Current Management of Hypertensive Crisis

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DR. Dr. H. DJOKO TRIHADI, Sp.PD, FCCPRSUD Kota Semarang – SMF Penyakit Dalam

Epidemiology of Hypertensive Emergency (HE)

First described by Volhard and Fahr (1914), who saw patients with severe hypertension accompanied by signs of vascular injury to the heart, brain, retina, and kidney.

Prior to the introduction of antihypertensive medications, ñ 7% of hypertensive pts had HE.

Currently, 1 to 2% of pts with hypertension will have a HE at some time in their life.

Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

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Definitions

Hypertensive Crisis BP > 180/120

Hypertensive Urgency Hypertensive Emergency

Markedly elevated BP Markedly elevated BP without severe symptoms or with acute or progressing

progressive target organ damage. target organ damage. BP should be reduced within hours. BP should be reduced immediate.

Oral agents. Parenteral agents.

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9 th Ed,

Lippincott Williams & Wilkins 2006:609-630

Definitions (cont'd)

Accelerated malignant hypertension represents markedly elevated BP with papiledema (grade 4 Keith-Wagener retinopathy) and/or hemorrhages and exudates (grade 3 Keith-Wagener retinopathy). The Clinical features and prognosis are similar with grade 3 or 4 retinopathy (Ahmed et al., 1986)

Hypertensive encephalopaty is a sudden, marked elevation of BP with severe headache and altered mental status, reversible reduction of BP.

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th

Ed, Lippincott Williams & Wilkins 2006:609-630

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Keith-Wagner Classification System

Grade I: Change in ratio of arteriole-venule

diameter. Grade II : Arteriovenous nicking "copper wire"

appearance. Grade III: Focal or diffuse arteriolar spasm,

flame hemorrhages, cotton wool spots, exudate, silver wire appearance, right-angle deviation.

Grade IV: Papilledema, vessel obstruction.

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Pathophysiology: Mechanism of malignant hypertension

Critical degree of hypertension

Increase in vasoconstrictors Endothelial damage (renin-angiotensin, vasopressin,

cathecolamines) Platelet and fibrin deposition

Further BP increase

Intravascular hemolysis

Pressure natriuresis

Fibrinoid necrosis and Intimal proliferation Hypovolemia

Further release of vasoconstrictors

Increase in BP and ischemia

Etiology Essential hypertension Renal parenchymal etiologies: Glomerulonephritis,

tubulointerstitial nephritis, Systemic disorders with renal involvement: SLE,

vasculitides. Renovascular: atheroma, fibromuscular dysplasia Endocrine: pheocromocytoma, Conn's syndrome,

Cushing syndrome Drugs : cocain, amphetamine, clonidine withdrawal, etc Tumor related Coarctation of the aorta Pre-eclampsia/ eclampsia Kitiyakara C, Guzzman NJ.J Am Soc Nephrl 1998:133-42

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Clinical Presentation

30%

25% 25%

23%

20%

16%

14% 15% 12%

10%

5% 5%

2%

0% Cerebral ICH or SAH Hypertensive Acute Acute CHF AMI or UAP Aortic Infarction encephalopathy pulmonary dissection

edema Zampaglione B, Pascale C et al. Hypertension 1996;27:144-7

Initial Evaluation of Patients with a Hypertensive Emergency History :

- Prior diagnosis and treatment of HT - Intake of pressor agents : street drugs,

sympathomimetics - Symptoms of cerebral, cardiac, and visual dysfunction

Physical exam. - BP - Funduscopy - Neurologic status - Cardiopulmonary status - Body fluid volume assessment - Peripheral pulses

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Initial Evaluation of Patients with a Hypertensive Emergency

Lab. evaluation - Hematocrit and blood smear - Urine analysis - Automated chemistry : creatinine, glucose, electrolytes - Plasma renin activity and aldosterone (if primary aldosteronism

is suspected) - Plasma renin activity before and 1 h after 25 mg captopril (if

renovascular hypertension is suspected) CXR (if heart failure or aortic dissection is suspected) ECG

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Autoregulation mechanism

CBF

Normal Mean Arterial Pressure (mmHg)

Chronic Hypertension 11

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Management of Hypertensive Emergency Patients should be admitted to an ICU for

continuous monitoring of BP and parenteral administration of an appropriate agent

Initial goal therapy is to reduce MAP by no more than 25% (within min. to 1 hour).

Then if stable, to 160/100 to 110 mmHg within the next 2 to 6 hours.

Excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided.

Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70

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Management of Hypertensive Emergency (cont'd)

If this level of BP is well tolerated and the patients is clinically stable, further gradual reductions toward a normal BP can be implemented in the next 24 to 48 h.

