AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria with or without edema. If hypertension and proteinuria are complicated by seizures or coma, the condition is known as eclampsia.

Pathophysiology

Eclampsia develops after the 20th week of gestation and is considered a complication of severe preeclampsia. The progression from severe preeclampsia to seizures and coma is thought to be due to hypertensive encephalopathy, vasogenic edema associated cortical ischemia, edema, or hemorrhage.

The cause of preeclampsia and later eclampsia remains unclear. Genetic, immunologic, endocrine, nutritional, and perhaps infectious agents also likely have a role in this complex process. Current research implicates uterine and placental ischemia and the subsequent release of humoral agents resulting in widespread vasoconstriction. The direct cause of the defining seizure activity of eclampsia remains unknown. Cerebral ischemia, infract, hemorrhage, and edema have all been known to occur in patients with edema, evidenced by MRI and by autopsy. Research evidence of endothelial damage in the uterus and placenta with resulting edema suggests a similar secondary central nervous system (CNS) event, but a unifying theory remains elusive.

Eclampsia is a clinical diagnosis with patients having seizures without evidence for CNS, metabolic, or other etiology of the seizure activity. Most patients have systolic BPs higher than 160 mm Hg or diastolic BPs higher than 110 mm Hg and proteinuria; however, eclampsia can occur with minimally elevated BP or elevated related to baseline and without proteinuria. Evidence of end-organ damage prior to development of seizures is common; symptoms include altered mental status; headache; visual disturbances; and abdominal pain; and signs include hemoconcentration; hemolysis, impaired liver function with elevated liver enzyme levels, and thrombocytopenia (HELLP); proteinuria; oliguria; pulmonary edema; generalized peripheral edema; microangiopathic hemolytic anemia; and fetal growth retardation.

Specific laboratory studies, invasive monitoring, and biopsy may show evidence of altered cardiovascular and pulmonary dynamics, hematologic alterations and coagulopathy, and multisystem cellular damage.

Eclampsia is most common during the antepartum period, yet 20-25% of cases occur during the postpartum period. Although postpartum eclampsia may occur as long as 3 weeks postpartum, most cases (98%) occur on the first postpartum day. Eclampsia is not the cause of seizures that occur during the first trimester or well into the postpartum period. These seizures are suggestive of CNS pathology.

The following are considered risk factors for development of preeclampsia preceding eclampsia: extremes of maternal age, primigravida, multiple gestations, molar pregnancy, preexisting hypertension, diabetes mellitus or renal disease, preexisting connective tissue or vascular disease, fetal growth restriction, genetic factors, prior history of preeclampsia or eclampsia, and family history of preeclampsia or eclampsia.

Frequency

United States

Eclampsia complicates approximately 0.05-0.2% of all pregnancies.

Mortality/Morbidity

• The most significant maternal complications of eclampsia are related to permanent CNS damage secondary to recurrent seizures or intracranial bleeding. The maternal mortality rate is 8-36%
• The definitive treatment for eclampsia is delivery of the fetus. Premature delivery and its complications often contribute to the fetal mortality rate of 13-30%. Placental infarcts, abruptio placentae, and intrauterine growth retardation also contribute to fetal demise.
• Mortality rates vary according to the level of care provided by the medical center. Patients must be treated in a facility that offers high-risk obstetric care.

Age

Eclampsia usually occurs in patients at both extremes of reproductive age; however, the risk of eclampsia is greatest in women younger than 20 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Most eclampsia patients present with hypertension and seizures, with some combination of proteinuria and edema.
• The natural progression of the disease is from symptomatic severe preeclampsia (differentiated from preeclampsia by specific vital signs, symptoms, and laboratory abnormalities) to seizures.
• Features include the following:
• • Seizure or postictal state (100%)
  • Headache (80%)
  • Generalized edema (50%)
  • Vision disturbance (40%)
  • Abdominal pain with nausea (20%)
  • Amnesia and other mental status changes

Physical

Findings at physical examination may include the following:

• Sustained systolic BP greater than 160 mm Hg or diastolic BP greater than 110 mm Hg
• Tachycardia
• Tachypnea
• Rales
• Mental status changes
• Hyperreflexia
• Clonus
• Papilledema
• Oliguria or anuria
• Localizing neurologic deficits
• Right upper quadrant (RUQ) or epigastric abdominal tenderness
• Generalized edema
• Small fundal height for the estimated gestational age
• Apprehension

