Essentials of diagnosis: hypertension, proteinuria, ± seizures (eclampsia).
Preeclampsia is defined as new onset of hypertension and either proteinuria or end-organ dysfunction at more than 20 weeks gestational age in previously normotensive women or new onset proteinuria, severe hypertension, or symptoms in women with chronic hypertension. Preeclampsia is a common disorder with an incidence of approximately 15% in nulliparous women and 6% in multiparous women. The disease is also more common at extremes of age.
Hypertensive disorders in pregnancy are one of the leading causes of maternal death in the United States and worldwide. Approximately 75% of preeclampsia will be mild and self-limited. Of the remaining 25% that are severe, very few will require ICU care usually due to significant end-organ damage. Preeclampsia affects the cardiovascular, pulmonary, renal, hepatic, hematologic, and neurologic systems.
Early diagnosis of preeclampsia is imperative to optimize maternal and fetal outcomes. The only “cure” for preeclampsia is delivery, the timing of which is determined based on gestational age and severity of disease.
Symptoms or Signs—Preeclampsia was historically diagnosed based on a triad of hypertension, proteinuria, and edema. Edema has been removed from the diagnostic criteria because of the frequent occurrence of edema in late pregnancy, but a sudden and dramatic weight gain still conveys a high likelihood of imminent preeclampsia. In 2013, ACOG removed proteinuria as an essential criterion for diagnosis of preeclampsia.
Preeclampsia is defined as with or without severe features. Preeclampsia without severe features, generally, does not cause long-term maternal end-organ damage and thus can be managed expectantly until a later gestational age, that is, 37 weeks. Preeclampsia with severe features can present with a wide variety of signs/symptoms and often requires delivery regardless of gestational age (Table 60–2).
Table 60–2Criteria for severe preeclampsia. |Favorite Table|Download (.pdf) Table 60–2Criteria for severe preeclampsia.
Blood Pressure ≥ 160 or ≥110
(2 values at least 4 hours apart)
Central Nervous System Dysfunction
(Cerebral or Visual Disturbances)
(RUQ/epigastric pain, transaminase >= twice normal)
|Thrombocytopenia (< 100K platelets/microL) |
(serum creatinine > 1.1 mg/dL or doubling)
|Pulmonary Edema |
|Seizures (Eclampsia) |
Classically, the minimum criteria for diagnosis of mild preeclampsia are blood pressure greater than 140 mm Hg systolic or 90 mm Hg diastolic on 2 separate occasions greater than 4 hours apart and proteinuria defined as 300 mg of protein in a 24 hours urine collection or at least 30 mg/dL (1+) protein on a spot urine dipstick. There has been a shift to using a urine protein/creatinine ratio of more than or equal to 0.3 to diagnose proteinuria.
Recent guidelines published by the ACOG in December 2013 encourage new diagnostic criteria for preeclampsia excluding the requirement for proteinuria for diagnosis. The authors state that evidence suggests that kidney damage can occur in the setting of preeclampsia without significant proteinuria.
Preeclampsia is generally a clinical diagnosis. Laboratory data are useful in following the course of the disease, particularly in the case of expectant management due to prematurity of the fetus. Serial monitoring of hemoglobin, platelet count, creatinine, liver function tests, lactate dehydrogenase (LDH), and creatinine are essential.
Delivery—The only definitive management for preeclampsia is delivery of the fetus. In the case of severe preeclampsia, delivery is often expedited except in specific situations including extreme prematurity. Even in these cases, the delay is often brief and used to administer corticosteroids for fetal lung maturity or facilitate transfer to a tertiary care center.
Seizure Prophylaxis—Seizure prophylaxis should be administered to all patients in whom severe preeclampsia is diagnosed or suspected. Seizure prophylaxis is continued through delivery and 24 hours postpartum or until the patient has proven stable enough to attempt expectant management.
In the United States, magnesium sulfate is the most common medication administered for seizure prophylaxis. It is generally administered as an intravenous drip, but can be given intramuscularly if intravenous access is not available. The usual regimen includes a 4 to 6 g loading dose given over 30 minutes, followed by a continuous infusion of 2 g/h. The therapeutic range is wide with goal serum magnesium levels of 4.8 to 8.4 mg/dL.
