Hypertension in Pregnancy Lianne Beck, MD Assistant Professor Emory Family Medicine

OBJECTIVES Know criteria for the diagnosis of chronic hypertension, gestational hypertension and preeclampsia List criteria for the diagnosis of severe preeclampsia/HELLP syndrome Discuss current management considerations

Introduction Most common medical complication of pregnancy 6 to 8 % of gestations in the US. In 2000, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy defined four categories of hypertension in pregnancy: Chronic hypertension Gestational hypertension Preeclampsia Preeclampsia superimposed on chronic hypertension As a group these occur in 12 to 22% of pregnant patients and are directly responsible for approximately 18% of maternal mortality nationally. Complications of hypertension are the third leading cause of pregnancy-related deaths, superseded only by hemorrhage and embolism.

Chronic Hypertension Defined BP measurement of 140/90 mm Hg or more on two occasions Before 20 weeks of gestation OR Persisting beyond 12 weeks postpartum

Chronic Hypertension Treatment of mild to moderate chronic hypertension neither benefits the fetus nor prevents preeclampsia. Excessively lowering blood pressure may result in decreased placental perfusion and adverse perinatal outcomes. When BP is 150 to 180/100 to 110 mm Hg, pharmacologic treatment is needed to prevent maternal end-organ damage.

Treatment of Chronic Hypertension Methyldopa , labetalol, and nifedipine most common oral agents. AVOID: ACEI and ARBs, atenolol, thiazide diuretics Women in active labor with uncontrolled severe chronic hypertension require treatment with intravenous labetalol or hydralazine. ACEI/ARBs not used because of teratogenicity, intrauterine growth restriction (IUGR), and neonatal renal failure. The beta blocker atenolol has been associated with IUGR Thiazide diuretics exacerbate intravascular fluid depletion if superimposed preeclampsia develops.

Gestational Hypertension Formerly called PIH (Pregnancy Induced HTN) HTN without proteinuria occurring after 20 weeks gestation and returning to normal within 12 weeks after delivery. 50% of women diagnosed with gestational hypertension between 24 and 35 weeks develop preeclampsia.

Older Criteria for Gestational HTN 30/15 increase in BP over baseline levels No longer appropriate 73% of patients will exceed 30 mm systolic and 57% will exceed 20 mm diastolic

Preeclampsia New onset hypertension with proteinuria after 20 weeks gestation. Resolves by 6 weeks postpartum. Characterized as mild or severe based on the degree of hypertension and proteinuria, and the presence of symptoms resulting from involvement of the kidneys, brain, liver, and cardiovascular system

Pregnancy-associated factors Chromosomal abnormalities Hydatidiform mole Hydrops fetalis Multifetal pregnancy Oocyte donation or donor insemination Structural congenital anomalies Urinary tract infection Maternal-specific factors Age greater than 35 years Black race Family history of preeclampsia Nulliparity Preeclampsia in a previous pregnancy Specific medical conditions: gestational diabetes, type I diabetes, obesity, chronic hypertension, renal disease, thrombophilias Stress Paternal-specific factors First-time father Previously fathered a preeclamptic pregnancy in another woman

Risk Factors Family history of PIH 5:1 Twin gestation 4:1 RISK RATIO Renal disease 20:1 Chronic hypertension 10:1 Antiphospholipid syndrome Family history of PIH 5:1 Twin gestation 4:1 Nulliparity 3:1 Age > 40 Diabetes mellitus 2:1 African American 1.5:1

Diagnostic Criteria for Preeclampsia SBP of 140 mm Hg or more or a DBP of 90 mm Hg or more on two occasions at least six hours apart after 20 weeks of gestation AND Proteinuria – 300 mg in a 24-hour urine specimen or 1+ or greater on urine dipstick testing of two random urine samples collected at least four hours apart. A random urine protein/creatinine ratio < 0.21 indicates that significant proteinuria is unlikely with a NPV of 83%. Generalized edema (affecting the face and hands) is often present in patients with preeclampsia but is not a diagnostic criterion. Random urine dipsticks can be affected by variable excretion, maternal dehydration, and bacteriuria. The increased glomerular filtration rate of pregnancy lowers serum creatinine, and levels greater than 0.9 mg per dL (80 µmol per L) are abnormal in pregnancy

HELLP Syndrome Is a variant of severe preeclampsia Occurs in up to 20% of pregnancies complicated by severe preeclampsia. Variable clinical presentation; 12 to 18% are normotensive and 13% do not have proteinuria. At diagnosis, 30% of women are postpartum, 18% are term, and 52% are preterm. From 4 to 14 percent of women with preeclampsia present with superimposed HELLP syndrome. HELLP syndrome may be a variant of preeclampsia or a separate entity, but its development is ominous because mortality or serious morbidity occurs in 25 percent of affected women.