Causes

• The etiology of eclampsia is not fully understood.
• Animal modes have suggested dysfunction of the uteroplacental bed related to altered endothelial and angiogenic factors and vascular implantation. This results in decreased uteroplacental perfusion pressure and ischemia and subsequent release of cytokines and reactive oxygen species. The effect is sympathetic and neurohormonal dysregulation of blood pressure, generalized vasoconstriction, and cellular and organ system dysfunction.
• Other causes may include the following:
• • Altered cardiovascular reactivity
  • Increased capillary permeability
  • Widespread vasospasm
  • Microthrombi
  • Hypertension
  • Improper implantation of the placenta
• Risk factors include the following:
• • Prior preeclampsia and eclampsia, familial incidence (Paternal and maternal inheritance, HLA, angiotensinogen gene, and altered endothelial function have all been implicated.)
  • Obesity, chronic hypertension, renal disease, thrombophilias, vascular and connective tissue disorders, gestational diabetes, and systemic lupus erythematosus
  • Multiple fetuses, hydatid mole, fetal hydrops
  • Primigravida, teenaged patient or patient older than 35 years, lower socioeconomic status

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The CBC may reveal the following:
• • Anemia due to hemolysis, hemoconcentration, or physiologic hemodilution of pregnancy
  • Thrombocytopenia ( <100,000) due to hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome
• The serum creatinine level is elevated because of decreased intravascular volume and a decreased glomerular filtration rate (GFR). Creatinine clearance (CrCl) may be less than 90 mL/min/1.73 m².
• Rule out hypoglycemia as cause of seizure or result of seizure, and rule out hyperglycemia as cause of mental status changes.
• Liver function test results may reveal the following:
• • Aspartate aminotransferase (SGOT) level higher than 72 IU/L, total bilirubin levels higher than 1.2 mg/dL, and LDH level higher than 600 IU/L
  • Elevated levels due to hepatocellular injury and HELLP syndrome
• The coagulation profile may reveal normal prothrombin (PT) and activated partial thromboplastin (aPTT) times, fibrin split products, and fibrinogen levels. Rule out associated disseminated intravascular coagulation (DIC).
• Urinalysis may reveal the following findings:
• • Proteinuria (>300 mg/24h or > 1 g/L)
  • Positive human chorionic gonadotropin (HCG) result
• Uric acid levels may be increased mildly.
• Increased T4 levels may be present.
• Evidence suggests that placental growth factors and other cellular receptors may be abnormal, allowing earlier detection of preeclampsia in patients.

Imaging Studies

• Head CT scanning
• • Obtain a CT scan of head in patients with severe preeclampsia or eclampsia and associated neurologic deficits or severe headache.
  • CT scan is used to assess intracranial hemorrhage, subarachnoid hemorrhages, or cerebrovascular accidents.
• Transabdominal ultrasonography
• • Transabdominal ultrasonography is used to estimate gestational age.
  • This may be used to rule out abruptio placentae that can complicate eclampsia.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Emergency medical services personnel should (1) secure an intravenous line with a large-bore catheter, (2) initiate cardiac monitoring and administer oxygen, and (3) transport the patient in the left lateral decubitus position.
• Supportive care includes airway support and attempted termination of any ongoing seizure with diazepam.

Emergency Department Care

• The goal of management is to limit maternal and fetal morbidity until delivery of the neonate, the only definitive treatment for eclampsia.
• Supportive care for eclampsia consists of close monitoring, invasive if clinically indicated; airway support; adequate oxygenation; anticonvulsant therapy; and BP control.
• Magnesium sulfate is the initial drug administered to terminate seizures. Compared with the traditional drugs used to terminate seizures (eg, diazepam, phenytoin [Dilantin]), magnesium sulfate has a lower risk of recurrent seizures with nonsignificant lowering of perinatal morbidity and mortality. Seizures usually terminate after the loading dose of magnesium. Once the seizures terminate, most patients note improved blood pressure control.
• Benzodiazepine or phenytoin can be used for seizures that are not responsive to magnesium sulfate.
• After the initial loading dose of magnesium, significant hypertension continues in approximately 10-15% of eclamptic patients. Hydralazine or labetalol agent can then be administered for BP control as recommended with diastolic blood pressures of 105-110 mm Hg or higher. Care must be taken not to decrease the BP too drastically; a drastic decrease can cause inadequate uteroplacental perfusion and fetal distress.
• Maintaining a diastolic BP of 90 mm Hg is the goal of antihypertensive therapy.

Consultations

Recommend immediate consultation with an obstetrician for any pregnant woman with eclampsia and further consultation to high-risk pregnancy specialists.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of therapy is to decrease BP, prevent or control convulsions, and deliver a viable neonate. The antihypertensive agent of choice is hydralazine. Alternative antihypertensives include labetalol, diazoxide, and occasionally, nitroprusside.

Drug Category: Anticonvulsants

Convulsive generalized status epilepticus in pregnancy jeopardizes both the mother and fetus. The anticonvulsant agent of choice is magnesium sulfate. However, when seizures continue after administration of magnesium, benzodiazepines are the drugs of choice.