Magnesium toxicity should be monitored for clinically in alert patients with physical exam (reflexes and cognitive status). Laboratory values can also be monitored. Magnesium is contraindicated in patients with myasthenia gravis and relatively contraindicated with pulmonary edema. It should be used with caution and consideration for dosage modification in the setting of significant renal dysfunction or oliguria. The second-line medication for treatment in these cases is phenytoin.
Control of Hypertension—Severe hypertension (BP > 160/110) should be controlled aggressively. Hydralazine and labetalol are the most common medications used to treat acute hypertension in pregnancy. Hydralazine is administered in 5 to 20 mg doses based on patient response at 30 minute intervals. Labetalol is administered starting at a 20 mg dose and can be doubled every 10 minutes up to an 80 mg dose and a maximum total of 220 mg.
The goal is to lower blood pressure out of the severe range, not to achieve a normal blood pressure. If repetitive IV doses of medication are unable to control the blood pressure, IV drips of nitroglycerin, nicardipine, or nitroprusside can be used in a monitored ICU setting. In the setting of refractory hypertension, delivery is required once the mother is stabilized. Nitroprusside administration can lead to fetal cyanide poisoning and thus should be used with caution prior to delivery of the fetus.
Physicians should exercise caution when using any vasodilators in patients with preeclampsia because patients are often intravascularly depleted making them susceptible to dramatic drops in blood pressure. Significant drops in blood pressure can lead to decreased uteroplacental perfusion and fetal compromise.
Hemodynamic Monitoring—Invasive monitoring is not contraindicated in pregnancy and can be considered in the case of refractory pulmonary edema or oliguria. Historically, it was thought that a pulmonary artery catheter may be favorable because central venous pressures are unreliable. Recently, echocardiography has been the favored method of monitoring for fluid status.
Pulmonary edema in preeclampsia may be due to left ventricular dysfunction secondary to high SVR, iatrogenic volume overload in the face of contracted intravascular space, decreased plasma colloid oncotic pressure, or pulmonary capillary membrane injury. Of note, in the event of respiratory compromise requiring intubation, it is important to note that patients often have laryngeal edema making intubation difficult. Advanced airway devices and a skilled anesthesiologist may be required.
Oliguria in preeclampsia is due to intravascular volume depletion (most common), relative volume overload with decreased left ventricular function secondary to high SVR, or renal arteriolar spasm. Echocardiographic assessment of cardiac function can help determine the cause of oliguria and course of treatment.
HELLP Syndrome—Preeclampsia can be complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. It is unclear if HELLP syndrome represents a separate clinical entity from preeclampia or is just a part of the spectrum of disease. Women with HELLP syndrome are generally older and multiparous and HELLP syndrome can occur in the absence of proteinuria or hypertension.
Laboratory evidence of HELLP syndrome includes abnormal peripheral smears (burr cells, schistocytes, echinocytes), hemolysis (elevated indirect bilirubin, LDH > 600, low haptoglobin), elevated liver transaminases (2× upper limit of normal), and thrombocytopenia (plt < 100k). Severe thrombocytopenia (plt < 30k) occurs rarely and these patients may require platelet transfusion for delivery.
In the absence of liver rupture, treatment of HELLP syndrome is generally supportive other than delivery. Serial monitoring of laboratory values and magnesium administration for seizure prophylaxis are recommended. Additionally, dexamethasone 10 mg intravenously every 12 hours can be administered to speed the process of laboratory value improvement in the setting of severe thrombocytopenia. Corticosteroids have not been shown to improve maternal morbidity or mortality.
In the event of liver rupture, operative exploration should be expedited as this is a surgical emergency. Exploration should not be delayed for imaging studies. The maternal mortality rate associated with HELLP syndrome has been estimated to be 1% with most mortality occurring in the setting of liver rupture.
