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Eclampsia Author Errol R Norwitz, MD, PhD

Section Editor Charles J Lockwood, MD

Deputy Editor Vanessa A Barss, MD

Last literature review for version 17.1: enero 1, 2009 | This topic last updated: noviembre 13, 2008 INTRODUCTION — Eclampsia refers to the occurrence of one or more generalized convulsions and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions [1]. The clinical manifestations can appear anytime from the second trimester to the puerperium. In the past, eclampsia was thought to be the end result of preeclampsia (hence the nomenclature); however, it is now clear that seizures should be considered merely one of several clinical manifestations of severe preeclampsia (show table 1), rather than a separate disease. Despite advances in detection and management, preeclampsia/eclampsia remains a common cause of maternal death [2]. The diagnosis and management of eclampsia will be reviewed here. Issues related to preeclampsia are discussed separately. (See "Pathogenesis of preeclampsia", see "Clinical features, diagnosis, and long-term prognosis of preeclampsia", see "Management of preeclampsia", and see "Prevention of preeclampsia"). INCIDENCE AND EPIDEMIOLOGY — An eclamptic seizure occurs in approximately 0.5 percent of mildly preeclamptic women and 2 to 3 percent of severely preeclamptic women [3]. The incidence of eclampsia has been relatively stable at 4 to 6 cases per 10,000 live births in developed countries [4,5,53]. In developing countries, however, the incidence varies widely: from 6 to 100 cases per 10,000 live births [6]. Risk factors for eclampsia are similar to those for preeclampsia (show table 1A). Nonwhite, nulliparous women from lower socioeconomic backgrounds are the group at highest risk of developing eclampsia. Peak incidence is in the teenage years and low twenties, but there is also an increased incidence in women over 35 years of age. Timing in pregnancy — Eclampsia prior to 20 weeks of gestation is rare and should raise the possibility of an underlying molar pregnancy or antiphospholipid syndrome. (See "Gestational trophoblastic disease: Epidemiology, clinical manifestations and diagnosis" and see "Obstetrical manifestations of the antiphospholipid syndrome"). Approximately one-half of all cases of eclampsia occur prior to term, with more than one-fifth occurring before 31 weeks of gestation [4]. Just over one-third of cases occur at term, developing intrapartum or within 48 hours of delivery. Late postpartum eclampsia (ie, eclamptic seizures developing greater than 48 hours, but less than four weeks postpartum) accounts for the remainder (13 to 16 percent) and represents as many as one-quarter of all postpartum cases [7-9]. Looked at in another way, the timing and frequency of eclampsia is antepartum (38 to 55 percent), intrapartum (13 to 36 percent), less than or equal to 48 hours postpartum (5 to 39 percent), and greater than 48 hours postpartum (5 to 17 percent) [5,10]. PATHOGENESIS OF SEIZURES — The exact cause of seizures in women with eclampsia is not known. The following two hypotheses have been proposed [11]: Cerebral overregulation in response to high systemic blood pressure results in vasospasm of cerebral arteries, underperfusion of the brain, localized ischemia/infarction, and


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cytotoxic (intracellular) edema. Loss of autoregulation of cerebral blood flow in response to high systemic pressure (ie, hypertensive encephalopathy) results in hyperperfusion, endothelial damage, and vasogenic (extracellular) edema. (See "Reversible posterior leukoencephalopathy syndrome", section on Eclampsia). A classic report of autopsies performed shortly after death of eclamptic women described the neurological findings in eclamptic women [12]. The brains of more than 50 percent of the women who died within two days of seizures displayed cerebral hemorrhages. Petechial cortical hemorrhages were most common, especially involving the occipital lobe. Diffuse cerebral edema and gross hemorrhage were noted less frequently. Cerebral venous thrombosis was common in woman with postpartum eclampsia. Additional findings were observed in the largest magnetic resonance imaging study of eclampsia, which involved 27 nulliparous eclamptic women without neurologic deficit [13]. Twenty-five of these women had evidence of cerebral edema, typically involving the subcortical white and adjacent gray matter in the parieto-occipital lobes. Six women had restricted diffusion suggestive of infarction and five of the six had persistent imaging abnormalities six to eight weeks later, but their neurologic examinations remained normal. The authors hypothesized that hypertensive encephalopathy with hyperperfusion, vasogenic edema, and endothelial damage caused the eclamptic seizures and that progressive edema, rather than vasospasm, led to focal areas of cerebral hypoperfusion and, ultimately, infarction in the most severe cases. The pathogenesis of preeclampsia is reviewed elsewhere. (See "Pathogenesis of preeclampsia"). CLINICAL MANIFESTATIONS AND DIAGNOSIS Maternal — Eclampsia is a clinical diagnosis based upon evidence of one or more generalized convulsions and/or coma in a preeclamptic woman and in the absence of other neurologic conditions. Eclamptic seizures are almost always self-limiting and seldom last longer than three to four minutes (usual duration 60 to 75 seconds). Characteristics of generalized, tonic-clonic seizures are listed in the table (show table 2). Symptoms that may occur before the seizure include persistent frontal or occipital headache, blurred vision, photophobia, right upper quadrant or epigastric pain, and altered mental status. The diagnosis of preeclampsia may not be suspected prior to the development of seizures in women with relative hypertension (ie, blood pressure elevated compared with patient's baseline, but less than 140/90 mmHg) and no proteinuria [4,14,15]. (See "Can eclampsia be predicted?" below). In general, women with typical eclamptic seizures who do not have focal neurologic deficits or prolonged coma do not require diagnostic evaluation with either electroencephalographic or cerebral imaging studies [16]. If cerebral imaging is performed, magnetic resonance imaging is the optimal study. Fetal — Fetal bradycardia lasting at least three to five minutes is a common finding during and immediately after an eclamptic seizure, and does not necessitate emergent cesarean delivery. Stabilizing the mother by administering anticonvulsant drugs and oxygen and treating severe hypertension (if present) can help the fetus recover in-utero from the effects of maternal hypoxia, hypercarbia, and uterine hyperstimulation. Resolution of maternal seizure activity is associated with compensatory fetal tachycardia and loss of variability, sometimes associated with transient fetal heart rate decelerations [17]. If the fetal heart rate tracing remains nonreassuring for more than 10 to 15 minutes with no improvement despite maternal and fetal resuscitative interventions, then the possibility of occult abruption and emergent delivery should be considered [10]. DIFFERENTIAL DIAGNOSIS — Eclamptic seizures are clinically and electroencephalographically