Exceptions : 1. Ischemic stroke

2. Aortic dissection SBP should < 100 mmHg

3. Patients whom BP is lowered to enable the use of thrombolytic agents

Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70

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Parenteral Drugs for Treatment of Hypertensive Emergencies based on JNC 7

Dose Onset Duration of Action

Sodium Immediate 1-2 minutes after nitroprusside infusion stopped

NTG 5-500 ug/min 1-3 minutes 5-10 minutes

Labetalol HCl 20-80 mg every 10-15 min 5-10 minutes 3-6 minutes or 0.5-2 mg/min

Fenoldopam HCl 0.1-0.3 ug/kg/min <5 minutes 30-60 minutes

Nicardipine HCl 5-15 mg/h 5-10 minutes 15-90 minutes

Esmolol HCl 250-500 ug/kg/min IV 1-2 minutes 10-30 minutes bolus, then 50-100 ug/kg/min by infusion; may repeat bolus after 5 min or increase infusion to 300 ug/min

Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70

Parenteral Drugs for Treatment of Hypertensive Emergencies based on ASA Guideline

Drug I.V. Bolus Dose Continous Infus Rate

5 - 20 mg every 15' Labetalol 2 mg/min (max 300mg/d)

Nicardipine NA 5-15 mg/h

Esmolol 250 ug/kg IVP loading dose 25-300 ug/kg/m

Enalapril 1,25-5 mg IVP every 6 h NA 5 - 20 mg IVP every 30' Hydralazine 1,5-5 ug/kg/m

Nipride NA 0,1-10 ug/kg/m

NTG NA 20-400 ug/m

This parenteral drugs are approved for hypertensive emergency 15 in acute ischemic stroke and ICH

AHA/ASA Guideline, 2007 update. Stroke. 2 007;38: 2001-23.

Parenteral Drugs for Treatment of Hypertensive Emergencies based on CHEST 2007

Acute PE / Systolic Nicardipine, fenoldopam, or nitropruside combined with dysfunction NTG and loop diuretic

Acute PE/ Diastolic Esmolol, metoprolol, labetalol, verapamil, combined with dysfunction low dose of NTG and loop diuretics

Acute Ischemia Coroner Labetalol or esmolol combined with diuretics

Hypertensive encephalopaty Nicardipine, labetalol, fenoldopam

Acute Aorta Dissection Labetalol or combined Nicardipine and esmolol or combine nitropruside with esmolol or IV metoprolol

Preeclampsia, eclampsia Labetalol or nicardipine

ARF / microangiopathic Nicardipine or fenoldopam anemia

Sympathetic crises/ cocaine Verapamil, diltiazem, or nicardipine combined with overdose benzodiazepin

Acute postoperative Esmolol, Nicardipine, Labetalol hypertension

Acute ischemic stroke/ ICH Nicardipine, labetalol, fenoldopam

Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

Actions to increase organ blood flow Pharmacodynamic action

Nicardipine: 3 ? g/kg/min ? 20 min

( ? %) (Hypertensive patients, n = 9) Mean BP Vertebral Renal Coronary artery blood flow blood flow Blood

flow change rate

60 blood flow

Baseline value 40

103 ? 11 mmHg Mean blood pressure

20 Vertebral artery 183 ? 65 mL/min blood flow

Renal artery 563 ? 29mL/min 0 blood flow Mean

blood pressure

Coronary artery 121 ? 42 mL/min change rate blood flow -10

- 20

( ? %) (Shoji Suzuki, et al., The 20th Annual Scientific Meeting of the Japanese Society of Hypertension: 1997)

Special Condition: Stroke

To recent consensus, decreasing BP in acute phase of ischemic stroke is allowed only if : - Ischemic Stroke with BP >220/120. - Candidate of rtPA therapy : BP >185/110. - Hemorrhage stroke with BP >180/100. - Acute stroke in hypertensive patients with hypertensive

encephalopathy, aortic dissection, acute MCI, acute lung edema and ARF.

Choose parenteral antihypertensive drugs and do the BP control cautiously

Labetalol and Nicardipine has been demonstrated to be an effective agent for the control of BP in patients with Ischemic Stroke and ICH. InaSH-2009 23

Special Condition: Preeclampsia and Eclampsia Initial therapy of preeclampsia includes volume

expansion, Mg SO4 for seizure prophylaxis , and BP control.

Delivery is definite treatment for preeclampsia and eclampsia

Based on current data, suggest that hydralazine and nifedipine not be used as first line treatment of severe hypertension in pregnancy.

IV labetalol or nicardipine , which are easier to titrate and appear to be safe and effective.

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Special Condition: ARF

Elevated BP causes deterioration of renal

function, therefore lowering BP is required Therapy should reduce BP without

compromising the RBF or GF Preferred agents : Nicardipine or

fenoldopam, because of it has been show to reduce BP, but still maintain and increase blood flow to renal artery.

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Special Condition: LV failure and PE Acute heart failure occurs as a result of an acute

rise in systemic vascular resistance and reduced LV compliance.

Acute PE / Systolic dysfunction : Nicardipine,

fenoldopam, or nitropruside combined with NTG and loop diuretic

Acute PE/ Diastolic dysfunction : Esmolol,

metoprolol, labetalol, verapamil, combined with low dose of NTG and loop diuretics

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Special Condition: Post operative hypertension Acute postoperative hypertension has been

defined as a significant elevation in BP during the immediate postoperative period that may lead to serious neurologic, cardiovascular, or surgical site complications.

Pain and anxiety are common contributors to BP elevations and should be treated before administration of antihypertensive therapy.

Labetalol, esmolol, nicardipine ,and clevedipine have proven effective in the management of APH.

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Conclusion Patients with hypertensive emergencies require

the immediate reduction of the elevated BP to prevent and arrest progressive end organ damage.

The best clinical setting to achieve this control is in the ICU .

There are several antihypertensive agents available including esmolol, nicardipine , labetalol, and fenoldopam.

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