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HYPERTENSION IN PREGNANCY
(Summary of the CHS guidelines)
February, 2004Nicolas Szecket
(From New Zealand)
Objectives
1. Classification of HTN in pregnancy
2. When to initiate treatment and when to admit
3. Pharmacologic and non-pharmacologic management of HTN in pregnancy
4. Management of severe HTN in pregnancy
5. Overview of Pre-eclampsia
References1. Canadian Hypertension Society Consensus Conference,
CMAJ, Sept. 15, 1997; 157 (6).
2. Fortnightly review: management of hypertension in pregnancy, Magee, LA et al. BMJ 1999; 318:1332.
3. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis, Von Dadelszen, P et al. Lancet 2000; 355:87.
4. UpToDate – various modules
5. The Magpie Trial, Lancet 2002 Jun 1;359(9321):1877-90.
Introduction
Hypertension in Pregnancy:• Major cause of maternal and perinatal morbidity
and mortality• Complicates up to 10% of pregnancies• Second leading cause of maternal mortality in the
developed world (after VTE)• ~1/3 of all maternal deaths are from HTN’sive
disorders
Severe complications
MATERNAL
• CVA• DIC• End-organ failure• Placental abruption
FETAL
• IUGR• Prematurity• Intra-uterine death
The Case
• 34 year old G2P1 at 28 weeks gestation• Sent to you for a BP of 160/98 mm Hg in GP’s
office the previous day• No previous medical problems• No smoking and on no meds• Review of antenatal record shows her BP was
145/90 at 14 and 18 weeks gestation
From this information alone you conclude:
A) She has pre-eclampsia
B) She likely has pre-existing hypertension
C) She needs immediate delivery
D) She has underlying renal disease
BP
Weeks
~20 wks0 wks
15 mm Hg
Grading of Recommendations
• Grade A – Very strong evidence
• Grade B – Fair evidence
• Grade C – Poor studies
• Grade D – Expert opinion
A word about technique(all Grade B evidence)
• Use a mercury sphygmomanometer• Cuff size 1.5 X the patient’s upper arm
circumference• Patient should be at rest for 10 mins prior to
measurement• Patient in sitting position• Cuff at level of heart• Use phase IV Korotkoff (ie, muffling)
Back to the Case
• She remains asymptomatic and states there are good fetal movements
• Exam shows her to be overweight• BP is 155/98• No pitting edema, reflexes are brisk, but no clonus• There is no evidence of any secondary cause of
HTN• Urinary dipstick is negative for protein
Appropriate measures at this point include:
A) Laboratory investigations
B) 24 hour urine collection for protein
C) Admission to hospital
D) All of the above
E) A and B
Definitions• HTN defined as DBP > 90 mm Hg (D)• Severe HTN is > 110 mm Hg (D)• All reading > 90 mm Hg must be confirmed 4
hours later with 2nd reading (D)– Except when > 110 mm Hg
• Significant proteinuria defined as > 0.3 g/day using a 24 hr urine collection (increased from 0.15 g/day in non-pregnancy) (A)
• Severe proteinuria is > 3 g/day• Edema and weight gain no longer used to
diagnosis of PET
CHS classification Interpretation
Pre-existing HTN
Essential hypertension
Secondary
Pre-existing HTN
Essential hypertension
Secondary causes
Gestational HTN without proteinuria “Pregnancy-Induced” HTN
Gestational HTN with proteinuria Pre-eclampsia
Pre-existing HTN + superimposed gestational HTN with proteinuria
Pre-existing HTN with superimposed pre-eclampsia
Unclassifiable
Classification of Hypertensive Disorders in Pregnancy
When do you initiate therapy?(Grade D)
• Immediately: SBP > 169 or DBP > 109 symptomatic
• After 1-2 hrs: SBP > 169 or DBP >109 asymptomatic
• After few days observation:
SBP > 139 or DBP > 89 if PET/underlying problems
SBP > 149 or DBP > 94 if otherwise
When do you admit to hospital?