Eclampsia—Eclampsia is defined as the presence of grand mal seizures in women with preeclampsia without a seizure disorder or other attributable cause of seizures. Eclampsia carries of maternal mortality rate of 1% to 2% and a fetal mortality rate of 10%. Onset of seizures is often preceded by symptoms including a severe unrelenting headache, nausea, or vomiting. Seizures are usually self-limited and medication is not usually required to break the seizure activity.
Treatment of eclampsia is standard magnesium administration with a 4 to 6 g bolus and then a continuous infusion of 2 g/h. Magnesium should be administered expeditiously in the setting of eclampsia, however, the purpose is to prevent recurrent seizure. Magnesium is superior to phenytoin and diazepam for preventing additional seizures.
Once seizure activity is controlled, delivery should be affected. In many cases, labor can be induced safely and a vaginal delivery can be achieved. Magnesium prophylaxis should be continued throughout delivery and for 24 hours postpartum.
Additional Critical Care Events—Disseminated intravascular coagulation, hypertensive encephalopathy, acute myocardial infarction, acute renal failure, intracranial hemorrhage, and acute aortic dissection can also be associated with hypertensive disorders in pregnancy. In each of these settings, a multidisciplinary approach with critical care, obstetrics, anesthesia and in certain cases other services is required to provide adequate care.
Acute Fatty Liver of Pregnancy
Essentials of diagnosis: hepatic dysfunction and microvesicular fatty infiltration of hepatocytes.
Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication of pregnancy with an incidence between 1:7000 and 1:16,000. It occurs late in pregnancy or immediately postpartum, often as fulminant liver failure with sudden onset coagulopathy and encephalopathy in women with no history of liver disease. Microvesicular fatty infiltration of hepatocytes is seen on microscopy.
Historically, AFLP was thought to be universally fatal, but early recognition, aggressive stabilization of the mother, and prompt delivery have improved the prognosis. Maternal and fetal mortality are currently estimated at approximately 15%.
The exact etiology of AFLP remains unknown. In many cases, either the mother or fetus is found to have an autosomal mutation that causes deficiency of the long-chain 3-hydroxyacyl coenzyme-A dehydrogenase (LCHAD), a fatty acid beta-oxidation enzyme. The association of this mutation with AFLP is strong enough that screening for the LCHAD mutation is recommended in the infants of affected mothers. Additional risk factors include nulliparity, multiple pregnancy, male fetus, and coexisting preeclampsia.
Symptoms or Signs—Patients often present with a history of 1 to 2 weeks of nausea, vomiting, anorexia, and malaise. On physical exam, patients are ill-appearing often with some degree of jaundice. Hypertension with or without proteinuria and transient diabetes insipidus with polydipsia and polyuria are also common.
In severe disease, ascites, progressive hepatic encephalopathy, hypoglycemia, coagulopathy, metabolic acidosis, and renal failure are also often seen. Intrauterine fetal demise occurs frequently, often prior to the diagnosis, likely due to hypoglycemia and uteroplacental insufficiency.
Laboratory Findings—Diagnosis of AFLP is suspected based on clinical presentation and dramatic laboratory changes (Table 60–3), but a definitive diagnosis cannot be made without a liver biopsy, confirming microvesicular fat infiltration of the hepatocytes.
Table 60–3Laboratory changes in acute fatty liver of pregnancy. |Favorite Table|Download (.pdf) Table 60–3Laboratory changes in acute fatty liver of pregnancy.
|Elevated WBC (> 20 K) ||Decreased Fibrinogen |
|Prolonged PT and aPTT ||Decreased Platelets |
|Elevated Ammonia ||Decreased Coagulation Factors |
|Elevated Uric Acid ||Decreased pH (acidosis) |
|Elevated BUN/Creatinine ||Hypoglycemia |
|Hyperglycemia (if associated with pancreatitis) ||Decreased Serum Albumin |
|Elevated Transaminases (< 2000 IU/L) || |
Care of a patient with suspected AFLP has 4 categories: diagnosis, stabilization, delivery, and support. During the diagnosis phase of management, intensive monitoring of the mother and the fetus are required. Because the fetal status can decline rapidly, if AFLP is suspected continuous external fetal monitoring should be applied until the diagnosis is ruled out or delivery is affected. Maternal hemodynamic and metabolic status should be monitored both clinically and with laboratory values.