HELLP Syndrome Common presenting complaints are RUQ or epigastric pain, N/V, malaise or nonspecific symptoms suggesting an acute viral syndrome. Any patient with these symptoms or signs of preeclampsia should be evaluated with CBC, platelet count, and liver enzymes. When platelet count < 50,000/mm3 or active bleeding occurs, coagulation studies needed to R/O DIC.

Prevention of Preeclampsia Routine supplementation with calcium, magnesium, omega-3 fatty acids, or antioxidant vitamins is ineffective. Calcium reduces the risk of developing preeclampsia in high-risk women and those with low dietary calcium intake. Low-dose aspirin (75 to 81 mg per day) is effective for women at increased risk of preeclampsia, NNT = 69 ; NNT = 227 to prevent one fetal death. Low-dose aspirin is effective for women at highest risk from previous severe preeclampsia, diabetes, chronic hypertension, or renal or autoimmune disease, NNT = 18.

Multiorgan Effects of Preeclamsia Cardiovascular – HTN, increased cardiac output, increased systemic vascular resistance, hypovolemia Neurological – Seizures-eclampsia, headache, cerebral edema, hyperreflexia Pulmonary – Capillary leak, reduced colloid osmotic pressure, pulmonary edema

Multiorgan Effects cont…. Hematologic – Volume contraction, elevated hematocrit, low platelets, anemia due to hemolysis Renal – Decreased GFR, increased BUN/creatinine, proteinuria, oliguria, ATN Fetal – Increased perinatal morbidity, placental abruption, fetal growth restriction, oligohydramnios, fetal distress

Management of Preeclampsia The ultimate cure is DELIVERY. Assess gestational age Assess cervix Fetal well-being Laboratory assessment Rule out severe disease

Gestational HTN at Term Delivery is always a reasonable option if term If cervix is unfavorable and maternal disease is mild, expectant management with close observation is possible

Mild Gestational HTN Not at Term Rule out severe disease Conservative management Serial labs Twice weekly visits Antenatal fetal surveillance Outpatient versus inpatient

An NST is considered reassuring if there are at least 2 accelerations of the fetal heart rate of at least 15 beats per minute over the baseline, lasting at least 15 seconds, occurring within a 20-minute time block. This is called a reactive NST. BPP - The test uses ultrasound to look at fetal movement, fetal body tone, fetal breathing efforts, and amniotic fluid volume. Each of the four parameters is given a score of either zero or two points and then totaled up; if the results of the non-stress test were good, another two points is added. A high score (8-10) correlates with a fetus in good condition, while a low score (0-4) often indicates a fetus who might be better off receiving appropriate care outside the uterus. A score of 6 usually requires a repeat test within 12 to 24 hours. Amniotic Fluid Index(AFI) is traditionally the addition of the four pockets, with the normal range from 8 to about 18

Indications for Delivery in Preeclampsia Fetal indications Severe intrauterine growth restriction Nonreassuring fetal surveillance Oligohydramnios

Indications for Delivery in Preeclampsia Maternal indications Gestational age of 38 weeks or greater Platelet count below 100,000 Progressive deterioration of hepatic or renal function Suspected placental abruption Persistent severe headache or visual changes Persistent severe epigastric pain, nausea, or vomiting Eclampsia

Criteria for Treatment Diastolic BP > 105-110 Systolic BP > 200 Avoid rapid reduction in BP Do not attempt to normalize BP Goal is DBP < 105 not < 90 May precipitate fetal distress

Hypertensive Emergencies Fetal monitoring IV access IV hydration to maintain urine output > 30 mL per hour, limit to 100 mL per hour. The reason to treat is maternal, not fetal May require ICU Excessive fluid administration can result in pulmonary edema, ascites, and cardiopulmonary overload, whereas too little fluid exacerbates an already constricted intravascular volume and leads to further end-organ ischemia.