Drug Category: Antihypertensives

A systolic BP of 160-180 mm Hg or greater or a diastolic BP of 110 mm Hg or greater should be treated with IV antihypertensives to prevent cerebral hemorrhage. Hydralazine is the DOC for BP control in eclampsia. However, parenteral hydralazine is provided to pharmacists only through special emergency request. Therefore, be prepared to use other antihypertensive agents when hydralazine is not available immediately. Labetalol has alpha-adrenergic and beta-adrenergic blocking effects and can be used for rapid control of severe hypertension.

Other antihypertensive drugs have significant adverse effects and should not be used as primary agents. Diazoxide may cause hyperglycemia and inhibit labor. Nitroprusside may cause fetal cyanide toxicity. Diuretics should be avoided because of the relative intravascular volume depletion in the patient with eclampsia.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with eclampsia require immediate obstetric consultation and admission to an intensive care setting for supportive care and treatment until delivery of the neonate.
• Patients require hospitalization, with bed rest in left lateral decubitus position.
• Airway management and adequate oxygenation should be continued.
• Anticonvulsant therapy with magnesium sulfate may be required.
• Treat continued hypertension with hydralazine or labetalol.
• Delivery of the neonate is the definitive treatment.

Transfer

• Perinatal morbidity and mortality rates vary in relation to the level of care rendered by the medical center. Patients with eclampsia require transfer to a high-risk obstetric facility that provides neonatal and maternal intensive care.
• When initially evaluating a patient with eclampsia, become familiar with the level of care that the medical center can offer the patient.

Complications

• Permanent neurologic damage from recurrent seizures or intracranial bleeding
• Renal insufficiency and acute renal failure
• Fetal changes - Abruptio placentae, oligohydramnios
• Hepatic damage and rarely hepatic rupture
• Hematologic compromise and DIC
• Death

Prognosis

• Approximately 25% of women with eclampsia have hypertension in subsequent pregnancies.
• Eclamptic multiparous women may have an increased risk for essential hypertension.
• Eclamptic multiparous women have an increased mortality rate in subsequent pregnancies, compared with primiparous women.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Preeclampsia can progress quickly to eclampsia.
• Immediately consult an obstetrician/gynecologist when the diagnosis of eclampsia is being considered.
• Seizures in the first trimester or well into the postpartum period probably are due to CNS pathology and warrant full evaluation, including CT scanning of the head, lumbar puncture (if clinical evidence of meningitis or concern for hemorrhage exists), determination of electrolyte levels, and urine or serum toxicologic screening.
• Preventing the development of preeclampsia in high-risk patients could theoretically decrease the risk of eclampsia and its complications later in pregnancy. Aspirin blocks platelet aggregation and vasospasm in preeclampsia, and it may be effective in preventing preeclampsia. Recent studies have shown that low-dose aspirin in women at high risk for preeclampsia can contribute to a decreased risk of preeclampsia, a reduction in preterm delivery rates, and a reduction in fetal death rates without increasing the risk of placental abruption. An obstetrician should directly supervise aspirin therapy in high-risk patients.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• ACOG. ACOG Practice Bulletin: Diagnosis and Management of Preeclampsia and Eclampsia: The American College of Obstetricians and Gynecologists Number 33. Jan 2002.
• Abbott J. Complications related to pregnancy. In: Emergency Medicine: Concepts and Clinical Practice. 3rd ed. 1992:1984-7.
• Brady WJ, DeBehnke DJ, Carter CT. Postpartum toxemia: hypertension, edema, proteinuria and unresponsiveness in an unknown female. J Emerg Med. Sep-Oct 1995;13(5):643-8. [Medline].
• Coomarasamy A, Honest H, Papaioannou S. Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review. Obstet Gynecol. Jun 2003;101(6):1319-32. [Medline].
• Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ. Feb 10 2001;322(7282):329-33. [Medline].
• Hals G, Crump T. The pregnant patient: guidelines for management of common life-threatening medical disorders in the emergency department. Emerg Med Rep. Mar 13 2000;21(6):57-9.
• Hansen WF. Problems in pregnancy. In: Emergency Medicine: A Comprehensive Study Guide. 4th ed. 1996: 573.
• Moussouttas M, Abubakr A, Grewal RP. Eclamptic subarachnoid haemorrhage without hypertension. J Clin Neurosci. May 2006;13(4):474-6. [Medline].
• Rivers EP. Preeclampsia, eclampsia, and other hypertensive disorders of pregnancy. In: The Clinical Practice of Emergency Medicine. 2nd ed. 1996: 315-21.
• Robinson CJ, Johnson DD, Chang EY. Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia. Am J Obstet Gynecol. Jul 2006;195(1):255-9. [Medline].
• Stennett AK, Khalil RA. Neurovascular mechanisms of hypertension in pregnancy. Curr Neurovasc Res. May 2006;3(2):131-48. [Medline].
• Which anticonvulsant for women with eclampsia?. Evidence from the Collaborative Eclampsia Trial. Lancet. Jun 10 1995;345(8963):1455-63. [Medline].

Article Last Updated: Sep 28, 2006