WORKUP	Section 5 of 10
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Lab Studies:

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

• Laboratory studies that should be ordered include the following:

• Complete blood cell count

• Platelet count

• Twenty-four–hour urine for protein/creatinine

• Electrolytes

• Liver function tests (ie, lactate dehydrogenase [LDH], aspartate aminotransferase [AST])

• Uric acid

• Serum glucose

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

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

Imaging Studies:

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

• Consider obtaining a CT scan of the head in patients (1) who have been involved in a trauma, (2) who are refractory to magnesium sulfate therapy, and (3) who have atypical presentations (such as seizures >24 h after delivery).

• Although obtaining a CT scan in eclampsia is not routine, abnormalities can be observed in as many as 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

  • Basal ganglia infarctions

• Magnetic resonance imaging and eclampsia

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

• Abnormal findings have been reported in as many as 90% of women with eclampsia.

• 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.

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

Other Tests:

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

	TREATMENT	Section 6 of 10
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Medical Care: Eclamptic convulsions are life-threatening emergencies and require the proper treatment to decrease maternal morbidity and mortality.

• Presentation: If the patient develops convulsions at home, she usually is brought to the hospital in a comatose (ie, 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 administer 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, ie, the guardrails should be up on the bed, a padded tongue blade is placed between the teeth, and secretions are suctioned from the patient's mouth.

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

• 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 administered intramuscularly or intravenously to decrease and prevent further convulsions.

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

• Hypertension control: Record blood pressure every 10 minutes. Control blood pressure (diastolic 90-100 mm Hg) with administration of antihypertensive medications (ie, hydralazine, labetalol).

• Monitoring: Carefully monitor the neurologic status, urine output, respirations, and fetal status for all patients. 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 who have evidence of pulmonary edema or oliguria/anuria.

• 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 delivery 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:
  • At 30 weeks' gestation or greater, irrespective of the cervical dilation or effacement

  • Prior to 30 weeks' gestation with a favorable cervix

• Patients with an unfavorable cervix with a gestational age of 30 weeks or less, once stabilized, should be delivered electively by cesarean delivery. This approach is preferred because pregnancies prior to 30 weeks' gestation with eclampsia have a higher risk of complications intrapartum. Intrapartum complications include the following:
  • Fetal growth retardation (30%)

  • Fetal distress (30%)

  • Abruption (23%)

• Fetal monitoring

• Fetal heart rate and intensity of the contractions should be monitored closely. Fetal bradycardia is a common finding following the eclamptic seizure and has been reported to last from 30 seconds to 9 minutes. The interval from the onset of the seizure to the fall in the fetal heart rate is typically 5 minutes. Transitory fetal tachycardia may occur 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. If the fetal heart tracing does not improve following a seizure, other conditions should be considered. Growth restricted and preterm fetuses may take longer to recover following a seizure. Consider placental abruption if uterine hyperactivity remains and fetal bradycardia persists.

Surgical Care:

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

• Stabilize the patient before initiating 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 nonemergent 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.

• Consider consultation with a maternal-fetal medicine specialist, 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:

• Patients with eclampsia should have nothing by mouth until medically stabilized.

• During a seizure, maintaining the patient's airway and being careful to help avoid aspiration of stomach contents is important.

Activity:

• Strict bedrest

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

	MEDICATION	Section 7 of 10
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The goals of pharmacotherapy are to reduce morbidity, prevent complications, and correct eclampsia. Drugs of choice include magnesium sulfate, phenytoin, diazepam, hydralazine, labetalol, and nifedipine.

Drug Category: Anticonvulsants -- Prevent seizure recurrence and terminate clinical and electrical seizure activity.