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indistinguishable from other generalized tonic-clonic seizures. (See "Clinical neurophysiology", section on the Electroencephalogram). Clinical conditions other than eclampsia that should be considered when evaluating a pregnant woman who has had a seizure include: Stroke (hemorrhage, arterial or venous thrombosis). (See "Overview of the evaluation of stroke"). Hypertensive disease (hypertensive encephalopathy, pheochromocytoma). (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis"). Space-occupying lesions of the central nervous system (brain tumor, abscess). (See "Clinical presentation and diagnosis of brain tumors"). Metabolic disorders (hypoglycemia, uremia, inappropriate antidiuretic hormone secretion resulting in water intoxication). (See "Manifestations of hyponatremia and hypernatremia" and see "Overview of hypoglycemic disorders"). Infection (meningitis, encephalitis). (See "Viral encephalitis in adults" and see "Clinical features and diagnosis of acute bacterial meningitis in adults"). Thrombotic thrombocytopenic purpura or thrombophilia. (See "Diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults" and see "Inherited thrombophilias in pregnancy"). Idiopathic epilepsy. (See "Risks associated with epilepsy and pregnancy"). Use of illicit drugs (eg, methamphetamine, cocaine). Cerebral vasculitis. (See "Primary angiitis of the central nervous system"). Reversible posterior leukoencephalopathy syndrome (RPLS) [18]. RPLS is a common clinical syndrome resulting from a number of different causes that are grouped together because of similar findings on neuroimaging. One such cause is hypertensive encephalopathy in the setting of preeclampsia/eclampsia. The pathogenesis is unclear, but appears to be related to disordered cerebral autoregulation and endothelial dysfunction. (See "Reversible posterior leukoencephalopathy syndrome"). These etiologies are particularly important in pregnant women who seize in the first half of pregnancy when eclampsia is rare and in those with focal neurologic deficits, prolonged coma, or atypical eclampsia. The approach to evaluation and treatment of noneclamptic seizures is discussed separately. (See "Evaluation of the first seizure in adults"). MANAGEMENT — A number of management strategies have been developed to prevent maternal and fetal complications resulting from eclampsia during the peripartum period. General principles — If the seizure is witnessed, maintenance of airway patency and prevention of aspiration should be the first responsibilities of management. The gravida should be rolled onto her left side. A bed with raised, padded side rails provides protection from trauma. Supplemental oxygen (8 to 10 L/min) via a face mask has been recommended to treat hypoxemia due to hypoventilation during the convulsive episode [10]. The immediate issues in caring for an eclamptic woman include: Prevention of maternal hypoxia and trauma Management of severe hypertension, if present Prevention of recurrent seizures Evaluation for prompt delivery.


