Pre-eclampsia, Eclampsia and Pregnancy-Induced Hypertension

I. What Every Physician Needs to Know.

Pre-eclampsia is a syndrome of unknown etiology complicating human pregnancy. It is characterized by the new onset of hypertension and proteinuria after 20 weeks gestation and may involve multiple organ systems. While severe pre-eclampsia and eclampsia are uncommon, they can be catastrophic and are one of the leading causes of maternal death and contribute significantly to the rate of premature birth. Between 50,000 and 75,000 (14%) of worldwide maternal deaths per year are attributable to pre-eclampsia and eclampsia. Delivery of the fetus and placenta is the definitive cure for the disease. An obstetrician should be the primary clinician managing a pre-eclamptic or eclamptic patient, as these are obstetric diseases.

II. Diagnostic Confirmation: Are You Sure Your Patient Has Pre-eclampsia, Eclampsia or Gestational Hypertension?

Pre-eclampsia is defined as new onset hypertension and proteinuria after 20 weeks gestation. An elevation of blood pressure (140 / 90 millimeters mercurgy [mmHg] or greater) and proteinuria (300 milligrams [mg] / 24 hours or greater) in a woman with previously normal blood pressure meets the clinical diagnostic criteria. To meet the definition of pre-eclampsia the blood pressure must be elevated on two separate occasions at least 6 hours apart but within a 7-day period.

Eclampsia is defined as development of generalized tonic-clonic seizure not due to another cause in a woman with pre-eclampsia.

Gestational hypertension is a diagnosis and is defined as new onset elevation of blood pressure (140/90 mmHg or greater) without proteinuria after 20 weeks gestation (previously known as pregnancy-induced hypertension). If the hypertension does not progress to pre-eclampsia at the time of delivery and resolve by 12 weeks postpartum, it is then termed transient hypertension. If the hypertension persists beyond 12 weeks postpartum then it is determined to be chronic hypertension.

A. History part I: Pattern Recognition

Early diagnosis of pre-eclampsia is crucial as it allows for appropriate management that will decrease the progression to pre-eclampsia with severe features and eclampsia, and as a result, reduce maternal and fetal morbidity and mortality. Thus, obstetricians should always have a high index of suspicion for the diagnosis of pre-eclampsia if a parturient at term with normal baseline blood pressures in early pregnancy presents to her prenatal care visit with new onset elevation of blood pressure at or above 140 / 90 mmHg. It is important that the history and physical exam be specific for the signs and symptoms of pre-eclampsia.

Although the parturient may be asymptomatic, typical signs and symptoms of pre-eclampsia include: excessive weight gain (more than 5 pounds in one week), increasing non-dependent edema (hand and facial edema), blurred vision, and persistent headache. However, pre-eclampsia could be linked to some non-specific symptoms, including malaise, nausea and vomiting, epigastric or right upper quadrant pain.

The majority of cases of pre-eclampsia are seen at or beyond 37 weeks gestation (late onset) but 10% occur at a gestational age of less than 34 weeks (early onset). There is a recent body of evidence supporting the concept that there are distinct etiologies for early onset pre-eclampsia and late onset pre-eclampsia. It is postulated that early onset pre-eclampsia is a placentally-mediated fetal disorder resulting in abnormal uterine artery Doppler flow and fetal growth restriction, leading to poor maternal and fetal outcomes. In contrast, late onset pre-eclampsia is a maternal disorder resulting from underlying maternal constitutional status and is often associated with a normal placenta, normal fetal growth, and thus, better maternal and neonatal outcomes.

It is important to note that pre-eclampsia can manifest as a syndrome (including hypertension and proteinuria with or without maternal multi-system disorder and/or fetal growth restrictive disorder). Pre-eclampsia is further divided into the categories of pre-eclampsia without severe features and pre-eclampsia with severe features. Pre-eclampsia with severe features is diagnosed if any one of the following parameters is present:

Elevation of systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher while the patient is on bed rest on two separate occasions at least 4 hours apart
Persistent new-onset headache or other symptoms of cerebral or visual disturbances
Pulmonary edema
Epigastric or right upper quadrant pain which is severe, cannot be attributed to another diagnosis, and is refractory to medication
Thrombocytopenia (platelet count less than 100,000 cells/microliter)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevated greater than two times higher than baseline
Serum creatinine greater than 1.1 milligrams/deciliter (mg/dL) or two times higher than baseline

Pre-eclampsia is considered to be without severe features in the absence of the above parameters. Unfortunately, what appears to be pre-eclampsia without severe features can progress to pre-eclampsia with severe features quite rapidly, and as such, the patient must be monitored carefully for disease progression.

