Perspective

Preeclampsia is a disease of pregnancy characterized by a sustained elevation in blood pressure (sitting blood pressure of ≥140 mm Hg systolic or ≥90 mm Hg diastolic) and proteinuria (≥1+ in a random urine sample or 300 mg in a 24-hour urine sample) occurring after the 20th week of gestation. Edema is common in patients with preeclampsia but is not necessary for the diagnosis. Eclampsia is defined by seizures, usually in the setting of preeclampsia. Seizures are rare without underlying preeclampsia. Although preeclampsia develops most commonly after the 20th week of pregnancy, it may occur in the postpartum period, usually within the first 24 to 48 hours, but delayed manifestations of 2 weeks or longer have been reported.

Epidemiology

Preeclampsia complicates 5% to 11% of pregnancies in the United States. The rate is higher in developing nations. This disease accounts for a significant percentage of both maternal and fetal mortality. Fetal complications such as prematurity and low birth weight are common, with death occurring in 129 of every 1000 cases. Maternal complications are common in both eclampsia and severe preeclampsia, including HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (11%), placental abruption (10%), disseminated intravascular coagulation (DIC) (6%), neurologic deficits (6%), aspiration pneumonia (6%), pulmonary edema (5%), renal failure (4%), and death (1%).

First pregnancies are at greatest risk. Other risk factors include extremes of reproductive age, more than 10 years between pregnancies, multiple gestations, molar pregnancies, previous or family history of preeclampsia, underlying diseases (hypertension, diabetes, autoimmune or renal diseases, obesity), and thrombophilia (e.g., antiphospholipid syndrome, factor V Leiden deficiency, activated protein C resistance).¹

Pathophysiology

Preeclampsia is a multisystem disorder of gestation. Its exact cause is unclear and several mechanisms have been implicated. The disease is thought to originate within the placenta, which for reasons that remain obscure, has inappropriately decreased perfusion. Hypoperfusion and multiorgan effects ensue in some patients as a result of decreased intravascular volume and endothelial vascular leakage causing increased interstitial volume, interstitial protein leakage, and vasoconstriction.² Preeclampsia affects nearly every organ system.

Severe preeclampsia is characterized by hypertension secondary to increased peripheral resistance. However, the profound elevation in blood pressure is the result rather than the cause of the underlying pathophysiology. Effects on the liver include edema, hepatocellular necrosis, and periportal and subcapsular hematomas. Decreased renal flow with high perfusion pressure can cause glomerular and tubular injury resulting in proteinuria or, worse, renal failure. Cerebral vasospasm leads to edema, microinfarction, and hemorrhage. Patients experience a variant of chronic DIC with thrombocytopenia and hemolysis that can worsen the already present organ system dysfunction.

HELLP syndrome is a particularly severe form of preeclampsia associated with severe maternal morbidity.

Preeclampsia has long-term implications for the health of these patients. After delivery, women with preeclampsia are at increased risk for the development of chronic hypertension, cardiovascular diseases, and psychosomatic disorders.³

Presenting Signs and Symptoms

Classic clinical findings in patients with preeclampsia include proteinuria and an associated elevation in blood pressure; when these signs develop late in the pregnancy of a previously healthy woman, the diagnosis of preeclampsia is clear. However, preeclampsia does not always occur in such a straightforward manner. For instance, a patient with chronic hypertension complicated by chronic renal disease can be difficult to differentiate from one who has preeclampsia. Likewise, seizures in pregnant patients do not always herald eclampsia, and other structural, toxic, and metabolic causes have to be considered.

Patients may have the classic symptoms of severe preeclampsia, such as seizures superimposed on hypertension and proteinuria, or may have incidentally noted hypertension and proteinuria with or without edema.

Persistent elevation in blood pressure is the hallmark of preeclampsia. Hypertension is defined as a sitting blood pressure of 140 mm Hg systolic or 90 mm Hg diastolic or greater. Blood pressure readings should ideally be taken more than 6 hours apart; however, for most patients in the emergency department (ED), if concern is high, therapy should not be delayed. Early in pregnancy, diastolic blood pressure decreases but returns to normal toward the 28th week of gestation. Therefore, a sustained diastolic blood pressure of greater than 90 mm Hg at the midpoint of pregnancy should be considered elevated unless the patient has a clearly documented history of hypertension.