The stabilization phase includes treatment of the complications of AFLP that are present. This includes establishing stable airway in an obtunded patient, normalizing intravascular volume, correcting electrolyte disturbances, treating hypoglycemia/hyperglycemia and correcting coagulation abnormalities with blood products. In certain cases, dialysis may be required for acute renal failure or desmopressin for diabetes insipidus.
Once the patient is stabilized, an expeditious delivery is recommended within 24 hours. The diagnosis of AFLP does not require a cesarean delivery. In fact, in the setting of significant coagulopathy, operative delivery may increase maternal morbidity and mortality. Regional anesthesia is often prohibited in cases of AFLP due to coagulopathy and thrombocytopenia. Care should be taken with medication choices if general anesthesia is required because certain medications can exacerbate liver failure.
Following delivery, care is supportive until the multisystem organ failure improves. This often requires ICU admission. Fluid balance, electrolyte status, and glycemic management are critical to survival. Blood glucose should be monitored hourly and electrolytes every 2 to 4 hours. Evidence of disseminated intravascular coagulation should be managed aggressively with blood products. Protein intake should be limited with the majority of caloric intake from glucose to decrease the nitrogenous waste. Colonic emptying should be facilitated with promotility agents to increase ammonia loss via stool. Neomycin 6 to 12 g or lactulose 20 to 30 g can also be administered daily to decrease colonic ammonia production. Occasionally, the liver damage from AFLP is so severe that transplantation is required.
Anaphylactoid Syndrome of Pregnancy/Amniotic Fluid Embolism
Essentials of diagnosis: hypotension, hypoxia, coagulopathy and frequently seizures/pulmonary edema/cardiac arrest.
Amniotic fluid embolism (AFE) is a rare but catastrophic complication of pregnancy. The incidence is unknown but is thought to be between 1:8000 and 1:30,000 pregnancies. An AFE is a foreign substance (amniotic fluid with fetal squamous cells) that is introduced into the maternal circulation which causes an acute cardiovascular and pulmonary collapse with associated coagulopathy.
AFE usually occurs during labor, delivery or the first 30 minutes postpartum. The classic presentation is an acute cardiopulmonary arrest in a previously healthy woman laboring or immediately postpartum. Seventy percent of cases occur during labor. Cardiac arrest is common and amniotic fluid emboli account for 5% to 10% of all maternal deaths in the United States. Fetal mortality is approximately 21% and fetal neurologic complications occur in more than half of infants delivered to mothers with an AFE.
Risk factors for amniotic fluid emboli include increased maternal age, uterine overdistension, cesarean delivery, uterine rupture, placental abruption, severe cervical lacerations, and maternal trauma. Links have been suggested between AFE and meconium stained amniotic fluid, augmented labor, and hypertonic contractions but these reports have not been validated.
Symptoms and Signs—The diagnosis of an AFE is made clinically with the spectrum of disease ranging from mild coagulopathy to sudden and complete cardiopulmonary collapse. Patients most often present with dyspnea, hypotension (100%), and hypoxia (93%). Coagulopathy (83%) and altered mental status (70%) are also common. Seizure activity occurs in approximately 33% of patients and significantly increases maternal morbidity and mortality. Constitutional symptoms (fever, chills, nausea, vomiting, and headache) are also present to varying degrees.
Laboratory Findings—Lab values are nonspecific and do not aid in the diagnosis of AFE. Evidence of coagulopathy without previous blood loss is suggestive and significant hemorrhage is often seen acutely. Fetal squamous cells in the maternal pulmonary circulation at the time of autopsy are diagnostic but cannot always be identified due to prolonged courses following the acute event.
AFE is a rare and unpredictable disorder of pregnancy. Treatment includes prompt initiation of basic and advanced cardiac life support. Continuous cardiac monitoring and pulse oximetry are required with invasive blood pressure monitoring. Coagulopathy must be managed promptly and aggressively with hemorrhage protocol combinations of packed red cells, fresh frozen plasma, cryoprecipitate, and platelets. In catastrophic cases where hemorrhage cannot be controlled, newer procoagulant agents should be used and a hysterectomy may be required. If an AFE is suspected before delivery, delivery should be prompt once the maternal condition is stabilized.