Another variant of severe pre-eclampsia is HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. HELLP syndrome is noted for its highly variable presentation. Approximately 12 to 18% of women with HELLP syndrome have normal range blood pressures and 13% do not develop proteinuria. Thirty percent of women first develop HELLP syndrome in the postpartum period, 52% at a premature gestational age, and 18% with a term gestation. Though HELLP syndrome can be extremely variable, the more common presenting symptoms include right upper quadrant or epigastric pain, nausea and vomiting, vague constitutional symptoms, or malaise mimicking a viral syndrome. HELLP syndrome can be diagnosed with findings of increased lactate dehydrogenase (LDH) level, elevated ALT and AST, elevated indirect bilirubin, and low platelet counts.

B. History Part 2: Prevalence

The exact incidence of pre-eclampsia is unclear, although it is reported to complicate approximately 5-8% of all pregnancies. Pre-eclampsia is more commonly encountered in a first pregnancy. Other maternal risk factors for development of pre-eclampsia include chronic hypertension, renal disease, obesity, diabetes mellitus, thrombophilia, vascular and connective tissue disorders, extremes of maternal age (less than 15 and greater 35 years of age), and African American ethnicity. A family history of pre-eclampsia, a prior pregnancy complicated by pre-eclampsia, gestational hypertension or fetal growth restriction of unknown etiology, index pregnancy with multifetal gestation or molar pregnancy, contribute to the risk of development of pre-eclampsia. Very few factors, namely tobacco use and placenta previa, decrease the risk of pre-eclampsia.

Studies have suggested a genetic component to the development of pre-eclampsia, with close relatives (daughters and sisters) of women with pre-eclampsia more likely to develop the disease themselves. Twin studies also indicate a positive correlation between siblings. Furthermore, it appears that women with thrombophilia may be predisposed to the development of pre-eclampsia. Over 100 genes have been studied for their connection to pre-eclampsia. However, as pre-eclampsia is an extremely complex disease, it is unlikely that any one gene plays a significant role in determining susceptibility.

C. Competing diagnoses that can mimic Pre-eclampsia and Eclampsia

Several conditions, including acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, systemic lupus erythematosus with lupus nephritis, systemic viral hepatitis, and other viral illnesses, may mimic pre-eclampsia. Rarely, pre-eclampsia is superimposed atop one of these illnesses in a patient, making the diagnosis even more complex and difficult.

Many causes of seizures, including epilepsy, encephalitis, meningitis, cerebral tumor, and cerebral venous thrombosis during late pregnancy and the peurperium can mimic eclampsia.

D. Physical Examination Findings of Pre-eclampsia and Eclampsia

On physical examination, blood pressure is noted to be elevated at 140 / 90 mmHg or above on two separate occasions at least 4 hours apart. The parturient may develop excessive weight gain over a short period of time (more than 5 pounds in a week) and may have sudden increase in edema in nondependent areas (facial, periorbital, and hand edema). Abdominal examination may be significant for right upper quadrant abdominal pain or epigastric pain. A lagging fundal height is suspicious for fetal growth restriction or oligohydramnios. Development of apprehension, excitability, or hyperreflexia is concerning for an increased risk of eclamptic seizure.

Patients with severe preeclampsia may display end-organ effects. They may complain of neurologic symptoms (headache, visual disturbances, altered mental status, blindness due to cortical blindness or retinal vasculature damage), symptoms of hepatic involvement (epigastric or right upper quadrant abdominal pain), symptoms of pulmonary edema (shortness of breath), symptoms of renal insufficiency (oliguria), or evidence of hemolytic anemia (weakness or malaise).

E. What diagnostic tests should be performed?

The first diagnostic test would be blood pressure measurement. To diagnose hypertension in pregnancy, an elevated reading of 140/90 mm Hg or greater must be obtained on two separate occasions at least 4 hours apart but within a period of 7 days.

