MANAGEMENT OF HYPERTENSION IN PREGNANCY, THE ALGORHITHM Are Particular Anti-hypertensives More Effective or Harmful Than Others in Hypertension in Pregnancy? Existing data is inadequate Methyldopa and thiazide diuretics appear to be safe? Avoid ACE inhibitors and receptor blockers? Safety of atenolol in chronic hypertension 1
Treatment of Chronic Hypertension in Pregnancy Mostwomenwithstage1 with stage to 2 chronic hypertension (low risk) are candidates for nondrug therapy, absent evidence of target organ damage. Most of the increased risk associated with chronic hypertension occurs with superimposed preeclampsia. End points for reinstituting treatment include SBP > 150-160 or DBP > 100-110 or evidence of target organ damage. Low Risk Chronic HTN perinatal outcome Usually good irrespective of antihypertensive drugs Most poor outcomes were related to superimposed preeclampsia Discontinue antihypertensive meds Treat BP > 160/110 mmhg to keep DBP 105 mmhg In absence of superimposed preeclampsia, pregnancy may continue Favorable cervix Favorable cervix Labor Completion of 40 weeks 2
High Risk Chronic HTN Secondary hypertension Maternal age >40 Duration HTN >15 years Target organ damage Previous perinatal loss BP 180/110 mmhg MANAGEMENT OF CHRONIC HTN IN PREGNANCY BEFORE CONCEPTION Evaluation for secondary hypertension Evaluation for target organ damage Change to medications safe for pregnancy Lifestyle planning Baseline laboratory testing Pheochromocytoma Other causes if severe Cardiac function, LVH (echocardiography) Renal disease (serum creatinine, proteinuria) Taper early ( ACEI, ARB ) Titrate later Restrict aerobic exercise Avoid weight reduction Moderate sodium intake Avoid all alcohol and tobacco Hematocrit, hemoglobin, platelet count, serum creatinine, uric acid, urinalysis 3
Chronic BP hypertension MANAGEMENT OF CHRONIC HTN DURING PREGNANCY Selection of medications safe for pregnancy Thresholds for treatment Laboratory ato Monitoring 150-160 mmhg systolic 100-110 mmhg diastolic Hematocrit, hemoglobin, platelet count, serum creatinine, i uric acid, AST, ALT, quantification of urine protein, serum albumin, LDH, peripheral blood smear, coagulation studies Antihypertensive Drug Selection ACEI and ARB are contraindicated in pregnancy. Methyldopa preferred first-line therapy; labetalol if methyldopa not tolerated. Alternatives to methyldopa can be substituted based on rational mechanisms of action. Long-term studies of most other agents are lacking in pregnant women. Diuretics not used as first-line agents but are not contraindicated except in cases of reduced uteroplacental perfusion. 4
ORAL TREATMENT OF HYPERTENSION IN PREGNANCY AGENT Methyldopa Beta Blockers Labetalol Clonidine Calcium Channel Blockers Diuretics COMMENTS Preferred based on long term studies of child development and uteroplacental blood flow Reports of intrauterine growth retardation, particularly for atenolol exposure at conception or in the first trimester; generally safe Increasingly preferred for efficacy and few side effects Limited data Limited data Most experience with nifedipine and isradipine No increase in major teratogenicity with exposure Not first line agents, probably safe Angiotensin Converting Enzyme Inhibitors Angiotensin Receptor Blockers Contraindicated, reports of fetal toxicity and death Contraindicated, reports of fetal toxicity and death MANAGEMENT OF CHRONIC HYPERTENSION IN PREGNANCY DELIVERY Maternal indications Gestational age 38 weeks Platelet t l t count <100,000 000 cells/mm 3 Deterioration in hepatic or renal function Suspected placental abruption Severe headache or visual changes Severe epigastric pain, nausea or vomiting Fetal indications Acute/parenteral therapy Severe fetal growth restriction Concerning fetal testing results Olugohydramnios 5
MANAGEMENT OF CHRONIC HTN IN PREGNANCY POSTPARTUM Lactation Withhold antihypertensive medication Taper medication dosage Selection of safe medications Close monitoring for adverse effects LATE ISSUES AFTER HYPERTENSIVE PREGNANCY Persistent hypertension Long-term risk Evaluation for secondary causes Change medication Monitor blood pressure for future hypertension Treat cardiovascular risk factors Treating Hypertension During Lactation Breastfeeding encouraged (with limits). Little information on excretion of agents in breast milk or long-term effects on exposed infants. No short-term adverse effects reported with methyldopa or hydralazine. Beta-blockers: propanolol & labetalol recommended. No data on calcium antagonists. Diuretics may reduce milk volume/suppress lactation. ACEI and ARB should be avoided. 6
Postpartum Counseling and Followup Counseling for Future Pregnancies Risk of recurrent preeclampsia Preeclampsia before 30 weeks (40%) Multiparas as compared with nulliparas or new father, African Americans. RISK FACTORS FOR RECURRENT HYPERTENSION IN PREGNANCY Early onset of hypertension in a prior pregnancy High baseline blood pressure early in pregnancy Chronic hypertension Persistent hypertension beyond 5 weeks postpartum p 7
Pregnancy, Hypertension, and Renal Disease Renal insufficiency may progress and jeopardize fetal survival. As renal failure progresses, consider sodium restriction, use of loop diuretics, or dialysis. Magnesium sulfate is hazardous in women with severe renal failure; doses should be reduced and guided by plasma magnesium determinations. Phenytoin may be an alternative. Significant maternal morbidity associated with chronic dialysis during pregnancy: conception should be discouraged. Treatment of Acute Severe Hypertension in Pregnancy SBP > 160 mm Hg and/or DBP > 105 mm Hg Parenteral hydralazine is most commonly used. Parenteral labetalol is second-line drug (avoid in women with asthma and CHF.) Oral nifedipine used with caution. (Short-acting nifedipine is not approved by FDA for managing hypertension.) Sodium nitroprusside may be used in rare cases. 8
Drugs Used for Acute Severe Hypertension in Pregnancy-Postpartum AGENT Hydralazine (preferred) Labetalol (second line) DOSAGE 5 mg iv bolus, then 10 mg every 20 to 30 minutes to a maximum of 25 mg, repeat in several hours as necessary 20 mg iv bolus, then 40 mg 10 minutes later, 80 mg every 10 minutes for 2 additional doses to a maximum of 220 mg Nifedipine of 30 mg (controversial) g, Sodium nitroprusside (rarely when others fail) IV Ketanserin 10 mg po, repeat every 20 minutes to a maximum Cautious use with magnesium sulfate, can see precipitous blood pressure drop Short acting nifedipine is not approved by FDA for managing hypertension 0.5 ug/kg/min to a maximum of 5 ug/kg/min Fetal cyanide poisoning may occur if used for more than 4 hour In summary, the implications of the observed impact of the treatment-induced fall in blood pressure on fetal growth must be considered seriously. Women are unlikely to suffer either acute or chronic deleterious effects, over the 9 months of pregnancy, from blood pressures that are below 170/110110 mmhg. At present, we cannot be sure of the impact that anti- hypertensive treatment for mild-to-moderate pregnancy hypertension may have on perinatal outcomes. New data from clinical trials are needed. Von Dadelszen P et al: Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: A meta-analysis analysis Lancet 2000;355 (Jan 8): ):87-92. 9