Characteristics of Severe HTN Crises are associated with hypovolemia Clinical assessment of hydration is inaccurate Unprotected vascular beds are at risk, ie., uterine

Key Steps Using Vasodilators 250-500 cc of fluid, IV Avoid multiple doses in rapid succession Allow time for drug to work Maintain LLD position Avoid over treatment

Acute Medical Therapy Hydralazine Labetalol Nifedipine Nitroprusside Clonidine

Hydralazine Dose: 5-10 mg every 20 minutes Onset: 10-20 minutes Duration: 3-8 hours Side effects: headache, flushing, tachycardia, lupus like symptoms Mechanism: peripheral vasodilator

Labetalol Dose: 20 mg, then 40, then 80 every 20 minutes, for a total of 220mg Onset: 1-2 minutes Duration: 6-16 hours Side effects: hypotension Mechanism: Alpha and Beta blockade Note that labetalol therapy should not be used in women with asthma or congestive heart failure

Nifedipine Dose: 10 mg po, not sublingual Onset: 5-10 minutes Duration: 4-8 hours Side effects: chest pain, headache, tachycardia Mechanism: CA channel blockade

Clonidine Dose: 1 mg po Onset: 10-20 minutes Duration: 4-6 hours Side effects: unpredictable, avoid rapid withdrawal Mechanism: Alpha agonist, works centrally

Nitroprusside Dose: 0.2 – 0.8 mg/min IV Onset: 1-2 minutes Duration: 3-5 minutes Side effects: cyanide accumulation, hypotension Mechanism: direct vasodilator

Seizure Prophylaxis Magnesium sulfate Loading dose of 4 to 6 g diluted in 100 mL of normal saline, given IV over 15 to 20 minutes, followed by a continuous infusion of 1-2 g per hour Monitor urine output, RR and DTR’s With renal dysfunction, may require a lower dose

Magnesium Sulfate Is NOT a hypotensive agent Works as a centrally acting anticonvulsant Also blocks neuromuscular conduction Serum levels: 4-7 mg/dL Additional benefit of reducing the incidence of placental abruption

Toxicity Respiratory rate < 12 DTR’s not detectable Altered sensorium Urine output < 25-30 cc/hour Antidote: 10 ml of 10% solution of calcium gluconate 1 g IV over 2 minutes. Serum magnesium levels should be monitored in women with elevated serum creatinine levels, decreased urine output, or absent deep tendon reflexes. Magnesium toxicity can lead to respiratory paralysis, central nervous system depression, and cardiac arrest!!

Eclampsia New onset of seizures in a woman with pre-eclampsia. Preceded by increasingly severe preeclampsia, or it may appear unexpectedly in a patient with minimally elevated blood pressure and no proteinuria. Blood pressure is only mildly elevated in 30-60% of women who develop eclampsia. Occurs: Antepartum - 53%, intrapartum - 19%, or postpartum - 28% Late postpartum (more than 48 hours after delivery) onset of eclampsia was traditionally thought to be rare; however, a study of 29 cases of postpartum eclampsia demonstrated that 79 percent occurred in the late postpartum period Eclamptic seizures are relatively rare and occur in less than 1 percent of women with preeclampsia.1

Treatment of Eclampsia Protecting the patient and her airway Place patient on left side and suction to minimize the risk of aspiration Give oxygen Avoid insertion of airways and padded tongue blades IV access Mag Sulfate 4-6 g IV bolus, if not effective, give another 2 g Magnesium sulfate is the drug of choice because it is more effective in preventing recurrent seizures than phenytoin (Dilantin) or diazepam (Valium).

Alternate Anticonvulsants Diazepam 5-10 mg IV Sodium Amytal 100 mg IV Pentobarbital 125 mg IV Dilantin 500-1000 mg IV infusion

After the Seizure Assess maternal labs Fetal well-being Effect delivery Transport when indicated No need for immediate cesarean delivery

Other Complications Pulmonary edema Oliguria Persistent hypertension DIC

Pulmonary Edema Fluid overload Reduced colloid osmotic pressure Occurs more commonly following delivery as colloid oncotic pressure drops further and fluid is mobilized

Treatment of Pulmonary Edema Avoid over-hydration Restrict fluids Lasix 10-20 mg IV Usually no need for albumin or Hetastarch (Hespan)