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The definitive treatment of eclampsia is delivery, irrespective of gestational age, to reduce the risk of maternal morbidity and mortality from complications of the disease. Treatment of hypertension — Strokes account for 15 to 20 percent of deaths from eclampsia. The general risk of stroke in the nonpregnant population correlates directly with the degree of elevation in systolic and diastolic pressures (show figure 1) [19]. It is not clear whether there is a threshold pressure above which emergent therapy should be instituted in pregnant hypertensive women [20]. Most experts recommend aggressive antihypertensive therapy for sustained diastolic pressures greater than 105 to 110 mmHg or systolic blood pressures greater than or equal to 160 mmHg [21], although the validity of thresholds has not been tested prospectively. The cerebral vasculature of women with underlying chronic hypertension can probably tolerate higher systolic pressures without injury, while adolescents with normally low blood pressures may benefit from starting treatment at lower blood pressure levels. (See "Management of hypertension in pregnancy"). Options for treatment include hydralazine (beginning with 5 mg intravenously, followed by 5 to 10 mg boluses as necessary every 20 minutes) or labetalol (beginning with 10 or 20 mg intravenously followed by doubling the dose at 10-minute intervals up to 80 mg for a maximum total cumulative dose of 220 to 230 mg [eg, 20-40-80-80 mg or 10-20-40-80-80 mg]). Although clinical trials have not adequately addressed the question of how aggressively to lower a preeclamptic patient's blood pressure, many experts consider a reasonable goal to be a systolic pressure of 140 to 155 mmHg and diastolic pressure of 90 to 105 mmHg. Data supporting this recommendation are provided separately. (See "Management of hypertension in pregnancy"). Women who do not improve rapidly following control of seizures and hypertension, or those who develop localizing neurologic signs, should be evaluated further. (See "Evaluation of the first seizure in adults"). The use of antihypertensive agents to control mildly elevated blood pressure in the setting of preeclampsia/eclampsia has not been shown to alter the course of the disease, nor to diminish perinatal morbidity or mortality [22-24]. Pharmacologic treatment of mild hypertension is not recommended, as neither maternal nor fetal benefits have been demonstrated. Treatment of convulsions — The initial convulsion is usually of short duration and often occurs in a setting where intravenous access and drugs are not readily available. Therefore, treatment is primarily directed at prevention of recurrent convulsions rather than control of the initial seizure. The drug of choice is magnesium sulfate. Prevention of recurrent convulsions — Approximately 10 percent of eclamptic women will have repeated seizures if managed expectantly [25]. There is universal agreement that women with eclampsia require anticonvulsant therapy to prevent further seizures and the possible complications of repeated seizure activity: neuronal death, rhabdomyolysis, metabolic acidosis, aspiration pneumonitis, neurogenic pulmonary edema, and respiratory failure. However, the choice of agent has been controversial. Obstetricians favor magnesium sulfate as the drug of choice for prevention of recurrent eclamptic seizures, whereas neurologists tend to favor anticonvulsants traditionally used in nonpregnant individuals, such as phenytoin or diazepam. The following evidence appears to have resolved this dispute in favor of magnesium sulfate: (1) The Eclampsia Trial Collaborative Group conducted two prospective trials in which 905 eclamptic women were randomly assigned to receive either magnesium or diazepam and another 775 eclamptic women were randomly assigned to receive either magnesium or phenytoin [26]. The primary outcome measures were the rates of recurrent seizures and maternal death. Magnesium sulfate was significantly more effective than either diazepam or phenytoin: Women allocated to magnesium sulfate therapy had one-half the rate of recurrent convulsions of those allocated to diazepam (13 and 28 percent, respectively). There were no other significant differences in maternal or perinatal mortality and/or morbidity


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between the two groups. Women allocated to magnesium sulfate had one-third the rate of recurrent convulsions of those allocated to phenytoin (6 versus 17 percent). In this arm of the study, women who received magnesium were less likely to be admitted to an intensive care facility (17 versus 25 percent), less likely to require ventilatory support (15 versus 23 percent), and less likely to develop pneumonia (4 versus 9 percent) compared with women who were given phenytoin. There were no other significant differences in maternal mortality or perinatal outcome between the two groups. (2) A series of systematic reviews reported magnesium sulfate was safer and more effective than phenytoin, diazepam, or lytic cocktail (ie, chlorpromazine, promethazine and pethidine) for prevention of repeat seizures in eclamptic women [27-29]. In summary, randomized controlled trials of magnesium sulfate for prevention of recurrent seizures in women with eclampsia have demonstrated this drug can reduce the rate of recurrent seizures by one-half to two-thirds (RR 0.44, 95% CI 0.32-0.51) and can reduce the rate of maternal death by one-third (RR 0.62, 95% CI 0.39-0.99) [3]. Additional advantages of magnesium sulfate therapy include lower cost, ease of administration (eg, cardiac monitoring is not required), and less sedation than either diazepam or phenytoin. Magnesium also appears to selectively increase cerebral blood flow and oxygen consumption in women with preeclampsia [30]; this is not true for phenytoin [31]. Administration of magnesium sulfate — The initial dose of magnesium sulfate recommended by experts varies from 4 to 6 g intravenously over 15 minutes [32]. We use 6 g. This dose will achieve resolution of an ongoing convulsion and provide the loading dose prior to maintenance therapy for prevention of recurrences. An alternative dose/route is magnesium sulfate 5 g intramuscularly into each buttock; however, the onset of a therapeutic effect will be slower and intramuscular injection is painful. These doses may be given safely even in the presence of renal insufficiency. Magnesium sulfate is contraindicated in women with myasthenia gravis since it can precipitate a severe myasthenic crisis. Concurrent use of magnesium sulfate with calcium channel blockers may result in hypotension. The maintenance dose of magnesium sulfate after the initial 6 g loading dose is 2 to 3 g/hour administered as a continuous intravenous infusion; alternatively, 5 g can be given intramuscularly every four hours, but this is painful. The maintenance phase is given only if a patellar reflex is present (loss of deep tendon reflexes is the first manifestation of symptomatic hypermagnesemia), respirations are greater than 12 per minute, and urine output is over 100 mL in four hours. Following serum magnesium levels is not required if the woman's clinical status is closely monitored for evidence of potential magnesium toxicity. There does not appear to be a clear threshold magnesium concentration for insuring the prevention of convulsions, although a range of 4.8 to 8.4 mg/dL has been recommended [33]. The dose should be adjusted according to the clinical response of individual patients. Calcium gluconate (1 g intravenously) may be administered to counteract magnesium toxicity, if necessary. Management of persistent convulsions — Recurrent convulsions occurring in patients on maintenance magnesium sulfate therapy can be treated with an additional bolus of 2 grams of magnesium sulfate over 15 to 20 minutes, with careful monitoring for signs of magnesium toxicity (see above). If two such boluses do not control seizures, then other measures should be instituted. A number of options are included below, although diazepam or lorazepam are used most commonly. Diazepam — Intravenously administered diazepam (0.1 to 0.3 mg/kg over 60 seconds, maximum cumulative dose 20 mg) rapidly enters the central nervous system, where it