If the patient’s blood pressure before pregnancy is known, an increase in systolic blood pressure of 30 mm Hg or greater and an increase in diastolic blood pressure of 15 mm Hg or greater are diagnostic of preeclampsia. In addition to hypertension, the patient will have proteinuria of 1+ or greater on urinalysis.

Patients with severe preeclampsia may have additional symptoms of organ involvement (Box 121.1),⁴ including significant edema, especially facial edema, and documented weight gain of more than 5 pounds per week. Findings ominous for severe preeclampsia include a blood pressure of 160 mm Hg systolic and 110 mm Hg diastolic or greater, visual disturbances (blurred vision or scotomata), severe headache, altered mental status, seizures (which defines eclampsia), hyperreflexia with clonus, severe epigastric or right upper quadrant pain on examination, retinal hemorrhage with exudates and papilledema (which is rare and more commonly indicates underlying chronic hypertension), bibasilar rales and evidence of frank pulmonary edema, oliguria, and petechiae and bleeding from puncture sites.

Fetal growth retardation and oligohydramnios may be seen in cases of severe preeclampsia, but this information is not usually available. Sudden onset of abdominal pain with a firm painful uterus suggests placental abruption, which complicates up to 10% of preeclamptic pregnancies.

Differential Diagnosis and Medical Decision Making

The current classification of hypertension in pregnancy is divided into four categories: preeclampsia, gestational or transient hypertension, chronic hypertension, and preeclampsia superimposed on chronic hypertension (Box 121.2).⁵ In addition, occult renal disease can be manifested as proteinuria and associated hypertension.

The differential diagnosis of severe preeclampsia is broad and distinction may be difficult, particularly with concomitant HELLP syndrome.⁶ Thrombotic thrombocytopenic purpura (TTP) and preeclampsia can have identical findings of thrombocytopenia, hemolytic anemia, renal disease, and neurologic abnormalities. In patients with preeclampsia, the hypertension, proteinuria, and edema tend to precede the hematologic findings. In patients with TTP, they generally follow and are a result of the hematologic abnormalities. However, by the time that the patient arrives in the ED, these subtle distinctions may be almost impossible to delineate.

Laboratory tests may help clarify the diagnosis and determine the severity of the preeclampsia. If proteinuria is 1+ or greater on urinalysis, a hypertensive pregnant woman should be considered to have preeclampsia unless proved otherwise. A 24-hour urine collection is more sensitive for this purpose, but its use is not realistic in the ED.

A complete blood count should be performed with a manual differential and haptoglobin assay to evaluate for hemolysis. Decreased platelet counts (<100,000/mm³) are associated with severe disease. Fibrinogen levels, fibrin split products, and a prothrombin time (PT) and partial thromboplastin time (PTT) should be ordered to evaluate for DIC, which may complicate severe preeclampsia.

A comprehensive metabolic profile should be obtained because elevated serum creatinine, especially when associated with oliguria, and elevated liver transaminases suggest severe preeclampsia. Uric acid levels should be assayed; the degree of elevation of uric acid has been shown to correlate with the severity of the preeclampsia. Elevated lactate dehydrogenase (LDH) levels indicate hemolysis but can also be a result of liver involvement. Typing plus crossmatching of blood is necessary in cases of severe preeclampsia or anticipated delivery.

HELLP syndrome is characterized by peripheral smears showing schistocytes and burr cells, elevated LDH levels (>600 U/L), elevated liver enzymes (bilirubin >1.2 and aspartate transaminase >70 U/L), and low platelet count (<100,000).⁷ In addition, the abnormal laboratory test results in patients with HELLP syndrome can be seen in the other diseases noted in Box 121.3.