Caution must be taken to measure the blood pressure appropriately. A properly-sized cuff must be used on the right arm at the level of the heart on a seated patient (in an ambulatory setting) or in a semi-reclining position (in a hospital setting). Of note, it is not recommended to take the blood pressure in the upper arm of a woman lying in a left lateral position because the blood pressure would then be falsely lowered.The patient should rest quietly for 10 minutes and abstain from tobacco or caffeine for 30 minutes prior to having the blood pressure taken. The same technique should be used on all measurements to ensure consistency of readings. Diastolic pressure should be measured with the Korotkoff V sound whenever possible. If it is absent, this should be noted and the Korotkoff IV sound may be substituted, although the two sounds may be as much as 10 mmHg apart. Automatic devices can be used as long as they are able to record the Korotkoff V sound, although a mercury sphygmomanometer is the more accurate device.

The other required diagnostic test is the collection of all urine during a 24-hour period for determination of the degree of proteinuria. The diagnostic threshold for preeclampsia is 300 mg of protein in a 24-hour urine collection. A spot protein/creatinine ratio cut-off level of 0.3 mg/dL can be used instead of the 24-hour urine collection for protein. Urine dipstick analysis has low accuracy and is not recommended for determination of proteinuria; if there is no other available alternative then a cut-off value of 1+ indicated proteinuria diagnostic of preeclampsia.

These diagnostic criteria (hypertension and proteinuria) would apply to the majority of women with pre-eclampsia. However, some women have developed pre-eclampsia and eclampsia without either hypertension or proteinuria, although they may present with other signs and symptoms or laboratory abnormalities of pre-eclampsia. For example, a parturient with pre-eclampsia might not have elevation of blood pressure at the onset but she may present with manifestations of a capillary leak (such as proteinuria, ascites, or pulmonary edema) or abnormalities in laboratory values suggestive of multiorgan dysfunction. Conversely, the absence of proteinuria should not negate the diagnosis of pre-eclampsia syndrome, particularly in the setting of gestational hypertension with persistent symptoms and laboratory abnormalities. Recently, in the absence of proteinuria, new-onset hypertension along with these manifestations (thrombocytopenia, elevated liver enzymes, elevated serum creatinine, cerebral symptoms, and pulmonary edema) have been recognized as pre-eclampsia with severe features.

1. What laboratory studies should be ordered to help establish the diagnosis? How should the results be interpreted?

New-onset hypertension in a pregnant woman should be evaluated with: complete blood count (CBC), serum ALT and AST, serum creatinine, serum uric acid levels, and a 24-hour urine collection for protein. If HELLP syndrome is suspected, the addition of a peripheral smear, serum lactate dehydrogenase (LDH) and indirect bilirubin is recommended. A coagulation profile consisting of a prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen is not indicated unless the platelet count is less than 100,000 cells/microliteror if there is evidence of bleeding.

A finding of at least 300 mg of protein in a 24-hour urine collection fulfills the laboratory criteria for the diagnosis of pre-eclampsia. Current literature reports variance in threshold levels to indicate end-organ involvement in pre-eclampsia with severe features or HELLP syndrome. In general, the accepted values are as follows:

Hematologic changes:

Abnormal peripheral blood smear (schistocytes, burr cells, or echinocytes)
Indirect bilirubin >1.2 mg/dL
Platelet count <100,000 cells/ microliter
Low serum haptoglobin
Disseminated intravascular coagulation (DIC): thrombocytopenia, plasma fibrinogen < 300 mg/dL, fibrin split products above 40 mg/mL.
LDH >600 international units/liter (IU/L)

Renal function abnormalities:

Serum creatinine >1.1 mg/dL or twice of her baseline serum creatinine

Hepatic function abnormalities:

Serum AST and ALT > 72 IU/L

Of note, massive proteinuria of >5 grams/ 24 hours is no longer a diagnostic criteria for preeclampsia with severe features because the severe degree of proteinuria has recently been found not to be associated with worse maternal and neonatal outcomes.

2. What imaging studies should be ordered to help establish the diagnosis? How should the results be interpreted?

Ultrasound examination to evaluate fetal growth and amniotic fluid volume as well as a non-stress test (NST) to evaluate fetal well-being are necessary. If the diagnosis of fetal growth restriction is made, Doppler ultrasound evaluation of the umbilical artery should be performed to rule out uteroplacental insufficiency.