• Mandatory: SBP > 169, DBP > 109 symptomatic• Strongly recommended:
– Pre-eclampsia– anyone with DBP > 99– anyone you can’t monitor closely as outpatient
• Recommended :– anyone with DBP 90-99 that you want to
follow closely– to assess fetal well-being
Note: for purposes of RC exam, it is never wrong to admit for a few days of monitoring
Back to the Case...
This woman likely had pre-existing hypertension given that she had a diastolic blood pressure of 90 mm Hg prior to 20 weeks’ gestation (answer B).
• HTN at 28 weeks gestation raises the possibility of PET• Should have appropriate initial investigations• Admission is debatable, but most prudent thing to do• Allows for fetal assessment, collection of urine to rule out
PET, and monitoring of blood pressure (answer D)Note: Some centres have “Obstetric Day Units”, an
acceptable option
Which investigations would be appropriate on admission?
(mostly Grade C + D)• CBC, blood film• Lytes, BUN, Creat• Uric acid (Grade B) – may reflect severity• Liver enzymes• Coags• 24 hr urine for protein• Urinalysis (Grade A)• OB to see + BPP/NST/FMC/doppler flow…
Back to the case
• Our patient is admitted to hospital and monitored closely
• Fetal ultrasound is normal• Bloodwork is normal• 24 urinary protein excretion is 0.20 g/day• Her DBP remains 95-105
You would like to begin treatment.What would you prescribe?
Management of Mild-Moderate HTN in pregnancy
• First line drug: Methyldopa (grade A)
• Second line drugs:– Labetalol/Pindolol/Oxprenolol/Nifedipine(grade A/B)
• Third line drugs:– Hydralazine + clonidine (A)– Hydralazine + metoprolol (A)– Clonidine (B)
• Diuretics - only in specific situations
DRUGS TO AVOID:
•ACE- inhibitors
•Angiotensin II receptor antagonistsGoal of therapy: DBP
80-90 mm Hg (grade D)
Beyond the guidelines...
• Lancet, January 2000– meta-analysis– 45 trials including 3773 women
• Aggressive lowering of BP can cause LOW BIRTH WEIGHT (100-200 grams!)
• Guidelines will likely be modified soon• Most experts now aim to keep HTN’sive
pregnant women at BP 150-160/90-100
Outcomes of treatment
Perinatal death
Methydopa - in women with pre-existing HTN
Outcomes of treatment
Prevention of severe HTN
Methydopa in women with pre-existing HTN
Beta-blockers/Nifedipine/combination therapy with hydralazine
Outcomes of treatment
Superimposed PET
NO known pharmacologic prevention
Outcomes of treatment
Preterm delivery
No good data
Outcomes of treatment
IUGR
Poor evidence
?Maybe Beta blockers cause IUGR?
?Maybe Diuretics cause IUGR?
What about Non-Parmacologic Treatment and Prevention?
Indicated for SBP> 140mmHg or DBP > 90mmHg
“Non-pharmacologic Rx alone is recommended for women with SBP of 140-150 mmHg or DBP 90-99mmHg in the absence of maternal or fetal risk factors (Grade D)”
Possibly Promising therapies
ASA no role for routine use (Grade B) BUT…low dose ASA reduces incidence of pre-term
delivery and early onset PET in women at risk (Grade A)
Calcium primary prevention of PET does not prevent development of more severe
GESTATIONAL HTN (Grade B) (NEJM 1991, NEJM 1997)
Others...