Table 121.1 shows the frequency of certain signs and laboratory values that may help distinguish between several of the key conditions that mimic severe preeclampsia with HELLP syndrome.⁶

Treatment

It is important to differentiate between mild and severe preeclampsia⁸ (Table 121.2) when discussing the patient with the obstetrics consultant because acute management depends on the severity of disease, as well as fetal maturity. Recent research favors delivery over observation for gestational age older than 36 weeks.⁹

Table 121.2 Comparison of Symptoms of Severe and Mild Preeclampsia

In patients with severe preeclampsia and eclampsia, basic management involves the following measures: (1) support of maternal vital functions and initiation of laboratory test evaluation, (2) control of severe hypertension, (3) prevention and treatment of seizures, and (4) early consultation for determination of final treatment (capability of the hospital to deliver material and fetal care, decision regarding immediate delivery).¹⁰

The patient should be placed in the left lateral decubitus position with large-bore intravenous (IV) access; however, large fluid boluses should be avoided. Patients should receive supplemental oxygen and, if the airway is in danger of compromise, should be intubated, with attempts to minimize elevations in intracranial pressure. Vital signs should be monitored continuously. Fever may indicate infection, may mean that the patient has a disorder other than preeclampsia (e.g., acute fatty liver of pregnancy, TTP), or may be the result of prolonged seizures. As the maternal condition is stabilized, fetal heart rate monitoring should begin.

In preeclamptic patients, the mainstay of treatment is administration of magnesium for seizure prophylaxis when diastolic blood pressure exceeds 100 mm Hg. Magnesium is superior to phenytoin (Dilantin) or diazepam for prevention of eclamptic seizures.¹¹ The recommended dosage is 4 to 6 g of magnesium administered intravenously over a 15-minute period, followed by a maintenance infusion of 1 to 2 g/hr, with a goal of serum levels of 4 to 6 mEq/L. The maintenance dosing should be started only if the patient still has patellar reflexes and an adequate respiratory rate. Magnesium should be used cautiously in patients with renal insufficiency or oliguria.

When systolic blood pressure reaches 160 mm Hg or diastolic pressure reaches 105 mm Hg, most experts recommend the use of an antihypertensive agent. The ideal antihypertensive agent for preeclampsia is one that reduces blood pressure in a controlled manner and has minimal side effects (Table 121.3).^12,13 The exact degree of reduction is controversial, but it is reasonable to maintain diastolic blood pressure between 90 and 110 mm Hg.

Table 121.3 Priority Medications for Preeclampsia: Antihypertensive Agents

Hydralazine hydrochloride (Apresoline) has been commonly used as an antihypertensive agent for patients with severe preeclampsia. Its mechanism of action is through direct relaxation of arteriolar smooth muscle. This drug can be given as 5- to 10-mg boluses every 15 to 20 minutes until a response in blood pressure is seen. Side effects include tachycardia, nausea, vomiting, headache, and epigastric pain.

Labetalol, a combination α- and β-adrenergic blocking agent, is another commonly used medication, and some authors prefer this agent over hydralazine.¹⁴ The dose is 20 to 40 mg administered as a slow IV push every 20 to 30 minutes. This can be followed by 1 to 2 mg/min given by continuous infusion or by IV dosing every 3 hours after the blood pressure has been controlled. Side effects include flushing, orthostatic hypotension, and tremulousness. Labetalol should not be used in patients with asthma or evidence of heart failure.

Antihypertensive agents to use with caution, if at all, include nifedipine and nitroglycerin. Calcium channel blockers such as nifedipine (10 mg orally every 30 minutes) have been used for refractory cases of hypertension. However, there is concern about a precipitous decrease in blood pressure when magnesium and nifedipine are used together. Nitroglycerin, a venous (predominantly) and arterial vasodilator, has also been used for refractory cases of hypertension, particularly if the patient has evidence of congestive heart failure resulting from the hypertension. However, when high doses are used, the patient should be monitored for the development of methemoglobinemia.

Other antihypertensive agents to avoid include sodium nitroprusside and angiotensin-converting enzyme inhibitors. Sodium nitroprusside should be used only as a last resort because fetal cyanide poisoning has been reported in animal studies.¹⁵ However, if the blood pressure is not responding to other agents, use of this medication is appropriate. Angiotensin-converting enzyme inhibitors have been shown to cause fetal death in animals and possibly renal failure in neonates and thus should not be used in pregnancy. Clonidine and α-methyldopa are not administered parenterally and are therefore rarely used in initial management of preeclampsia.

