Eclampsia

INTRODUCTION

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Background: Eclampsia is defined as seizure activity or coma unrelated to other cerebral conditions in an obstetrical patient with preeclampsia. While the majority of the cases present in the third trimester of pregnancy or within the first 48 hours following delivery, rare cases have been reported prior to 20 weeks gestation or as late as 23 days postpartum. Eclampsia has also been described without prior development of pre-eclampsia.

Pathophysiology: Many investigators have proposed genetic, immunologic, endocrinologic, nutritional, and even infectious agents as the cause for pre-eclampsia/eclampsia. Despite extensive research, no definitive cause has been identified. Presumably, the placenta and fetal membranes play a role in the development of preeclampsia because of the prompt resolution of the disease following delivery. A common pathway thought to be associated with the development of preeclampsia is utero-placental ischemia. It is postulated that uteroplacental ischemia predisposes to the production and release of biochemical mediators that enter the maternal circulation, causing widespread endothelial dysfunction and generalized arteriolar constriction and vasospasm.

Preeclampsia/eclampsia creates a functional derangement of multiple organ systems, such as central nervous system, hematologic, hepatic, renal, and cardiovascular systems. The severity depends on medical or obstetric factors.

Systemic derangements in eclampsia include the following:

Cardiovascular

• Generalized vasospasm
• Increased peripheral vascular resistance
• Increased left ventricular stroke work index
• Decreased central venous pressure
• Decreased pulmonary wedge pressure

Hematologic

• Decreased plasma volume
• Increased blood viscosity
• Hemoconcentration
• Coagulopathy

Renal

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• Decreased glomerular filtration rate
• Decreased renal plasma flow
• Decreased uric acid clearance

Hepatic

• Periportal necrosis
• Hepatocellular damage
• Subcapsular hematoma

Central nervous system

• Cerebral Edema
• Cerebral hemorrhage

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Frequency:
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• In the US: Approximately 5% of pregnancies are complicated by preeclampsia. Of these patients, 0.5-2% will progress to eclampsia. The incidence is increased in women of low socioeconomic status, extremes of age, and primigravid state. Both preeclampsia and eclampsia account for significant maternal and fetal morbidity and mortality.

Mortality/Morbidity: Eclampsia accounts for approximately 50,000 maternal deaths worldwide annually. In the US, maternal mortality from eclampsia has been reduced with early diagnosis and aggressive management and is currently less than 1%. Fetal mortality from eclampsia has also decreased, but still remains at approximately 12%.

• Maternal complications of eclampsia may include permanent CNS damage from recurrent seizures or intracranial bleeds, renal insufficiency, and death.

• Causes of neonatal death include prematurity, placental infarcts, intrauterine growth retardation, abruptio placentae, and fetal hypoxia.

Race: Racial predilection is unclear. There may be a higher incidence of this condition in African Americans.

Sex: Only females are affected.

Age: Affects all ages, but is increased in nulliparous women less than 20 years of age. Women greater than 40 years with preeclampsia have 4 times the incidence of seizures compared to women in their 20s.

Other risk factors include the following:

• Nulliparity age greater than 35
• Preexisting hypertension or renal disease
• Poor prenatal care
• Strong family history of preeclampsia/eclampsia
• Systemic lupus erythematous
• Obstetric conditions associated with an abundance of chorionic villi: twin gestations, molar pregnancies, triploidy, and nonimmune hydrops fetalis.

CLINICAL

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History:

• Signs - Tonic-clonic seizure activity (focal or generalized)

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• Symptoms include the following:

• Headache (82.5%)

• Hyperactive reflexes (80%)

• Marked proteinuria (52%)

• Generalized edema (49%)

• Visual disturbances (44.4%)

• Right upper quadrant pain or epigastric pain (19%)

• Prior to a seizure, some patients may present with the following:

• Lack of edema (39%)

• Absence of proteinuria (21%)

• Normal reflexes (20%)

• Presentation - Approximately 70% of eclamptic seizures occur prior to delivery.

• Twenty-five percent of eclampsia cases occur before labor (antepartum).

• Fifty percent of eclampsia cases occur during labor (intrapartum).

• Twenty-five percent of eclampsia cases occur after delivery (postpartum).

• Patients with severe preeclampsia are at greater risk to develop seizures.

• Twenty-five percent of patients with eclampsia had only mild preeclampsia prior to the seizures.

Physical:

• Eclamptic seizure

• The patient may have 1 or more seizures.

• Seizures generally last 60-75 seconds.

• The patient’s face may initially become distorted, with protrusion of the eyes.

• The patient may begin foaming at the mouth.