Essentials of diagnosis: heart failure in last month of pregnancy or within 5 months of delivery, no history or other identifiable cause, LV systolic dysfunction.
Peripartum cardiomyopathy (PPCM) occurs in about 1:2200 to 1:3200 pregnancies in the United States but is seen much more commonly globally. It is defined as heart failure in the last month of pregnancy or up to 5 months postpartum in the absence of known heart disease or another identifiable cause. It is characterized by left ventricular systolic dysfunction with an ejection fraction of < 45% or reduced fractional shortening.
Risk factors for peripartum cardiomyopathy include multiparity, black race, maternal age more than 30, hypertensive disorders of pregnancy, multiple gestation, long term tocolytic therapy (terbutaline), and maternal cocaine abuse. The exact etiology is unknown.
About half of patients will have complete resolution of symptoms after delivery with return of normal cardiac size and function. The remainder has continued dilation and often progressive heart failure. Future pregnancies are extremely high risk in women with a history of peripartum cardiomyopathy. In women without complete resolution of symptoms, future pregnancy mortality approaches 50%.
Symptoms and Signs—Patients present with symptoms of heart failure. Some of the initial nonspecific symptoms may be confusing due to the prevalence of these symptoms in normal pregnancy.
Imaging studies show enlargement of the cardiac silhouette and pulmonary edema. Echocardiography shows decreased universal contractility and left ventricular enlargement without hypertrophy. Diagnostic criteria used include: Left ventricular ejection fraction less than 45% and/or fractional shortening of less than 30% and left ventricular end systolic dimension greater than 2.7 cm/m2.
Laboratory Findings—Arterial blood gas shows hypoxemia with respiratory alkalosis. Urinalysis can show concentrated urine. CBC, serum chemistries and liver function tests should be unremarkable. Brain natriuretic peptide (BNP) levels typically increase 2 fold in healthy pregnancy and are usually elevated in heart failure, however limited data are available to support the use of this test in pregnancy. Elevated BNP has been observed in pregnant women with preeclampsia and other clinical conditions associated with volume overload.
Special Considerations—Systemic and pulmonary embolization can be seen more frequently than in other forms of cardiomyopathies.
Treatment of PPCM is similar to that for other types of heart failure. The goal in management is to improve cardiac function by reducing afterload and preload and increasing contractility. It is important to remember to avoid angiotensin inhibition, which is contraindicated in pregnancy.
Initial stabilization may require intravenous diuretics or inotropic support. Loop diuretics serve to decrease preload and relieve pulmonary congestion. Digoxin may improve myocardial contractility and facilitate rate control when atrial fibrillation is present. Hydralazine is the vasodilator of choice and can be used to reduce afterload before delivery and angiotensin-converting enzyme inhibitors can be used postpartum. Beta blockade has also been shown to improve cardiac function and survival in chronic heart failure but should not be used in acute decompensated heart failure. Patients with acute decompensated heart failure with hypotension or persistent pulmonary edema despite initial measures may benefit from intravenous inotropic support with Dobutamine or Milrinone. An intra-aortic balloon pump, extracorporeal membrane oxygenation, and LV assist devices have been used successfully as a bridge for recovery or transplantation in patients with PPCM and should be considered in rapidly deteriorating patients who are not responding to medical therapy, including inotropic medications.
Anticoagulation with heparin should be considered if EF is significantly reduced, that is, less than 35% due to the high risk of thrombus formation and thromboembolism in the context of pregnancy-related hypercoaguabllity and stasis due to LV dysfunction.
Early delivery may be necessary if persistent hemodynamic instability is present, but if the mother is stabilized the goal is delivery at term. Cesarean delivery is reserved for obstetric indications. Early pain control is a key in patients with peripartum cardiomyopathy during labor as pain increases cardiac work and causes tachycardia. A carefully dosed epidural that provides adequate pain control and avoids hypotension is vital.