The treatment of eclampsia and severe preeclampsia is delivery. The method of delivery (cesarean or vaginal) depends on gestational age, cervical maturation, and clinical status. In patients with less than 32 weeks’ gestation and mild preeclampsia, care is controversial and detailed discussion with an obstetrician is needed. If a decision is made to observe the patient, low-dose aspirin is sometimes recommended. Blood typing and crossmatching should be ordered if the severity of illness indicates the need for delivery.

Treatment of specific complications of preeclampsia includes dexamethasone, which may useful in patients with HELLP syndrome. However, this is therapy is not yet universally accepted and consultation is recommended. Betamethasone, which will accelerate fetal lung maturity after 24 hours, may also be considered. DIC should be treated with replacement of blood products and coagulation factors as indicated clinically; however, heparin is not usually recommended. Epidural anesthesia in the setting of DIC or thrombocytopenia may be contraindicated because of the risk for epidural hematoma.

Follow-Up, Next Steps in Care, and Patient Education

In pregnant women evaluated in the ED for any complaint, blood pressure should be considered carefully. Mild preeclampsia may progress rapidly to severe preeclampsia with little warning. If a pregnant patient is found to have elevated blood pressure, the initial assessment should include a complete history and physical examination with attempts to determine whether the elevated blood pressure is new or old and whether other evidence of preeclampsia is present (Fig. 121.1). If there is concern that the elevated blood pressure indicates preeclampsia, the patient will usually need admission for close monitoring and therapy.

Fig. 121.1 Algorithm for the approach to a patient with suspected preeclampsia.

BMP, Basic metabolic profile; BP, blood pressure; CBC, complete blood count; DBP, diastolic blood pressure; DIC, disseminated intravascular coagulation; LFTs, liver function tests; IV, intravenous; SBP, systolic blood pressure.

Patients with preeclampsia and eclampsia will need emergency obstetrics consultation to assist in management and admission versus transfer decisions.

Epidemiology

Vaginal bleeding occurs in about 3% to 4% of second and third trimester pregnancies. It can herald catastrophic problems for both the mother and fetus.¹⁶ Placental abruption and placenta previa are the most serious causes of vaginal bleeding in late pregnancy. In 20% of women the bleeding is due to placenta previa, and in 33% it is due to placental abruption. Placental abruption is estimated to occur in about 1% of all pregnancies. Of these pregnancies, 20% to 40% will be associated with perinatal morbidity or mortality involving the mother or fetus. Maternal death, though diminishing in incidence (0.03% of pregnant women), remains significant.¹⁷ Additionally, women who sustain trauma in pregnancy are at risk for abruption, even when the trauma appears to be minimal.

Ultrasound studies estimate that the incidence of placenta previa is higher (about 5%) in the second trimester. The incidence decreases to about 0.5% of pregnancies at delivery as the uterus enlarges and pulls the placenta away from the cervical os.

Vaginal bleeding in late pregnancy has causes other than placenta previa or placental abruption (such as cervical and vaginal abrasions or polyps) in about 50% of patients; nonetheless, these women need close follow-up. The risk for second trimester miscarriage or perinatal morbidity is as high as 30% in this group. Investigation of other causes of vaginal bleeding should be delayed until the diagnosis of placenta previa or placental abruption is ruled out. Vaginal bleeding in all patients should receive serious consideration, even if the bleeding appears to be self-limited.

Pathophysiology

Presenting Signs and Symptoms

In women with late pregnancy bleeding, there are three key historical points: painful or painless bleeding, volume of bleeding, and presence of fetal movement. The classic manifestation of placental abruption is painful vaginal bleeding associated with fetal distress. However, the clinical findings of abruption vary from asymptomatic to significant painful bleeding to catastrophic maternal or fetal death. Most women have uterine contractions and about one third have uterine hypertonus. Symptoms may also include back pain when the placental location is posterior. Fetal distress may be noted from lack of movement and fetal heart rate patterns that include fetal decelerations, reduced variability, and bradycardia. In the majority of cases the abruption is not due to trauma; however, in the ED population, trauma is an important cause. The shearing force of minor trauma such as a fall or motor vehicle crash might initiate abruption.