In certain situations after an eclamptic seizure, maternal imaging may include computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the head. These studies may show posterior reversible encephalopathy syndrome in women with eclampsia. In approximately 50% of cases of eclampsia, CT and MRI can show edema and infarction in the parieto-occipal subcortical white matter and adjacent gray matter. Cerebral imaging findings in eclampsia are similar to those seen in hypertensive encephalopathy.

Imaging is unnecessary to make the diagnosis in most eclamptic women. Indications for cerebral imaging include focal neurological deficits or prolonged coma in which other treatable processes (hemorrhage or abnormalities requiring medical or surgical intervention) must be excluded. Women with atypical presentation of eclampsia, either before 20 weeks or greater than 48 hours after delivery, or with eclampsia refractory to medical therapy with magnesium sulfate may also benefit from imaging to assist in diagnosis. Unfortunately there are no pathognomonic imaging findings for eclampsia.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Coagulation profile is not useful unless the platelet count is less than 100,000 cells/microliter or there is evidence of bleeding.
Although more convenient, a urine dipstick is not reliable in the diagnosis of proteinuria and should not be used for diagnosis when other methods are available.
An elevation in hematocrit and a high serum uric acid increase the suspicion for pre-eclampsia but should not be used to diagnose pre-eclampsia.
There are no pathognomonic abnormalities in electroencephalogram (EEG) of eclamptic women, despite abnormalities in the majority of patients.
Lumbar puncture has no role in the diagnosis or management of eclampsia.
There are no pathognomonic CT or MRI findings in eclampsia and imaging is not necessary for diagnosis or management except in the setting of atypical eclampsia, eclampsia refractory to magnesium sulfate therapy, or presence of focal neurological deficit or prolonged coma.
Repeating 24-hour urine collection for proteinuria is not required after the diagnosis of preeclampsia is made as severity of proteinuria is no longer a criteria for severe features of preeclampsia.

III. Default Management.

The goal of management of the pre-eclamptic patient is to expedite delivery of the fetus (as the placenta is the proposed source of the disease) without incurring significant maternal or fetal/neonatal morbidity, with the expectation of returning the mother to her baseline health after birth.

Gestational age and the severity of disease both impact management of a woman with pre-eclampsia. A balance between maternal risks from the disease process while continuing the pregnancy and fetal risks of lung immaturity must be reached as delivery is the only definitive cure for pre-eclampsia. An initial in-patient evaluation to determine the severity of the disease process is indicated. The general goals of management include blood pressure control and prevention of seizures in severe disease, administration of corticosteroids for gestation at less than 37 weeks (in anticipation of the risk for premature delivery), and close monitoring of maternal and fetal status for progression to severe disease.

A. Immediate management.

Until the severity of illness is determined and fetal well-being is established, in-patient evaluation of the pre-eclamptic patient is recommended. Initial evaluation should include the following:

Fetal assessment:

Fetal non-stress testing to determine fetal well-being
Ultrasound evaluation for fetal growth, including amniotic fluid volume examination
Doppler studies of the umbilical artery if fetal growth restriction is detected

Maternal assessment:

History and physical examination with specific focus on evidence of end-organ involvement
Serial blood pressure determination
24-hour urine collection for protein or protein and creatinine ratio
Blood work: CBC with platelet count, AST, ALT and creatinine level
LDH, indirect bilirubin, haptoglobin, and peripheral smear are added if HELLP syndrome is suspected

Maternal and fetal assessments are performed to determine the severity of the disease process and end-organ involvement, which would classify her as having preeclampsia with severe features. Management plan would depend on whether patient have the severe features of preeclampsia.