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achieves anticonvulsant levels within one minute, and will control seizures in greater than 80 percent of patients within five minutes [34]. A diazepam gel for rectal administration is also available (0.2 mg/kg). Some experts recommend avoiding benzodiazepines for management of eclamptic seizures because of potentially profound depressant effects on the fetus and mother. This effect becomes clinically significant when the total maternal dose of diazepam exceeds 30 mg. Because of subsequent redistribution of the drug into adipose tissue, the duration of diazepam's acute anticonvulsant effect is typically less than 20 minutes. Lorazepam 0.02 to 0.03 mg/kg intravenously, allowing approximately one minute to assess its effect. If seizures continue at this point, additional doses of lorazepam (up to a cumulative dose of 0.1 mg/kg) are infused at a maximum rate of 2 mg/minute for acute treatment. Lorazepam is as effective as diazepam in terminating seizures, but the time from its injection to its maximum effect against seizures is as long as two minutes. The clinical advantage of lorazepam is that the effective duration of action against seizures is as long as four to six hours because of its less pronounced redistribution into adipose tissue. Sodium amobarbital 250 mg intravenously over three to five minutes [10]. Treatment of status epilepticus is discussed in detail separately. (See "Status epilepticus in adults"). Delivery — Eclampsia is usually considered an absolute contraindication to expectant management, although this has been attempted [35]. The definitive treatment for eclampsia is prompt delivery; however, this does not necessarily preclude induction of labor [36,37]. After maternal stabilization, factors to consider in determining the mode of delivery are gestational age, Bishop score, whether the patient is in labor, and fetal condition and position. In general, fewer than one-third of women with severe preeclampsia/eclampsia remote from term (eg, less than 32 weeks of gestation) with an unfavorable cervix and not in labor will successfully deliver vaginally [25,38,39]. Cesarean delivery is a reasonable option for these women. However, the fetus benefits from in utero resuscitation before delivery; therefore, it is desirable to wait 15 to 20 minutes and until the mother and fetus show signs of recovery (control of convulsions; mother oriented to name, time, and place; fetal heart rate reassuring) before proceeding to surgery, if possible. Cervical ripening agents can be used to improve the Bishop score; however, in my opinion, long inductions should be avoided and a clear endpoint for delivery planned (eg, within 24 hours). (See "Induction of labor"). Anesthesia issues are the same as for women with preeclampsia. (See "Management of preeclampsia", section on Anesthesia). POSTPARTUM COURSE — Maternal vital signs, input, and output should be monitored closely to detect large changes in blood pressure and fluid imbalance. Seizures due to eclampsia always resolve postpartum, generally within a few hours to days. Diuresis (greater than 4 L/day) is believed to be the most accurate clinical indicator of resolution of preeclampsia/eclampsia, but is not a guarantee against the development of seizures [8]. Anticonvulsant drugs are generally administered for 24 to 48 hours postpartum, when the risk of recurrent seizures is low. The optimal duration of therapy has not been determined. Therapy is continued in women whose disease has not begun to improve postpartum and discontinued in women who are clearly improving clinically (eg, diuresis of ≥100 mL/h for two consecutive hours and the absence of symptoms). (See "Management of preeclampsia", section on Magnesium regimen). PROGNOSIS — A summary of the type and frequency of complications of eclampsia is shown in the table (show table 3).