In contrast to placental abruption, the classic finding in patients with placenta previa is painless bleeding.¹⁶ The bleeding varies from mild to massive and from intermittent to continuous. Bleeding usually occurs after the 28th week of gestation.

Vaginal bleeding past the first trimester of pregnancy is abnormal and should be taken seriously. The patient’s obstetric history, as well as social and medical history, may contribute to the diagnosis and alert the physician to complicating factors. The onset, duration, and quantity of vaginal bleeding are relevant to determine the patient’s stability; trauma and sexual activity may stimulate bleeding. Bleeding after trauma is more likely to be due to placental abruption, whereas intercourse may provoke bleeding from placenta previa.

The duration of bleeding, estimated volume of blood lost, and number of pads used can help determine the volume of blood loss. A typical saturated pad holds about 30 mL of blood. Because several liters of blood can remain concealed in the uterus, it is easy to underestimate the volume of blood lost.

During the initial evaluation, women should be asked whether they felt any fetal movements in the past few hours. Lack of movement may indicate fetal death or compromise.

The physical examination should not include speculum or manual pelvic examination as part of the evaluation of patients with third trimester bleeding. In the presence of placenta previa, cervical manipulation may cause torrential vaginal bleeding. If the patient has had second trimester ultrasound performed with no placenta previa documented, internal examination may be performed.

The evaluation should include fundal height measurement and evidence of uterine tenderness, contractions, or a hypertonic uterus. Severe placental abruption causes uterine irritability manifested as frequent contractions with increased baseline tone (high-frequency contractions). In patients with placenta previa, the uterus should be soft, although 10% of these patients may be in labor and have contractions that should not be confused with the uterine irritability of placental abruption. Fetal descent into the pelvis should be noted, and the presenting part may be determined with Leopold maneuvers.

In cases of vaginal bleeding caused by trauma, placental abruption is highest on the list of differential diagnoses. However, if the pain is caused by trauma to other organs, the bleeding might be due to placenta previa. In about 10% of cases, abdominal pain occurs with placenta previa. The pain may be due to the bleeding or the onset of labor.

Although vaginal bleeding occurs in 80% of cases of placental abruption, some abruptions are concealed without any evidence of overt bleeding, thereby making diagnosis difficult. It is thus important to realize that abruption may be accompanied by symptoms that can be either minor or severe (shock, fetal demise, tetanic contractions).

Differential Diagnosis and Medical Decision Making

Uterine rupture is a rare but catastrophic event that should be considered in the differential diagnosis of placental abruption. It is most commonly seen in women with previous cesarean section or after severe trauma. Fetal mortality is close to 100%, and maternal mortality is significant. Bleeding may or may not be present, but there is usually severe abdominal pain and a rigid gravid abdomen. The diagnosis is made operatively or by ultrasonography. With trauma, other injuries such as liver or splenic lacerations need to be considered and ruled out.

The maternal response to volume depletion is to decrease blood flow to nonvital organs, including the uterus, with resultant fetal hypoxia manifested as bradycardia with a fetal heart rate lower than 100 beats/min. Bradycardia and fetal distress may have a variety of causes and may be present in placental abruption without maternal compromise. In addition, it should be noted that up to 20% of cases of placental abruption are initially manifested as fetal demise.

Following clinical examination, ultrasound imaging may be performed, which may result in another diagnosis in 25% to 50% of cases (Box 121.4). About 10% of pregnant patients with abdominal pain and bleeding may have preterm labor, heavy bloody show with the onset of labor, or marginal placental or subchorionic bleeding. These patients should be admitted for monitoring. Other causes of vaginal bleeding are vaginal or cervical polyps, cervical lacerations or erosions, cervical carcinoma, and vulvar injury.