After this initial evaluation, if the patient met the diagnosis of either gestational hypertension or preeclampsia, proceeding toward delivery is indicated if patient is at gestational age of 37 weeks or beyond. However, delivery is also recommended if patient is at 34 weeks and beyond but have the following complications:

Rupture of the amniotic membranes
Progressing into active labor
Abnormal fetal testing (if biophysical profile score is persistently at 6/10 or less)
Fetal growth restriction at less than the 5^thpercentile for gestational age
Suspected placental abruption
Presence of severe features of preeclampsia

Management of pre-eclampsia without severe features and mild gestational hypertension at less than 37 weeks

Pre-eclampsia without severe features and mild gestational hypertension before 37 weeks is typically managed expectantly to allow in-utero fetal maturation. Corticosteroids are administered to enhance fetal lung maturity in patients who develop pre-eclampsia prior to 37 weeks. After an initial period of evaluation in the hospital, outpatient management might be considered for the stable and compliant parturient at a preterm gestation (< 37 weeks) if fetal and maternal evaluations are reassuring and consistent with either mild gestational hypertension or pre-eclampsia without severe features.

Bed rest is not necessary and can increase risk of thromboembolism and muscle atrophy, but reduced activity may be beneficial in the management of pre-eclampsia without severe features and mild gestational hypertension. There are no dietary restrictions regarding fluid or sodium intake. Outpatient management must maintain high levels of surveillance as close observation may detect early signs of disease progression and of note, women with preeclampsia without severe features can progress into severe preeclampsia in days. Re-hospitalization is indicated if there is evidence of worsening maternal or fetal status.

During outpatient management for preeclampsia without severe features, maternal and fetal status are monitored. Patient is instructed on daily fetal movement count. She is to return to the office for twice weekly blood pressures evaluation and NST, weekly evaluation of amniotic fluid volume and weekly blood work (including CBC with platelet count, AST, ALT, and serum creatinine). For patient with mild gestational hypertension, she will have weekly office visit for blood pressure evaluation, NST and amniotic fluid index, and blood work (including CBC with platelet count, AST, ALT, and serum creatinine). She will also need her blood pressure re-evaluated another time during the week, either at home or at another office visit. In addition, woman with gestational hypertension will require evaluation for proteinuria at each clinic visit until she develops proteinuria that is diagnostic of preeclampsia. Subsequently, further repeat evaluation of proteinuria is not indicated since worsening proteinuria is not associated with adverse maternal and fetal outcomes.

Ultrasound examination for evaluation of interval fetal growth is performed every 3 weeks for women with mild gestational hypertension or preeclampsia without severe features.

Patients with pre-eclampsia without severe features can be expectantly managed until term or spontaneous labor commences. The prospective randomized HYPITAT trial involving 756 women with gestational hypertension or mild pre-eclampsia suggested delivery is more advantageous than expectant management after 36 weeks. Therefore, development of pre-eclampsia in women after 37 weeks gestation should lead to induction of labor regardless of cervical status as there is an increased risk of placental abruption and progression to severe disease. Vaginal delivery should be attempted whenever possible unless a contraindication is present.

Management of pre-eclampsia with severe features and severe gestational hypertension

Parturients who meet diagnostic criteria for pre-eclampsia with severe features at 34 weeks or beyond should be delivered, as risks of expectant management outweigh the risks of delivery. Difficulties in management arise in women at gestations less than 34 weeks with severe features. Definitive cure for this disease requires immediate delivery, which will result in significant neonatal morbidity and mortality due to premature birth; however, prolonging the pregnancy to allow in utero fetal maturation could result in fetal demise and further jeopardize maternal health.

Recent studies concluded that for a carefully selected group of women at gestational ages between 24 0/7 and 33 6/7 weeks of gestation with pre-eclampsia with severe features, expectant management might be considered and can improve neonatal outcomes. Candidates for in-hospital expectant management are those who were diagnosed with pre-eclampsia with severe features based on severe range blood pressures that are well controlled with medication. The presence of other signs of maternal end-organ dysfunction or non-reassuring fetal status preclude expectant management.

Therefore, pre-eclamptic women with severe features should be delivered promptly regardless of gestational age if any of the following are present:

Eclampsia
Nonreassuring fetal status
Severe range blood pressures – not controlled by appropriate management with anti-hypertensive medication
Persistent cerebral symptoms (severe headache) and visual disturbances
Placental abruption
Non-viable fetus
Fetal demise
Development of HELLP syndrome
Pulmonary edema
Presence of disseminated intravascular coagulopathy
Subcapsular liver hematoma

Pre-eclamptic women at less than 34 weeks gestation with the following severe features: HELLP or partial HELLP syndrome, fetal growth restriction, oligohydramnios, reversed-end diastolic flow of the umbilical artery by Doppler studies, and significant renal insufficiency can be candidates for expectant management for 48 hours to achieve the benefit of corticosteroid for fetal lung maturation.