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Maternal outcome — Maternal complications occur in up to 70 percent of women with eclampsia and include abruption placentae, disseminated intravascular coagulopathy, acute renal failure, hepatocellular injury, liver rupture, intracerebral hemorrhage, transient blindness, cardiorespiratory arrest, aspiration pneumonitis, acute pulmonary edema, and postpartum hemorrhage [25]. Hepatocellular damage, renal dysfunction, coagulopathy, hypertension, and neurologic abnormalities typically resolve following delivery. However, brain damage from hemorrhage or ischemia may result in permanent neurologic sequelae and is the most common cause of death in eclamptic women [40,41]. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) develops in approximately 10 to 20 percent of women with preeclampsia/eclampsia. Maternal mortality rates of 0 to 14 percent have been reported [4,14,42,53]. Maternal mortality and severe morbidity rates are lowest among women receiving regular prenatal care who are managed by experienced physicians in tertiary centers (maternal mortality 0 to 1.8 percent) [10,15,25,43,44,53]. The highest rates are in developing countries where prenatal, intrapartum, and neonatal care are compromised by limited resources [42,45]. This was illustrated by a large retrospective analysis of 990 cases of eclampsia in Mexico in which the overall maternal mortality rate was 13.9 percent (138/990) [42]. The subgroup of women with eclampsia prior to 28 weeks of gestation had the highest risk of maternal death (12/54 or 22 percent); multiple seizures outside of the hospital setting was another common cause of death. Perinatal outcome — Premature delivery, abruptio placenta, and intrauterine asphyxia are the primary causes of perinatal death in eclamptic pregnancies. Perinatal mortality ranges from 9 to 23 percent and is closely related to gestational age [4,42]. As an example, perinatal mortality in a series of 54 pregnant women with eclampsia prior to 28 weeks of gestation was 93 percent [42], but only 9 percent in another study in which the mean gestational age at birth was 32 weeks [46]. Recurrence risk — Recurrent eclampsia occurs in 2 percent of subsequent pregnancies [47,48]. The risk appears to be reduced by close maternal monitoring and timely intervention if preeclampsia develops [49]. Preeclampsia, however, cannot be prevented. (See "Prevention of preeclampsia"). The risk of recurrence was illustrated by a study that followed 159 nulliparous women with a history of eclampsia and no preexisting hypertension through 334 subsequent pregnancies [50]. The incidence of mild preeclampsia, severe preeclampsia, and eclampsia in these pregnancies was 13, 9, and 2 percent, respectively. The corresponding figures for the subset of women whose eclampsia occurred at ≤30 weeks of gestation in the index pregnancy were 17, 25, and 2 percent, respectively. Subsequent pregnancies in women with a history of severe preeclampsia or eclampsia are also at increased risk of other obstetric complications compared to women with no such history. These problems include [47,48,50,51]: Abruptio placenta (2.5 to 6.5 versus 0.4 to 1.3 percent of the general obstetrical population) Preterm delivery (15 to 21 versus 12 percent) Intrauterine growth restriction (12 to 23 versus 10 percent) Perinatal mortality (4.6 to 16.5 versus 1 percent). Women with a history of preeclampsia/eclampsia remote from term (less than 28 weeks of gestation) are at highest risk of developing these complications, as well as recurrent preeclampsia [50,51]. This risk appears to be the same whether they had severe preeclampsia or eclampsia. Long-term maternal prognosis — Chronic hypertension develops in 0 to 78 percent (mean 24 percent) of women with a history of preeclampsia/eclampsia [47,48,50-52]. The wide range reported in the literature is due to the influence of variables such as maternal age and duration of follow-up (the increased risk of subsequent hypertension only becomes apparent after an average follow-up of 10 years [48]). The risk appears to be highest in the subgroup of women who have subsequent


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hypertensive pregnancies, multiparas with eclampsia, and those with eclampsia remote from term [47,48,50]. Other long-term maternal risks are discussed elsewhere. (See "Clinical features, diagnosis, and long-term prognosis of preeclampsia", section on Prognosis). PREVENTION Can eclampsia be predicted? — The relationship between hypertension, signs and symptoms of cortical irritability (eg, headache that is usually severe or persistent, visual disturbances, nausea, vomiting, fever, hyperreflexia), and seizures remains unclear. The magnitude of blood pressure elevation does NOT appear to be predictive of eclampsia, although it correlates well with the incidence of stroke (show figure 1). Twenty to 38 percent of eclamptic patients have a maximal blood pressure less than 140/90 prior to their seizure and about 20 percent have no evidence of proteinuria [4,14,15]. The majority of eclamptic women have one or more antecedent symptoms in the hours prior to an eclamptic seizure. A retrospective analysis of 383 cases of eclampsia in the United Kingdom reported that 59 percent of eclamptic women experienced prodromal headache, visual disturbance (eg, scotomata, amaurosis, blurred vision, diplopia, homonymous hemianopsia), or epigastric pain [4]. Pregnant women should be aware that they should call their health care provider if these symptoms develop. This study also found that eclampsia was the first manifestation of pregnancy-related hypertensive disease in 38 percent of cases [4]. Similar findings were reported in studies from Sweden, Scotland, and the United States [54-56]. In one review of 179 consecutive cases, factors identified to be at least partially responsible for failure to prevent eclampsia were: physician error (36 percent), lack of prenatal care (19 percent), abrupt onset (18 percent), magnesium failure (13 percent), late postpartum onset (12 percent), and early onset before 21 weeks (3 percent) [55]. Therefore, many cases of eclampsia do not appear to be preventable, even among women receiving regular prenatal care, or those who are hospitalized. Prevention of the first eclamptic seizure in preeclamptic women — This topic is discussed in detail separately. (See "Management of preeclampsia", section on Anticonvulsants). SUMMARY AND RECOMMENDATIONS Summary Eclampsia refers to the occurrence of one or more generalized convulsions and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions. (See "Introduction" above). An eclamptic seizure occurs in 0.5 percent of mildly preeclamptic women and 2 percent of severely preeclamptic women. The incidence of eclampsia is 4 to 5 cases per 10,000 live births in developed countries. (See "Incidence and epidemiology" above). Just over one-third of cases occur at term, developing intrapartum or within 48 hours of delivery. (See "Timing in pregnancy" above). An eclamptic seizure is typically tonic-clonic and lasts 60 to 75 seconds. Symptoms that may occur before the seizure include persistent frontal or occipital headache, blurred vision, photophobia, right upper quadrant or epigastric pain, and altered mental status. In up to one-third of cases, there is no proteinuria or blood pressure is less than 140/90 mmHg prior to the seizure. (See "Clinical manifestations and diagnosis" above and see "Can eclampsia be predicted?" above). The goals of management are to stabilize the mother, prevent recurrent convulsions, treat severe hypertension to prevent cerebral hemorrhage, and initiate delivery of the fetus. (See "Management" above).