Bedrest no evidence for efficacy in fact, Grade B evidence that it is not advisable
Exercise no evidence
Stress control no evidence
Increased energy and protein intake Grade B evidence that they are NOT beneficial
Weight reduction not recommended (Grade C)
Na restriction not recommended (Grade C)
Alcohol restriction no evidence
Magnesium not justified (Grade B)
Zinc/iron/folate not beneficial (Grade B)
Back to the Case
• Methyldopa, 250 mg BID is started
• BP drops to 140/88
• Pt. Discharged home
• 2 weeks later - presents to ER with epigastric pain, headache and blurred vision
• BP 190/115
• 3+ protein on dipstick
Each of the following would be appropriate initial therapy except:
A) Labetalol 5-10 mg IV
B) Nifedipine 5 mg PO
C) Metoprolol 50 mg PO
D) Hydralazine 5-10 mg IV
Management of Severe Hypertension in Pregnancy (DBP> 110 mm Hg)
• First line drugs:– Hydralazine (grade B)– Labetalol (grade B)– Nifedipine (grade B)
• Second line drugs: if refractory to above– Diazoxide (grade D)– Sodium nitroprusside (grade D)
• Note: need continuous fetal monitoring
Treatment goal: 90-100 mm Hg
Back to the case...
This patient has severe hypertension in the setting of pre-eclampsia, and is symptomatic
Her blood pressure needs to be lowered acutely, and so oral metoprolol is NOT an appropriate initial choice (Answer C)
Pre-eclampsia
• Multi organ disorder
• Diagnosis after 20 wks gestation– HTN– significant proteinuria
Burden of disease
• Affects 3-14 % of all pregnancies worldwide
• in 2nd pregnancy:– 1 % if Normal 1st preg– 5-7 % if mild PET in 1st preg– 60-80 % if early severe PET in 1st preg
Other Risk Factors
• HTN at start of preg
• FHx
• Multiple pregnancies
• Chronic maternal HTN
• DM
• APLAS
• CTD
• Increased maternal age
• New partner
• Note: smoking reduces the risk of PET
Pre-eclampsia: Presentation
Clinical• headache• vision disturbances• RUQ pain• nausea and vomiting• elevated blood pressure• edema• convulsions
• stroke • cerebral edema• pulmonary edema• retinal detachment
Laboratory• proteinuria >0.3 g/24 hr• high uric acid (indicates
severity)• HELLP syndrome
- hemolysis, high liver enzymes, low platelets • increased hematocrit• elevated PTT, d-Dimers, low
fibrinogen (markers of DIC)
Back to the Case
• She is treated with labetalol 10 mg IV• BP drops to 160/97• Fetal heart tracing is reassuring• Lab tests are as follows: AST 520, ALT 480,
platelets 200, creatinine 100, uric acid 500• She is transferred to labour and delivery, and has a
tonic-clonic seizure
Which of the following is the MOST EFFECTIVE in preventing further seizures?
A) DilantinB) DiazepamC) Magnesium sulfateD) Control of blood pressure
Eclampsia
• Complicates about 1% of patients with PET• Magnesium sulfate is the treatment of choice:
more effective than dilantin or diazepam in the prevention of further seizures/status eclampticus
• Role of MgSO4 in the primary prevention of PET is controversial, and not yet proven
• Typical loading is 4-6 g IV bolus followed by 1-2 g/hour
• should be continued 12-24 hrs postpartum
• Recent NEJM article comparing MgSO4 to Calcium Channel blocker
• MgSO4 better
Should MgSO4 have been initiated before the seizure?
Probably…
MAGPIE trial• Primary prevention of eclampsia for all
degrees of PET
• NNT = 63 in severe PET
• NNT = 109 in mild-moderate PET
Back to the Case
• patient is treated with MgSO4
• BP controlled with labetalol IV• She undergoes a STAT caesarean section and
delivers a healthy baby boy (taken to NICU…doing well)
• After 24 hrs of monitoring, she is transferred to the ward, and discharged 6 days later
Summary and Editorial comments
• Hypertension in pregnancy is a common medical problem
• Guidelines exist to assist in decision-making, however, most are based mostly on expert opinion
• Some recommendations are certainly “murky” (ie, when to admit, when to start therapy)
• bottom line: never wrong to admit a patient for a few days until pre-eclampsia is safely ruled out
• Don’t forget to ask for OB help from the beginning
THE END