• Respiration ceases for the duration of the seizure.

• The seizure may be divided into 2 phases:

  Phase 1 - Lasts 15-20 seconds and begins with facial twitching. The body becomes rigid, leading to generalized muscular contractions.

  Phase 2 - Lasts approximately 60 seconds. It starts in the jaw, moves to the muscles of the face and eyelids, then spreads throughout the body. The muscles begin alternating between contracting and relaxing in rapid sequence.

• A coma or a period of unconsciousness follows phase 2.

• Unconsciousness lasts for a variable period of time.

• Following the coma phase, the patient may regain some consciousness.

• The patient may become combative and very agitated.

• The patient has no recollection of the seizure.

• A period of hyperventilation occurs after the tonic-clonic seizure. This compensates for the respiratory and lactic acidosis that develops during the apneic phase.

• Seizure-induced complications may include tongue biting, head trauma, broken bones or aspiration.

Causes:

• The cause of the seizures is not clear, although several processes have been implicated in their development.

• Areas of cerebral vasospasm may be severe enough to cause focal ischemia, which may in turn lead to seizures.

• Pathologic alterations in cerebral blood flow and tissue edema induced by vasospasm may result in headaches, visual disturbances, and hypertensive encephalopathy, resulting in a seizure.

WORKUP

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Lab Studies:
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• No single lab test or set of laboratory determinations is useful in predicting maternal or neonatal outcome in women with eclampsia.

• Lab tests that should be ordered include the following:

• Complete blood count

• Platelet count

• 24-hour urine for protein/creatinine

• Electrolytes

• Liver function tests (LDH, AST)

• Uric acid

• Serum glucose

• The most common hematologic abnormality in obstetric disorders is thrombocytopenia, occurring in 17% of eclamptic patients.

• Disseminated intravascular coagulation (DIC) appears to be uncommon in eclamptic patients.

Imaging Studies:
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• A CT scan of the head, with or without contrast, may be indicated in certain patients to exclude cerebral venous thrombosis, intracranial hemorrhage, and central nervous system lesions, all of which can occur in pregnancy.

• CT is a technique that is considered safe in pregnancy when performed after the first trimester.

• Consider obtaining a CT of the head in patients (1) who have been involved in a trauma, (2) are refractory to magnesium sulfate therapy, and (3) in those with atypical presentations (such as seizures greater than 24 hours out from delivery).

• Although obtaining a CT scan in eclampsia is not routine, abnormalities can be seen in up to one-half of patients.

• Characteristic cortical hypodense areas, particularly in the occipital lobes, and diffuse cerebral edema are thought to correspond to the petechial hemorrhages and diffuse edema noted in postmortem studies.

• Reported CT scan findings - Cerebral edema

• Diffuse white matter low density areas

• Patchy area of low density

• Occipital white matter edema

• Loss of normal cortical sulci

• Reduced ventricular size

• Reported CT scan findings - Cerebral hemorrhage

• Intraventricular hemorrhage

• Parenchymal hemorrhage (high density)

• Reported CT scan findings - Cerebral infarction

• Low attenuation areas

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• Basal ganglia infarctions

• Magnetic resonance imaging (MRI) and eclampsia

• MRI is a recently developed noninvasive technique that appears to be superior to other processed for defining intracranial anatomy and pathophysiology.

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• Abnormal findings have been reported in up to 90% of women with eclampsia.

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• Findings with MRI may be increased signal at the grey-white matter junction on T2-weighted images or cortical edema and hemorrhage.

• Angiography

• The use of cerebral angiography is limited in eclampsia.

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• The principle finding seen with eclampsia on angiography is widespread arterial vasoconstriction of the intracranial vessels.

Other Tests:
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• EEG, cerebral spinal fluid studies are rarely useful in management, however they may be indicated if epilepsy or meningitis is considered in the diagnosis.

TREATMENT

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Medical Care: Eclamptic convulsions are life-threatening emergencies and require the proper treatment in order to decrease maternal morbidity and morbidity.

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• Presentation

  If the patient develops convulsions at home, she is usually brought to the hospital in a comatose (postictal) condition. These patients should be cared for by a team of qualified physicians (preferably obstetricians) and nurses. Patients should undergo continuous intensive monitoring. They should be placed in a monitored labor room with minimal noise and external stimuli.

• Initial management

  As with any seizure, the initial management is to clear the airway and give adequate oxygenation.

  The patient should be positioned in the left lateral position to help improve uterine blood flow and obstruction of the vena cava by the gravid uterus. The patient should be protected against maternal injury during the seizure.