Other pre-eclamptic women at less than 34 weeks gestation with severe features based on severe range blood pressures (controlled on medication) can be expectantly managed.

During the initial 24-hour observation in the labor and delivery unit, blood pressure control is optimized, magnesium sulfate for seizure prophylaxis is started, and corticosteroids are administered. If maternal and fetal status remain reassuring after the initial 24-hour observation, magnesium sulfate is discontinued and the parturient is transferred to the antepartum high risk floor for expectant management until either delivery at 34 weeks gestation or worsening of maternal and/or fetal status. Anti-hypertensive medication is continued if indicated.

These parturients should only be managed expectantly at a tertiary care center after detailed counseling and only if they fully understand the risks and benefits associated with their decisions.

Subsequent in-hospital expectant management and monitoring should include the following:

Careful and frequent evaluation for symptoms concerning for risk of eclampsia (headache, changes to vision, and/or epigastric pain) at least every 8 hours
Vital signs (in particular, blood pressure measurement), fluid intake and urine output should be charted at least every 8 hours
Daily serum creatinine, AST, ALT, LDH, and platelet count; possibly every other day in asymptomatic patients with stable laboratory values.
Daily fetal movement count
Daily non-stress test and uterine contraction monitoring with an increase in frequency as indicated by maternal and fetal status
Twice weekly biophysical profile
Ultrasound evaluation of fetal size every 2 weeks
Doppler studies of the umbilical artery every 2 weeks in situation of fetal growth restriction.

Management of eclampsia and seizure prophylaxis

During an eclamptic seizure, maternal stabilization is the priority with the airway, breathing circulation (ABCs) of airway, breathing and circulation being the first step in management. Magnesium should be initiated at the first opportunity with a loading dose of 4-6 grams (g) intravenously (IV) over 5-10 minutes followed by infusion of 1-2 g/hour. If magnesium was already being infused, consider an additional 2 g bolus over several minutes. If seizures are recurrent, an additional 2 g bolus may be administered. Total dose of no more than 8 g should be administered. A slow 100 mg IV dose of thiopental sodium or 1-10 mg of diazepam may be necessary for seizures refractory to standard magnesium sulfate. CT imaging of the brain is indicated in eclamptic women with recurrent seizures despite therapeutic magnesium sulfate level.

Once the mother is stabilized and the fetal heart rate recovers, plans are made to expedite delivery. Cesarean delivery is reserved for usual obstetrical indications as vaginal delivery may be achieved in at least half of eclamptic patients. Some experts recommend cesarean delivery for women at gestational age less than 30 – 32 weeks with an unfavorable cervix as the chance for successful vaginal delivery with labor induction is low.

Up to 1/3 of seizures occur postpartum, typically within 24-48 hours of delivery. For this reason, magnesium prophylaxis is continued for at least 24 hours after delivery or until there is evidence of disease resolution, whichever is longer. The most reliable clinical indication of disease resolution is a spontaneous, brisk diuresis.

Prophylactic magnesium sulfate is only recommended for patients with pre-eclampsia with severe features. However, it is a well-known fact that certain signs and symptoms (severe headache, clonus, altered mental status, right upper quadrant pain, visual changes) herald impending eclampsia, and thus would influence the physician’s decision to start on magnesium sulfate prophylaxis. Furthermore, progression from mild to severe pre-eclampsia is rapid and without warning, therefore, close surveillance of maternal status is recommended to allow for prompt initiation of magnesium sulfate if there is evidence of disease progression.

Magnesium sulfate administration is not without risk. Evidence of magnesium toxicity includes:

loss of deep-tendon reflexes
respiratory depression
blurred vision
cardiotoxicity

It is important to note that toxicity can occur at therapeutic levels of serum magnesium, therefore frequent clinical assessment of the patient on continuous infusion of magnesium sulfate is mandatory. Treatment of magnesium toxicity is 1 g of 10% calcium gluconate given intravenously. Furthermore, as magnesium freely crosses the placenta, a newborn resuscitation team should be present at all deliveries in which the mother received magnesium sulfate.