Patients in the second half of pregnancy with abdominal or back pain but without vaginal bleeding should first be considered to have placental abruption because concealed hemorrhage is present in 10% of placental abruptions. Other causes of abdominal pain should also be considered, such as pyelonephritis, nephrolithiasis, appendicitis, ovarian torsion, and other abdominal processes. Abnormal laboratory findings such as blood in the urine and an elevated white blood cell count may help in the differential diagnosis.

Diagnostic Testing

In patients with third trimester bleeding, ultrasonography may be performed to rule out placenta previa, to determine fetal age and viability, and to look for placental abruption. However, only 25% to 50% of placental abruptions are identified on ultrasound, and the appearance may be unimpressive because the clot looks similar to the placenta. When abruption is seen on ultrasound, its specificity is 95%.²¹ The diagnosis of placental abruption is clinical, and the emergency physician should suspect placental abruption in a pregnant woman with significant uterine contractions and fetal distress. Monitoring of the fetal heart rate and uterine contraction (tocography) should be initiated early. The diagnosis is confirmed by examination of the placenta after delivery.

In trauma patients with abdominal pain in late pregnancy, other injuries must be considered and are best managed by a multispecialty team consisting of emergency medicine, trauma, and obstetrics. Early evaluation with focused assessment with sonography for trauma (FAST), as well as assessment of fetal size (for dates) and fetal heart rate, is key. Chest and pelvis radiographs, as well as computed tomography (CT) scans, may be necessary. Though not the test of choice for abruption, abdominal CT scans have a sensitivity of 50% to 100%, depending on the expertise of the radiologist.²² During the evaluation it is important that the fetus be monitored continuously as early as possible. Resuscitation of the mother is the best treatment for the fetus. If the mother has loss of vital signs, perimortem cesarean section should be considered. See Chapter 11, Resuscitation in Pregnancy, Chapter 79, Blunt Abdominal Trauma, and Chapter 122, Emergency Delivery and Peripartum Emergencies, for further details.

Laboratory evaluation includes a complete blood count, comprehensive metabolic profile, PT and PTT, DIC panel (fibrinogen, fibrin split products), urinalysis, and blood type and crossmatch. Anemia is a concern with both placental abruption and placenta previa. Because DIC can complicate placental abruption, it is important to perform the relevant tests. The Kleihauer-Betke test, which confirms the presence of fetal blood cells in the maternal circulation, may be performed if fetal-maternal transfusion is suspected. It is neither sensitive nor specific for abruption but quantifies that volume of fetal-to-maternal transfusion if positive.^17–19

Treatment

Basic management of vaginal bleeding in third trimester pregnancy includes determination of the hemodynamic status of the mother and resuscitation as needed, assessment of fetal condition and age by fetal monitoring and ultrasonography, and decision making about the optimal timing of delivery. Early consultation with obstetrics colleagues is critical.

The patient should be placed on her left side to increase venous return. Initial management of significant vaginal bleeding is volume resuscitation and transfusion as needed. Although normal vital signs are optimal, they may be falsely reassuring because of the physiologic increase in maternal volume. After stabilization of the mother is ensured, the status of the fetus is assessed with continuous monitoring and ultrasound imaging to determine viability and age. The fetal heart rate may be a good indicator of maternal status; however, it is not specific.

Ultrasonography will diagnose placenta previa, which is managed by delaying delivery if the patient is stable and the fetus is premature. If there is heavy bleeding or the pregnancy is near term, delivery should be undertaken by cesarean section, regardless of fetal viability.

Management of placental abruption is contingent on the viability or distress of the fetus. In cases of mild placental abruption without fetal distress and severe placental abruption with fetal mortality, infants are delivered vaginally. In cases of moderate placental abruption with fetal distress, cesarean section is preferred.

Rh-negative women should be given 300 units of RhoGAM. This dose is adequate to prevent maternal sensitization to up to 15 mL of fetal blood. A larger dose may be necessary if fetal-to-maternal transfusion is greater as determined by the Kleihauer-Betke test.

Follow-Up, Next Steps in Care, and Patient Education

Women with vaginal bleeding late in pregnancy need to be admitted. If the hospital does not have critical obstetrics and neonatal care facilities, transfer to a tertiary hospital is required.