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The risk of recurrent eclampsia in a future pregnancy is 2 percent. (See "Recurrence risk" above). Recommendations For women with eclampsia, we recommend treatment with magnesium sulfate rather than other anticonvulsants (Grade 1A). Compared to phenytoin and diazepam, magnesium sulfate reduces the rate of recurrent seizures by one-half to two-thirds and reduces the rate of maternal death by one-third. (See "Treatment of convulsions" above). Given that intravascular administration has a faster therapeutic effect and is less painful than intramuscular administration, we suggest using an intravascular regimen (Grade 2C). We give a loading dose of magnesium sulfate 6 g intravenously over 15 minutes, followed by 2 to 3 g/hour administered as a continuous intravenous infusion. The loading dose may be given safely in the presence of renal insufficiency, but the maintenance dose should be omitted or reduced in this setting. The maintenance phase is given only if a patellar reflex is present (loss of deep tendon reflexes is the first manifestation of symptomatic hypermagnesemia), respirations are greater than 12 per minute, and urine output is over 100 mL in four hours. (See "Administration of magnesium sulfate" above). In women with severe hypertension, we administer hydralazine or labetalol to achieve a systolic pressure of 140 to 155 mmHg and diastolic pressure of 90 to 105 mmHg. (See "Treatment of hypertension" above). Delivery is the only curative treatment, but this does not necessarily preclude induction of labor. Cesarean delivery is a reasonable option for women less than 32 weeks of gestation who have an unfavorable cervix. After a seizure, we suggest waiting 15 to 20 minutes and until the mother and fetus show signs of recovery (control of convulsions; mother oriented to name, time, and place; fetal heart rate reassuring) before proceeding to surgery, if possible. (See "Delivery" above).

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REFERENCES 1.

American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. ACOG. Technical Bulletin #219. American College of obstetricians and Gynecologists, Washington, DC, 1996.

2.

www.cdc.gov.

3.

Sibai, BM. Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials. Am J Obstet Gynecol 2004; 190:1520.

4.

Douglas, KA, Redman, CW. Eclampsia in the United Kingdom. BMJ 1994; 309:1395.

5.

Tuffnell, DJ, Jankowicz, D, Lindow, SW, et al. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG 2005; 112:875.

6.

Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol 1988; 158:80.

7.

Lubarsky, SL, Barton, JR, Friedman, SA, et al. Late postpartum eclampsia revisited. Obstet Gynecol 1994; 83:502.

8.

Miles, JF Jr, Martin, JN Jr, Blake, PG, et al. Postpartum eclampsia: a recurring perinatal dilemma. Obstet Gynecol 1990; 76:328.

9.

Chames, MC, Livingston, JC, Ivester, TS, Barton, JR. Late postpartum eclampsia: A preventable disease?. Am J Obstet Gynecol 2002; 186:1174.

10.

9 de 19

Sibai, BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005; 105:402.


Eclampsia

10 de 19

11.

Morriss, MC, Twickler, DM, Hatab, MR, et al. Cerebral blood flow and cranial magnetic resonance imaging in eclampsia and severe preeclampsia. Obstet Gynecol 1997; 89:561.

12.

Sheehan, HL, Lynch, JB. Pathology of toxaemia of pregnancy. William and wilkins, Baltimore, 1973.

13.

Zeeman, GG, Fleckenstein, JL, Twickler, DM, Cunningham, FG. Cerebral infarction in eclampsia. Am J Obstet Gynecol 2004; 190:714.

14.

Sibai, BM, McCubbin, JH, Anderson, GD, et al. Eclampsia. I. Observations from 67 recent cases. Obstet Gynecol 1981; 58:609.

15.

Sibai, BM. Eclampsia. VI. Maternal-perinatal outcome in 254 consecutive cases. Am J Obstet Gynecol 1990; 163:1049.

16.

Dahmus, MA, Barton, JR, Sibai, BM. Cerebral imaging in eclampsia: Magnetic resonance imaging versus computed tomography. Am J Obstet Gynecol 1992; 167:935.

17.

Paul, RH, Koh, KS, Bernstein, SG. Changes in fetal heart rate-uterine contraction patterns associated with eclampsia. Am J Obstet Gynecol 1978; 130:165.

18.

Hinchey, J, Chaves, C, Appignani, B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:494.

19.

Lewington, S, Clarke, R, Qizilbash, N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903.

20.

Lindenstrom, E, Boysen, G, Nyboe, J. Influence of systolic and diastolic blood pressure on stroke risk: a prospective observational study. Am J Epidemiol 1995; 142:1279.

21.

Working group report on high blood pressure in pregnancy. National Institutes of Health, Washington, DC 2000.

22.

Sibai, BM. Treatment of hypertension in pregnant women. N Engl J Med 1996; 335:257.

23.

von Dadelszen, P, Ornstein, MP, Bull, SB, et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000; 355:87.

24.

Magee, LA, Ornstein, MP, von Dadelszen, P. Fortnightly review: management of hypertension in pregnancy. BMJ 1999; 318:1332.

25.

Pritchard, JA, Cunningham, FG, Pritchard, SA. The Parkland Memorial Hospital protocol for treatment of eclampsia: evaluation of 245 cases. Am J Obstet Gynecol 1984; 148:951.

26.

Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345:1455.

27.

Duley, L, Gulmezoglu, AM. Magnesium sulphate versus lytic cocktail for eclampsia (Cochrane Review). Cochrane Database Syst Rev 2001; 1:CD002960.

28.

Duley, L, Henderson-Smart, D. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev 2003; :CD000127.