Treatment of severe range blood pressure

Antihypertensive medications are recommended if blood pressure becomes severe (systolic blood pressure >160 mm Hg or diastolic blood pressure > 110 mm Hg). The goal of therapy is to prevent maternal cerebral injury and infarction while maintaining adequate uteroplacental blood flow. In the United States, cerebrovascular accident (CVA) is cited as the most common cause of maternal mortality from pre-eclampsia. Adequate blood pressure control may prevent CVA in some women. The target blood pressure in these pregnant women is 140 – 150 / 90-100 mm Hg to avoid reduction of uterine blood flow, which can lead to uteroplacental insufficiency.

The first-line treatment of severe hypertension in pregnant and postpartum women should be with either IV labetalol or hydralazine. Hydralazine carries a stronger risk of hypotension (systolic blood pressure < 90mm Hg) while labetalol can be associated with neonatal bradycardia. Furthermore, labetalol should not be used in women with asthma or heart failure. Neither agent appears to impact umbilical blood flow significantly, and maternal and neonatal outcomes are comparable between the two. In the event that intravenous access is unavailable in a hypertensive emergency, 200 mg of labetalol can be given orally, and a second dose given in 30 minutes. While magnesium sulfate is the recommended agent for seizure prophylaxis and treatment, it is not recommended for the treatment of hypertension.

In the rare instance of a patient failing to respond to IV hydralazine or labetalol, second-line agents such as labetalol or nicardipine via infusion pump may be attempted with consultation from a critical care specialist, maternal-fetal medicine specialist, or anesthesiologist. Rarely, these agents can cause changes in umbilical artery blood flow. In a hypertensive emergency when there is inadequate response to any of these agents, sodium nitroprusside should be considered. Because of concerns about cyanide and thiocyanate toxicity in both mother and fetus/neonate as well as risk of increased intracranial pressure and cerebral edema in the mother, sodium nitroprusside should be used for the shortest possible duration and indicated only for extreme hypertensive emergencies.

Regional anesthesia and pre-eclampsia

The intravascular volume depletion of pre-eclampsia can result in hypotension after administration of regional anesthesia. These women may benefit from epidural anesthesia or newer combined techniques which achieve a regional block in slow increments. A skillful anesthesiologist will administer regional anesthesia to a pre-eclamptic patient who has a normal coagulation profile, good IV access, and who can tolerate pre-block hydration if a reproducible means of evaluating blood pressure is available.

Fluid management

Despite peripheral edema, the eclamptic patient is intravascularly volume depleted, and as such, diuretics should be avoided. Aggressive volume replacement or post-partum mobilization of extravascular fluid may precipitate pulmonary edema. Patients should therefore be volume restricted until spontaneous postpartum diuresis occurs. Total fluid input should be limited to 80 milliliters/hour or 1 milliliters/kilogram/hour.

Strict fluid input and output should be monitored, especially in the immediate postpartum period. Up to 6 hours of oliguria following delivery is expected at times and thus should be observed instead of overcorrected. A significant increase in urine output is also an important indicator of disease resolution, so hourly urine output should be closely monitored as a sign that maternal conditions are improving.

B. Physical Examination Tips to Guide Management.

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C. Laboratory Tests to Monitor Response To, and Adjustments in Management.

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D. Long-term management.

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E. Common Pitfalls and Side-Effects of Management.

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IV. Management with Co-Morbities.

Management of pre-eclampsia with other co-morbidities should be individualized with input from experts of the different sub-specialties and/or a maternal-fetal medicine specialist.

A. Renal Insufficiency.

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B. Liver Insufficiency.

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C. Systolic and Diastolic Heart Failure.

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D. Coronary Artery Disease or Peripheral Vascular Disease.

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E. Diabetes or other Endocrine issues.

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F. Malignancy.

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G. Immunosuppression (HIV, chronic steroids, etc).

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H. Primary Lung Disease (COPD, Asthma, ILD).

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I. Gastrointestinal or Nutrition Issues.

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J. Hematologic or Coagulation Issues.

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K. Dementia or Psychiatric Illness/Treatment.

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V. Transition of Care.

A. Sign-out considerations While Hospitalized.

The maternal and fetal status of every patient with pre-eclampsia with severe features who is being expectantly managed needs to be updated at each sign-out. In specific, any laboratory updates, results of daily antenatal testing and ultrasound examination, blood pressure measurements, other changes in physical examination, and development of symptoms suggestive of elevated risk of eclampsia should be conveyed to the in-coming team members. Pending laboratory values to evaluate progression of disease must be signed out for follow-up.