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  • The guardrails should be up on the bed.

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  • A padded tongue blade placed between the teeth

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  • Suction secretions from the patient's mouth.

• Intravenous access

  After the seizure has ended, a 16- to 18-gauge intravenous line should be obtained for drawing labs and administering fluids. Intravenous fluids should be limited to isotonic solutions to replace urine output and about 700 mL/day to replace insensible losses.

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• Control of the seizure

  Do not attempt to shorten or abolish the initial seizure. A syringe containing 2-4 g of magnesium sulfate should be the only anticonvulsant at the bedside. Magnesium sulfate is given intramuscularly or intravenously to decrease and prevent further convulsions.

• Laboratory workup

  A complete blood count, chemistry panel, and liver function tests should be drawn. A urinalysis should be sent to evaluate for proteinuria and a 24-hour urine collection for protein initiated.

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• Hypertension control

  Blood pressure should be recorded every 10 minutes. Blood pressures should be controlled (diastolics 90-100 mm Hg) with the administration of antihypertensive medications (hydralazine or labetalol).

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• Monitoring

  All patients should be carefully monitored as to neurologic status, urine output, respirations, and fetal status. An indwelling Foley catheter should be placed in the bladder to help collect and record urine output.

• Invasive monitoring

  Pulmonary artery pressure monitoring may be necessary for accurate fluid management in eclamptic patients. This is particularly important in patients that have evidence of pulmonary edema or oliguria/anuria.

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• Assessment of medical condition

  Once the seizure is controlled and the patient has regained consciousness, the general medical condition is assessed. Induction of labor may be initiated when the patient is stable.

• Delivery

  Delivery is the treatment for eclampsia after proper stabilization. If the patient is undelivered, no attempt should be made to deliver the infant either vaginally or by cesarean section until the acute phase of the seizure or coma has passed. The mode of delivery should be based on obstetric indications, but should be chosen with an awareness of the fact that vaginal delivery is preferable from a maternal standpoint.

  In the absence of fetal malpresentation or fetal distress, oxytocin should be initiated to induce labor in the following situations:

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  • Thirty weeks gestation or greater, irrespective of the cervical dilation or effacement

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  • Prior to 30 weeks gestation with a favorable cervix

  An unfavorable cervix with a gestational age of 30 weeks or less, once stabilized, should be delivered electively by cesarean section. This approach is preferred because pregnancies prior to 30 weeks gestation with eclampsia have a higher risk of complications intrapartum.

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  • Fetal growth retardation (30%)

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  • Fetal distress (30%)

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  • Abruption (23%)

• Fetal Monitoring

  Fetal heart rate and intensity of the contractions should be closely monitored. Fetal bradycardia is a common finding following the eclamptic seizure and has been reported to last from 30 seconds to 9 minutes.

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  • The interval from the onset of the seizure to the fall in the fetal heart rate is typically 5 minutes.

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  • There may be a transitory fetal tachycardia following the bradycardia.

  During the recovery phase, the fetal heart rate tracing may reveal a loss of beat-to-beat variability and late decelerations. The mechanism for the fetal tracing abnormalities is most likely due to a decrease in uterine blood flow caused by the intense vasospasm and uterine hyperactivity during the convulsion.

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  • If the fetal heart tracing does not improve following a seizure, other conditions should be considered.

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  • Growth restricted and preterm fetuses may take longer to recover following a seizure.

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  • Consider placental abruption if uterine hyperactivity remains and fetal bradycardia persists.

Surgical Care:

• Patients with eclampsia may need to be delivered immediately by cesarean section, depending on the maternal and fetal condition.

• It is important to stabilize the patient first before moving towards cesarean delivery during the acute phase because delivery may aggravate oliguria and other manifestations of the disease.

• The anesthesiologist should be informed of the maternal condition and may be helpful if endotracheal intubation or an operative delivery is necessary.

• For non-emergent cesarean delivery, epidural anesthesia is preferred and can be induced in a steplike fashion, being careful not to cause maternal hypotension.

• The use of spinal anesthesia is controversial because of the possibility of extreme sympathetectomy, resulting in maternal hypotension and uteroplacental insufficiency.

Consultations:

• An experienced obstetrician should be consulted immediately.
  Consideration for Maternal-Fetal medicine consultation should be given, with transport to a tertiary care site after stabilization if it is in the fetal or maternal best interest.

• In the event of prematurity or fetal compromise, a pediatrician or neonatologist should be consulted.

Diet:

• Eclamptic patients should have nothing by mouth until medically stabilized.

• During a seizure, it is important to help maintain the patient’s airway, being careful to help avoid aspiration of stomach contents.

