can be protective to preserve cerebral perfusion
Hold on aggressive lowering unless Thrombolytic therapy anticipated or BP excessively high ( SBP gt 220 mm
Hg or DBP gt120) BP Goal for thrombolytic therapy is
to lower SBP if gt 185 or DBP gt110
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Cardiac Conditions
Acute Pulmonary Edema with systolic dysfunction Nicardipine Fenoldopam Sodium nitroprusside Nitroglycerin Loop diuretic
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Cardiac Conditions
Acute Pulmonary Edema with diastolic dysfunction Esmolol metoprolol labetolol verapamil Nitroglycerin Loop diuretic
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Cardiac Conditions
Acute myocardial ischemiaEsmolol labetololNitroglycerin
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Sympathetic Crisis
Generally in association with recreational drugs such as cocaine amphetamine or phencyclidine
Sudden cessation of clonidine or Beta-adrenergic antagonist
Pheochromocytoma - rare
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Question 5
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Which of the following drugs should be avoided in sympathetic crises with hypertensive emergency
1 Phentolamine2 Benzodiazepine3 Labetolol4 Nicardipine5 Fenoldopam
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Sympathetic Crisis
Beta-adrenergic antagonists will result in unopposed alpha-adrenergic stimulation
In cocaine use Beta blockers can Increase blood pressure Worsen coronary artery vasoconstriction Decrease survival
Avoid beta blockade (including non selective agents such as labetolol)
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Sympathetic Crisis
Recommended DrugsNicardipineFenoldopamVerapamilBenzodiazepineIf pheo suspected use
phentolamine
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Aortic Dissection
Treatment is paramount 75 of patients with ascending aortic
dissection die in 2 weeks of the acute episode without successful therapy
5 year survival is 75 with successful intervention
Khan et al Chest 2002 122311 Kouchoukos New Engl J Med 1997
3361876
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Aortic Dissection
Vasodilator aloneCauses reflex tachycardiaIncreases cardiac ejection
velocityIncreases aortic shear forcesExtends the dissection
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Aortic Dissection
Standard therapyBeta-adrenergic blocker plus
vasodilatorEsmolol + Nicardipine or
fenoldopamNitroprusside can be used
as well
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Acute Post Operative Hypertension
Frequent in post-operative state (20-75)
Hyper-responsiveness to surgical trauma Increased stress hormones Activation of RAA
Also hypothermia hypoxia carbon dioxide retention bladder distention
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Acute Post Operative Hypertension
Prevention Safe to give antihypertensives pre-op Hold diuretics
Treatment - BP thresholds vary Control pain and anxiety While NPO use nicardipine esmolol
or labetolol Resume oral medications when
possible
Thank you
Questions
Thank you
Questions