29.

Duley, L, Henderson-Smart, D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev 2003; :CD000128.

30.

Belfort, MA, Moise, KJ Jr. Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol 1992; 167:661.

31.

Gerthoffer, WT, Shafer, PG, Taylor, S. Selectivity of phenytoin and dihydropyridine calcium channel blockers for relaxation of the basilar artery. J Cardiovasc Pharmacol 1987; 10:9.

32.

American College ofObstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia. ACOG practice bulletin #33. American College of Obstetricians and Gynecologists, 2002.

33.

Sibai, BM, Lipshitz, J, Anderson, GD, Dilts, PV Jr. Reassessment of intravenous MgSO4 therapy in preeclampsia-eclampsia. Obstet Gynecol 1981; 57:199.

34.

Delgado-Escueta, AV, Wasterlain, C, Treiman, DM, Porter, RJ. Current concepts in neurology: management of status epilepticus. N Engl J Med 1982; 306:1337.

35.

Andersen, WA, Harbert, GM Jr. Conservative management of pre-eclamptic and eclamptic patients: a re-evaluation. Am J Obstet Gynecol 1977; 129:260.

36.

American College of Obstetricians and Gynecologists. Induction of labor. ACOG practice bulletin #10. American College of Obstetricians and Gynecologists, Washington, DC 1999.

37.

Tukur, J, Umar, NI, Khan, N, Musa, D. Comparison of emergency caesarean section to


Eclampsia misoprostol induction for the delivery of antepartum eclamptic patients: a pilot study. Niger J Med 2007; 16:364.

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38.

Alexander, JM, Bloom, SL, McIntire, DD, Leveno, KJ. Severe preeclampsia and the very low birth weight infant: is induction of labor harmful?. Obstet Gynecol 1999; 93:485.

39.

Nassar, AH, Adra, AM, Chakhtoura, N, et al. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 1998; 179:1210.

40.

Sibai, BM, Spinnato, JA, Watson, DL, et al. Eclampsia. IV. Neurological findings and future outcome. Am J Obstet Gynecol 1985; 152:184.

41.

Okanloma, KA, Moodley, J. Neurological complications associated with the pre-eclampsia/eclampsia syndrome. Int J Gynaecol Obstet 2000; 71:223.

42.

L贸pez-Llera, M. Main clinical types and subtypes of eclampsia. Am J Obstet Gynecol 1992; 166:4.

43.

Conde-Agudelo, A, Kafury-Goeta, AC. Case-control study of risk factors for complicated eclampsia. Obstet Gynecol 1997; 90:172.

44.

MacKay, AP, Berg, CJ, Atrash, HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001; 97:533.

45.

Moodley, J. Maternal deaths due to hypertensive disorders in pregnancy: Saving Mothers report 2002-2004. Cardiovasc J Afr 2007; 18:358.

46.

Sibai, BM, ANderson, GD, Abdella, TN, et al. Eclampsia. III. Neonatal outcome, growth, and development. Am J Obstet Gynecol 1983; 146:307.

47.

Chesley, LC, Annitto, JE, Cosgrove, RA. The remote prognosis of eclamptic women. Am J Obstet Gynecol 1976; 124:446.

48.

Sibai, BM, el-Nazer, A, Gonzalez-Ruiz, A. Severe preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. Am J Obstet Gynecol 1986; 155:1011.

49.

Gilstrap LC, 3rd, Cunningham, FG, Whalley, PJ. Management of pregnancy-induced hypertension in the nulliparous patient remote from term. Semin Perinatol 1978; 2:73.

50.

Sibai,BM, Sarinoglu, C, Mercer, BM. Eclampsia. VII. Pregnancy outcome after eclampsia and long-term prognosis. Am J Obstet Gynecol 1992; 166:1757.

51.

Sibai, BM, Mercer, B, Sarinoglu, C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am J Obstet Gynecol 1991; 165:1408.

52.

Sibai, BM, Ramadan, MK, Chari, RS, Friedman, SA. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995; 172:125.

53.

Zwart, JJ, Richters, A, Ory, F, et al. Eclampsia in the Netherlands. Obstet Gynecol 2008; 112:820.

54.

Moller, B, Lindmark, G. Eclampsia in Sweden, 1976-1980. Acta Obstet Gynecol Scand 1986; 65:307.

55.

Sibai, BM, Abdella, TN, Spinnato, JA, et al. Eclampsia. V. The incidence of nonpreventable eclampsia. Am J Obstet Gynecol 1986; 154:581.

56.

Campbell, DM, Templeton, AA. Is eclampsia preventable? In: Bonnar, J, MacGillivray, I, Symonds, ED (eds). Pregnancy Hypertension, University Park Press, Baltimore, 1980, p483.