Drug Name	Magnesium sulfate -- Several studies have revealed that magnesium sulfate is the drug of choice for treating eclamptic seizures. Magnesium sulfate is successful in controlling seizures in >95% of cases. Agent has physiologic advantages to the fetus by increasing uterine blood flow. Mechanism of action of magnesium sulfate therapy is that it inhibits the release of acetylcholine at the motor endplate. In addition, magnesium has a direct effect on skeletal muscle by virtue of its competitive antagonistic effects with calcium. Magnesium sulfate is excreted exclusively by the kidneys and has little antihypertensive effect. It is an effective anticonvulsant and helps prevent recurrent seizures and maintain uterine and fetal blood flow. Can be administered both IV and IM. Intravenous route is preferred over IM route because administration is controlled more easily and time to therapeutic levels is shorter. Intramuscular administration of magnesium sulfate tends to be more painful and less convenient. If IV access or close patient monitoring is unavailable, this is an effective therapy. The goals of magnesium therapy are to terminate ongoing seizures and prevent further seizures. Patient should be evaluated qh to assure that deep tendon reflexes are present, respirations are at least 12 breaths per min, and urine output is at least 100 mL during the preceding 4 h. When using magnesium sulfate IV, close monitoring of patient and fetus is necessary. Magnesium therapy usually is continued for 12-24 h following delivery and may be stopped when the hypertension resolves and the patient has shown adequate diuresis. Renally compromised patients should be monitored with magnesium levels, with aggressive adjustments made to facilitate levels at 6-8 mg/dL. Patients with increased urine output may need maintenance dose increased to 3 g/h to maintain therapeutic levels. Monitor patient for signs of worsening condition and magnesium toxicity. The Parkland IM protocol is as follows: Magnesium sulfate 4 g IV over 5 min, plus magnesium sulfate 10 g deep IM (3-in needle) divided in both buttocks and mixed with 1 mL 2% lidocaine. If a seizure persists more than 15 min after above dose, administer an additional 2 g of magnesium sulfate IV over 3-5 min. Magnesium sulfate 5 g IM q4h, starting 4 h later unless patellar reflexes are absent, respiratory depression occurs, or urine output is <100 mL in the prior 4 h. Therapeutic levels are 4.8-8.4 mg/dL. With the above protocol, serum magnesium levels usually are 4-7 mg/dL in a patient with an average volume of distribution and normal renal function. Actual serum magnesium levels are monitored only in patients with symptomatic magnesium toxicity or renal compromise. Patients may have seizures while receiving magnesium sulfate. If seizure occurs in first 20 min after loading dose, the convulsion usually is short, and no additional treatment is indicated. If seizure occurs >20 min after the loading dose, an additional 2-4 g of magnesium may be administered.
Adult Dose	Initial: 4-6 g bolus IV over 15-20 min; if convulsion occurs after initial bolus, an additional 2 g IV over 3-5 min may be administered Approximately 10-15% of patients will have another convulsion after the loading dose Maintenance: 2-4 g/h IV maintenance drip If magnesium level is >10 mg/dL at 4 h after initial bolus, decrease the maintenance dose
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis; or myasthenia gravis
Interactions	Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Pregnancy	A - Safe in pregnancy
Precautions	Always monitor for loss of reflexes, respiratory depression, and decreased urine output; magnesium infusion should be stopped for evidence of hypermagnesemia, and patient may require assisted ventilation; maternal dose-related adverse effects at various serum levels include CNS depression at 6-8 mg/dL, loss of deep tendon reflexes at 8-10 mg/dL, respiratory depression at 12-17 mg/dL, coma at 13-17 mg/dL, and cardiac arrest 19-20 mg/dL; calcium gluconate 1 g IV may be administered slowly for evidence of magnesium toxicity

Drug Name	Phenytoin (Dilantin) -- Phenytoin has been used successfully in eclamptic seizures, but cardiac monitoring is required secondary to associated bradycardia and hypotension. The central anticonvulsant effect of phenytoin is by stabilizing neuronal activity by decreasing the ion flux across depolarizing membranes. Some benefits to using phenytoin are that it can be continued orally for several days until the risk of eclamptic seizures has subsided, it has established therapeutic levels that are easily tested, and no known neonatal adverse effects are associated with short-term usage.
Adult Dose	10 mg/kg loading dose IV infused no faster than 50 mg/min, followed by maintenance dose started 2 h later at 5 mg/kg
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Interactions	Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase phenytoin toxicity; phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; phenytoin may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid
Pregnancy	D - Unsafe in pregnancy
Precautions	Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several mo thereafter to monitor for blood dyscrasias; discontinue use if a skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugars); discontinue use if hepatic dysfunction occurs

Drug Name	Diazepam (Valium) -- Has also been used in emergencies to control eclamptic seizures but has a short CNS half-life and significant fetal CNS depressant effects. Diazepam should not be administered to stop or shorten the initial seizure, especially if IV access or the ability to rapidly intubate the patient is not readily available.
Adult Dose	Up to 5 mg IV over a 60-s period
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; narrow-angle glaucoma
Interactions	Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause phlebitis and venous thrombosis and should not be administered if IV line is not secured; may cause maternal apnea and cardiac arrest if infused too quickly; neonatal adverse effects include respiratory depression, hypotonia, and poor feeding; sodium benzoate preservative competes with bilirubin for albumin binding, thus predisposing the infant to kernicterus

Drug Category: Antihypertensives -- Hypertension associated with eclampsia often is controlled adequately by stopping the seizure.

Antihypertensive medications are used for diastolic blood pressures >110 mm Hg. The goal of therapy is to maintain 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, strokes, 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 always is maximally vasodilated, and a decrease in maternal blood pressure tends to decrease uteroplacental perfusion.

Although total body water in patients with eclampsia is excessive, intravascular volume is contracted and women with eclampsia are very sensitive to further volume changes. Hypovolemia results in decreased uterine perfusion. Therefore, diuretics and hyperosmotic agents should be avoided in eclampsia without prior assessment of intravascular volume.

	MISCELLANEOUS	Section 9 of 10
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Medical/Legal Pitfalls:

• 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, substantiating the absence of DIC prior to the procedure is important.

• 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 patients with eclampsia.

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

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

Special Concerns:

• Do not overlook other neurologic causes, particularly if the seizure occurs more than 24 hours after delivery.

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

• Eclampsia always should 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 for seizure should be evaluated for eclampsia.