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