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GRAPHICS Criteria for severe preeclampsia New onset proteinuric hypertension and at least one of the following:

Symptoms of central nervous system dysfunction: Blurred vision, scotomata, altered mental status, severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and progresses despite analgesic therapy

Symptoms of liver capsule distention: Right upper quadrant or epigastric pain Nausea, vomiting

Hepatocellular injury: Serum transaminase concentration at least twice normal

Severe blood pressure elevation: Systolic blood pressure

160 mm Hg or diastolic

110 mm Hg on two occasions at least six hours apart

Thrombocytopenia: Less than 100,000 platelets per cubic millimeter

Proteinuria: 5 or more grams in 24 hours

Oliguria <500 mL in 24 hours Severe fetal growth restriction Pulmonary edema or cyanosis Cerebrovascular accident Based on Diagnosis and Management of Preeclampsia and Eclampsia. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin #33, January 2002 and Working Group Report on High Blood Pressure in Pregnancy. National Instititutes of Health, Washington, DC 2000


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Risk factors for the development of preeclampsia Nulliparity Preeclampsia in a previous pregnancy Age >40 years or <18 years Family history of preeclampsia Chronic hypertension Chronic renal disease Antiphospholipid antibody syndrome or inherited thrombophilia Vascular or connective tissue disease Diabetes mellitus (pregestational and gestational) Multifetal gestation High body mass index Male partner whose mother or previous partner had preeclampsia Hydrops fetalis Unexplained fetal growth restriction Woman herself was small for gestational age Fetal growth restriction, abruptio placentae, or fetal demise in a previous pregnancy Prolonged interpregnancy interval Smoking decreases the risk of preeclampsia


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Phases of tonic-clonic seizures Aura (None) Tonic phase (10 to 20 seconds)

Sudden loss of consciousness Loss of posture with high risk of self injury depending on activity Brief flexion of arms, eyes deviated upward Extension of back, neck, arms, and legs Involuntary crying out from contraction of respiratory muscles Shallow respiration, cyanosis may occur Ends with tremors which gradually slow and merge with clonic phase Clonic phase (30 to 90 seconds)

Brief, violent, generalized flexor contractions alternating with progressively longer muscle relaxation Cyanosis Possible cheek or tongue biting Foamy salivation Possible loss of bowel or bladder control Ends with deep inspiration, sustained muscle relaxation Postictal phase (Minutes to several hours)

Headache, mild confusion Muscles sore Fatigue, patient may sleep and awake refreshed Other features

Fast heart rate Elevated blood pressure Respiratory and metabolic acidosis Dilated pupils Risk of vertebral fracture, pneumonia

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Stroke mortality related to blood pressure and age

Stroke mortality rate, pictured on a log scale with 95 percent confidence intervals, in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of that decade. Stroke mortality increases with both higher pressures and older ages. For diastolic pressure, each age-specific regression line ignores the left-hand point (ie, at slightly less than 75 mmHg), for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg). Data from Prospective Studies Collaboration, Lancet 2002; 360:1903.


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Summary of maternal and neonatal outcomes

Outcome Abruption Disseminated intravascular coagulation Pulmonary edema Acute renal failure Aspiration pneumonia Cardiopulmonary arrest Liver hematoma HELLP syndrome Perinatal death Preterm birth Adapted from: Sibai, BM. Obstet Gynecol 2005; 105:402.

Frequency, percent 7 to 10 7 to 11 3 to 5 5 to 9 2 to 3 2 to 5 1 10 to 15 5.6 to 11.8 50


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Grade 1A recommendation A Grade 1A recommendation is a strong recommendation, and applies to most patients in most circumstances without reservation. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present. Explanation:

A Grade 1 recommendation is a strong recommendation. It means that we believe that if you follow the recommendation, you will be doing more good than harm for most, if not all of your patients. Grade A means that the best estimates of the critical benefits and risks come from consistent data from well-performed, randomized, controlled trials or overwhelming data of some other form (eg, well-executed observational studies with very large treatment effects). Further research is unlikely to have an impact on our confidence in the estimates of benefit and risk. Recommendation grades 1. Strong recommendation: Benefits clearly outweigh the risks and burdens (or vice versa) for most, if not all, patients 2. Weak recommendation: Benefits and risks closely balanced and/or uncertain Evidence grades A. High-quality evidence: Consistent evidence from randomized trials, or overwhelming evidence of some other form B. Moderate-quality evidence: Evidence from randomized trials with important limitations, or very strong evidence of some other form C. Low-quality evidence: Evidence from observational studies, unsystematic clinical observations, or from randomized trials with serious flaws For a complete description of our grading system, please see the UpToDate editorial policy which can be found by clicking "About UpToDate" and then selecting "Policies".


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Grade 2C recommendation A Grade 2C recommendation is a very weak recommendation; other alternatives may be equally reasonable. Explanation:

A Grade 2 recommendation is a weak recommendation. It means "this is our suggestion, but you may want to think about it." It is unlikely that you should follow the suggested approach in all your patients, and you might reasonably choose an alternative approach. For Grade 2 recommendations, benefits and risks may be finely balanced, or the benefits and risks may be uncertain. In deciding whether to follow a Grade 2 recommendation in an individual patient, you may want to think about your patient's values and preferences or about your patient's risk aversion. Grade C means the evidence comes from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain. Recommendation grades 1. Strong recommendation: Benefits clearly outweigh the risks and burdens (or vice versa) for most, if not all, patients 2. Weak recommendation: Benefits and risks closely balanced and/or uncertain Evidence grades A. High-quality evidence: Consistent evidence from randomized trials, or overwhelming evidence of some other form B. Moderate-quality evidence: Evidence from randomized trials with important limitations, or very strong evidence of some other form C. Low-quality evidence: Evidence from observational studies, unsystematic clinical observations, or from randomized trials with serious flaws For a complete description of our grading system, please see the UpToDate editorial policy which can be found by clicking "About UpToDate" and then selecting "Policies".


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Eclampsia