If there is any change in maternal status (e.g. significant rise in blood pressure measurement), all laboratory tests and fetal monitoring testing must be repeated to rule out worsening of disease process (even if these tests were recently performed).
If there is suspicion of disease progression, transferring the patient to the labor and delivery unit is required for continuous fetal monitoring and closer observation of maternal status with evaluation for possible delivery.
The medical team must be ready for the potential of rapid deterioration of maternal and fetal condition.
The immediate availability of anesthesiology, neonatology, operating room staff, and obstetrician is mandatory.

B. Anticipated Length of Stay.

It is anticipated that the patient with pre-eclampsia with severe features will remain hospitalized until after delivery at 34 weeks, or earlier in cases with evidence of progression of the disease process.

C. When is the Patient Ready for Discharge?

Postpartum management

Pre-eclampsia should resolve following delivery, but elevated blood pressures may persist postpartum. Recently, it is recommended that pre-eclamptic women have their blood pressures monitored for at least 72 hours after delivery either in the hospital or similarly at an outpatient setting. Follow-up evaluation is indicated at 7-10 days after delivery with earlier visit if patient develops symptoms. Documentation of liver function tests and platelet counts trending toward normal must occur prior to discharge.

If elevated liver enzymes, thrombocytopenia, and renal insufficiency persist for more than 72 hours postpartum, hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) must be considered.

Due to spontaneous resolution of the disease process after delivery, in cases of pre-eclampsia that are not complicated by (previously undiagnosed) chronic hypertension, it is expected that the blood pressure will normalize by 12 weeks postpartum. A patient discharged on antihypertensive medication should be advised to frequently monitor blood pressures at home, and adjustments or discontinuation of anti-hypertensive medication should be made as indicated.

Eclampsia can occur up to 6 weeks postpartum, and pre-eclamptic women who delivered are at risk for recurrent pre-eclampsia within the first 4 weeks postpartum. Therefore, women should be counseled on the above risks and advised on the signs and symptoms of pre-eclampsia prior to hospital discharge.

D. Arranging for Clinic Follow-up.

In patients discharged on antihypertensive medication, follow-up should occur no later than 1 week after discharge for revaluation of blood pressure and adjustment or discontinuation of anti-hypertensive medications as indicated. Patients should also be evaluated for signs and symptoms of recurrent pre-eclampsia. Laboratory evaluation of tests that were still abnormal at hospital discharge are repeated if indicated during the post-partum visit.

Gestational hypertensive women with persistent elevation of blood pressures at the 6 week postpartum visit should return at 12 weeks. The diagnosis of transient hypertension is made if blood pressures normalize by then; otherwise the diagnosis of chronic hypertension should be made and the patient appropriately referred for further evaluation and treatment.

1. When should clinic follow up be arranged and with whom.

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2. What tests should be conducted prior to discharge to enable best clinic first visit.

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3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

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E. Placement Considerations.

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F. Prognosis and Patient Counseling.

Approximately 10% of women who experience pre-eclampsia will have disease recurrence in a subsequent pregnancy. This risk increases to 20% if the patient had pre-eclampsia with severe features, HELLP syndrome, or eclampsia. The recurrence of HELLP syndrome is 5% while recurrence of eclampsia is 2%. The risk of disease recurrence increases in proportion to how early in pregnancy the initial disease developed, with a risk of pre-eclampsia recurrence as high as 40% in women who presented with disease prior to 30 weeks’ gestation. Daily low-dose aspirin therapy (60-100 mg daily) has been shown in some studies to decrease the risk of pre-eclampsia among women who are at increased risk of developing the disease.

Endothelial damage is a key feature of pre-eclampsia and contributes to future cardiovascular disease. Thus, women with pre-eclampsia should be counseled of a 4-fold increased risk of developing hypertension and a 2-fold elevated risk of ischemic heart disease, venous thromboembolism, and stroke. Recurrent pre-eclampsia and pre-eclampsia prior to 36 weeks’ gestational age put women at even greater risk for subsequent development of hypertension later in life.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

N/A

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