Oliguria 25-30 cc per hour is acceptable If less, small fluid boluses of 250-500 cc as needed Lasix is not necessary Postpartum diuresis is common Persistent oliguria almost never requires a PA cath

Persistent Hypertension BP may remain elevated for several days Diastolic BP less than 100 do not require treatment By definition, preeclampsia resolves by 6 weeks

Disseminated Intravascular Coagulopathy Rarely occurs without abruption Low platelets is not DIC Requires replacement blood products and delivery Definitive diagnosis depends on the result of: 1. Thrombocytopenia 2. Prolongation of prothrombin time and activated partial thromboplastin time 3. A low fibrinogen concentration 4. Increased levels of fibrin degradation products

Anesthesia Issues Continuous lumbar epidural is preferred if platelets normal Need adequate pre-hydration of 1000 cc Level should always be advanced slowly to avoid low BP Avoid spinal with severe disease

SORT: KEY RECOMMENDATIONS FOR PRACTICE In women without end-organ damage, chronic hypertension in pregnancy does not require treatment unless the patient's blood pressure is persistently greater than 150 to 180/100 to 110 mm Hg. – C Calcium supplementation decreases the incidence of hypertension and preeclampsia, respectively, among all women (NNT = 11 and NNT = 20), women at high risk of hypertensive disorders (NNT = 2 and NNT = 6), and women with low calcium intake (NNT = 6 and NNT = 13). – A

Low-dose aspirin (75 to 81 mg daily) has small to moderate benefits for the prevention of preeclampsia (NNT = 72), preterm delivery (NNT = 74), and fetal death (NNT = 243). The benefit of aspirin is greatest (NNT = 19) for prevention of preeclampsia in women at highest risk (previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease). – B For women with mild preeclampsia, delivery is generally not indicated until 37 to 38 weeks of gestation and should occur by 40 weeks. – C

Magnesium sulfate is the treatment of choice for women with preeclampsia to prevent eclamptic seizures (NNT = 100) and placental abruption (NNT = 100). – A Intravenous labetalol or hydralazine may be used to treat severe hypertension in pregnancy because neither agent has demonstrated superior effectiveness. – B

For managing severe preeclampsia between 24 and 34 weeks of gestation, the data are insufficient to determine whether an "interventionist" approach (i.e., induction or cesarean delivery 12 to 24 hours after corticosteroid administration) is superior to expectant management. Expectant management, with close monitoring of the mother and fetus, reduces neonatal complications and stay in the newborn intensive care nursery. – B Magnesium sulfate is more effective than diazepam (Valium; NNT = 8) or phenytoin (Dilantin; NNT = 8) in preventing recurrent eclamptic seizures. – A

Quiz Which one of the following statements about preeclampsia is correct? A. Magnesium sulfate is the treatment of choice to prevent eclamptic seizures. B. Diazepam (Valium) is more effective than magnesium sulfate in preventing recurrent eclamptic seizures. C. Low-dose aspirin is beneficial for the prevention of preeclampsia in low-risk women. D. An "interventionist" approach is superior to expectant management for severe preeclampsia between 24 and 34 weeks of gestation.

Which of the following agents is/are used to treat a 30-year-old woman (gravida 1, para 0) at 19 weeks of gestation who has had a blood pressure measurement of 160/115 mm Hg on two occasions during her current pregnancy? A. Methyldopa (Aldomet; brand no longer available in the United States). B. Nifedipine (Procardia). C. Labetalol. D. Lisinopril (Prinivil).

Which of the following is/are part of the diagnostic criteria for severe preeclampsia? A. Blood pressure measurement ≥ 160 mm Hg systolic or 110 mm Hg diastolic on two occasions at least six hours apart. B. Blood pressure measurement ≥ 150 mm Hg systolic or 100 mm Hg diastolic on two occasions at least six hours apart. C. Proteinuria ≥ 3 g in a 24-hour urine specimen. D. Proteinuria ≥ 5 g in a 24-hour urine specimen.

References Lawrence L, Fontaine P. Hypertensive Disorders in Pregnancy. American Family Physician. July 1, 2008. Wagner L. Diagnosis and Management of Preeclampsia. American Family Physician. December 15, 2004. ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. No. 33, January 2002. American College of Obstetricians and Gynecologists. Obstet Gynecol 2002;99:159-67. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183(1):S1-S22.