Activity:

• Strict bedrest

• Left lateral hip roll to help improve uterine blood flow to the fetus

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity, prevent complications, and correct eclampsia. DOC include magnesium sulfate, phenytoin, diazepam, hydralazine, labetalol, nifedipine.
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Drug Category: Anticonvulsants -- Prevent seizure recurrence and terminate clinical and electrical seizure activity.

Drug Category: Antihypertensives -- Hypertension associated with eclampsia is often controlled adequately by stopping the seizure.
Antihypertensive medications are used for diastolic blood pressures >110 mm Hg. Goal of therapy is to keep diastolic blood pressure in the range of 90-100 mm Hg.
Antihypertensive therapy has 2 main goals: (1) reducing maternal morbidity and mortality associated with seizures, cerebral vascular accidents and pulmonary embolism and (2) reducing fetal morbidity and mortality secondary to intrauterine growth restriction, placental abruption and infarcts.
Uterine hypoperfusion may result if blood pressure is lowered too quickly. Uterine vasculature is always maximally vasodilated and a decrease in maternal blood pressure tends to decrease uteroplacental perfusion.
Although total body water in eclamptic patients is excessive, intravascular volume is contracted and eclamptic women are very sensitive to further volume changes. Hypovolemia will result in decreased uterine
perfusion. Therefore, diuretics and hyperosmotic agents should be avoided in eclampsia without prior assessment of intravascular volume.
Drugs used most commonly for hypertension in pregnancy are hydralazine and labetalol. Nifedipine has been used as well to control hypertension, but is less accepted.

FOLLOW-UP

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Further Inpatient Care:
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• Blood pressure, neurologic status, and urine output should be monitored closely.

Further Outpatient Care:
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• Eclamptic patients should be followed up postpartum to evaluate for evidence of essential hypertension, residual deficits from the eclamptic seizure, and patient education.

In/Out Patient Meds:
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• This disease is treated as an inpatient, as described above. Outpatient care plays no role in management.

Transfer:
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• It is clear that eclampsia poses a risk of considerable maternal and neonatal morbidity and mortality. All eclamptic patients should be managed at a tertiary care center.

Deterrence/Prevention:
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• Routine prenatal care

• Early diagnosis and aggressive management

Complications:
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• Up to 56% of eclamptic patients may have transient deficits, including cortical blindness.

• Most women do not develop long-term sequelae from eclamptic seizures, but should be followed closely for resolution of symptoms.

• Maternal as well as fetal death can be a consequence of eclampsia and its complications.

Prognosis:
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• Approximately 25% percent of eclamptic women will have hypertension in subsequent pregnancies.

• Only 5% of patients with hypertension will develop severe preeclampsia.

• Approximately 2% will develop eclampsia with future pregnancies.

• Multiparous women with eclampsia may be at higher risk for development of essential hypertension.

• Multiparous women with eclampsia have a higher mortality in subsequent pregnancies than primiparous women.

Patient Education:
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• The patient should be advised and educated on the course of their disease and any residual problems.

• The patient should be educated on prevention and avoidance with regard to future pregnancies by obtaining adequate prenatal care.

• If the patient has preexisting hypertension, she should have good control prior to conception and throughout pregnancy. She should be followed closely for recognition and treatment of early preeclampsia.

MISCELLANEOUS

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Medical/Legal Pitfalls:
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• The mode of delivery should be based on obstetric indications, with the understanding that vaginal delivery is preferable from a maternal standpoint.

• When emergent cesarean delivery is indicated, it is important to substantiate the absence of disseminated intravascular coagulopathy (DIC) prior to the procedure.

• Fetal bradycardia is extremely common following an eclamptic seizure and usually resolves within 10 minutes. Consider placental abruption if uterine hyperactivity remains and fetal bradycardia persists.

• Cervical examination should not be overlooked. The delivery mode may be largely dependent on the cervical status.

• Fluid management is critical in the eclamptic patient.

• Avoid the use of multiple agents to abate eclamptic seizures.

• It is important to rule out eclampsia in an obstetrical patient who has been involved in an unexplained trauma.

Special Concerns:

• It is important not to overlook other neurologic causes, particularly if the seizure occurs more than 24 hours after delivery.

• When preeclampsia occurs in the early second trimester (14-20 week of gestation), the diagnosis of hydatiform mole or choriocarcinoma should be considered.

• Eclampsia should always be considered in a visibly pregnant patient with a seizure episode. A pregnant patient who has been involved in an unexplained trauma (such as a single-vehicle auto accident) without obvious cause should be evaluated for eclampsia.