Pre-eclampsia affects up to 7% of pregnancies and <1% of these women develop EC [10]. Approximately 1 in 50 women experiencing eclamptic seizures will die annually from complications [11]. In a prospective survey of EC in the United Kingdom (UK), the incidence of EC was 4.9/1000 [12]. The leading cause of death with PREC-EC patients is cerebrovascular accidents particularly intracerebral hemorrhages. The mortality rate ranges from 2 to 24%. Table 16.2 summarizes the specific causes of death associated with EC and PREC. The case fatality in women with eclampsia is 71 per 10,000 [9]. Although the incidence of PREC has not changed significantly over the past 6 decades, the rate of major complications from the disease has been on a marked decline [13].

Several risk factors for EC have been identified. Those include prima gravidity, lack of prenatal care, urinary tract infections, family history, diabetes mellitus, multiple gestation, extremes of age, obesity, black ethnicity, preexisting hypertension, vascular renal disease, prolonged labor, and hydatidiform moles [10, 14].

To date, the underlying pathophysiology of EC is still not fully elucidated but vascular endothelial damage or dysfunction appears to be the common pathological feature in the placenta, kidneys, and brain [15]. A recent hypothesis by Odent [16] proposed that PREC could be the result of maternal-fetal conflict . The developing fetal brain requires EPA, a long chain n-3 polyunsaturated fatty acid. The theory suggests that the fetus need for EPA override the maternal need. A decrease in maternal EPA in PREC and EC women as compared to their normotensive counterparts appears to play a role in the development of this condition [16]. Other mechanisms suggested for eclamptic convulsions include cerebral vasospasm, hemorrhage or edema, metabolic or hypertensive encephalopathy [17].

By definition, EC is characterized by the presence of seizures. They can occur before, during, or after labor [18]. Antepartum EC refers to the onset of seizures before the start of labor. Intrapartum EC refers to seizures that occur during labor, and postpartum EC is the occurrence of seizures within 7 days of delivery of the fetus and placenta. Two percent of EC occur more than 7 days past delivery [19]. In some women seizures can occur as late as 11 days [20]. In the USA, 53% of women had antepartum seizures, 36% intrapartum seizures, and 11% postpartum seizures [19]. In the UK 38% had antepartum seizures, 18% intrapartum seizures, and 44% postpartum eclampsia [12].

The syndrome may also be associated with headaches, visual complaints, epigastric pain, oliguria, depression of consciousness, thrombocytopenia, fetal growth retardation, and elevated liver enzymes.

Abnormal EEGs are reported with PREC [21]. Diffuse slow activity (theta or delta waves) sometimes with focal slow activity is usually found on EEG [21]. Paroxysmal spike activity has been reported but this is not pathognomonic of PREC as similar patterns are found in other conditions [21]. No correlation was found between EEG abnormalities and the degree of maternal arterial blood pressure [21].

The radiological features found in EC patients are certainly not unique. Diffuse cerebral edema [22], hemorrhages [23], and infarcts [24] have been demonstrated in patients with EC using computed tomography (CT) scan. Magnetic resonance image (MRI) studies of brain of EC patients revealed focal changes characteristic of ischemia [25]. MRI features consistent with reversible posterior leukoencephalopathy have also been reported [26].

Early detection remains the mainstay of treatment in EC patients. The best treatment for PREC and EC is delivery. If delivery is not possible, then management of the patient should include hospitalization, close observation, and seizure prophylaxis until delivery can safely be performed. In a review of obstetric patients admitted to a medical-surgical ICU in a large tertiary referral center over a 5-year period PREC was the single most common diagnosis representing 22 percent of all patients [27].

Over the last two decades magnesium has emerged as the drug of choice for preventing eclampsia . Large randomized trials and systematic reviews have shown the usefulness of magnesium sulfate in treating recurrent eclamptic seizures and in the prophylaxis of EC [28, 29].

In 1995 the Eclampsia Trial Collaborative Group showed unequivocally that magnesium given intramuscularly or intravenously is superior to phenytoin or diazepam in reducing recurrent eclamptic seizures [29]. This international multicenter randomized study included 1687 women with EC. The women allocated to magnesium sulfate therapy had a 52% (95% C.l. 64% to 37%) reduction in incidence of recurrent seizures compared to those given diazepam (13.2% vs. 27.9%). Maternal and perinatal morbidity were comparable between the two groups. In a second comparison between magnesium sulfate and phenytoin, the women randomized to receive magnesium sulfate had a 67% (95% C.I. 79–97%) reduced incidence of recurrent seizures (5.7% vs. 17.1%). Maternal mortality was non-significantly lower in the magnesium group compared with the phenytoin group [26]. Women who received magnesium were also less likely to be ventilated when compared to phenytoin (14.9% vs. 22.5%). The women in the magnesium group were also less likely to develop pneumonia (3.9% vs. 8.8%) and be less likely to be admitted to the ICU (16.7% vs. 25.1%) when compared to phenytoin.

The Magpie study, another randomized placebo-controlled trial, was designed to assess the value of magnesium for prophylaxis in EC [30]. The study included 10,000 women with PREC who were randomized to receive magnesium sulfate before or during labor, or after giving birth [30]. Magnesium was effective in reducing seizures 58% (95% C.I. 40–71%). Treatment was also safe for the neonate in this setting, and without any excess of serious maternal morbidity. Of the 5055 women who were randomized in the magnesium and the placebo groups 46 (0.9%) had respiratory depression and 5 (0.1%) had respiratory arrest in the magnesium group compared to 27 (0.5%) and 2 (0.04%) in the placebo group, respectively [30]. Respiratory arrest was responsible for one death in each group. 14 (0.3%) developed pneumonia in the magnesium group compared to 6 (0.1%) in the placebo group [30].

Another multicenter randomized unblinded study compared magnesium to calcium channel blocker nimodipine, a cerebral vasodilator to prevent EC [30]. PREC women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (2.6% vs. 0.8%, p = 0.01). The antepartum risk for EC did not differ between the two treatment arms, but the nimodipine arm had a higher risk of postpartum seizures (1.1% vs. 0%, p = 0.01). Neonatal outcomes did not differ between the two groups [30].

Similar results were reported in a Cochrane review analysis that included published randomized studies between magnesium and placebo or anti-epileptics [29]. The reviewers concluded from six studies that magnesium sulfate more than halves the risk of eclampsia, and probably reduces the risk of maternal death. A quarter of women had side effects, particularly flushing. Risk of placental abruption was reduced for women allocated magnesium sulfate (RR 0.64, 95% C.l. 0.5–0.8). Women allocated to magnesium sulfate had a small non-significant increase (5%) in the risk of caesarean section. Magnesium sulfate was better than phenytoin and nimodipine in reducing the risk of eclampsia, but with an increased risk of caesarean section (RR I.2, 95% C.I. 1.05–1.4). The summary of the Cochrane review is detailed in Table 16.3.

The most commonly used magnesium protocol in EC is 4–6 g IV bolus over 5 min, followed by 1–2 g/h IV infusion for at least 48 hours postpartum. If the treatment is used prophylactically in PREC, it can be stopped after 24 h [10]. Half this dose should be used in patients with serum creatinine more than 1.3 mg/dL [10].

Patients should be admitted to an intensive care unit and be monitored closely, particularly respirations, patellar reflexes, and urine output. Magnesium is known to affect the neuromuscular junction but it should not have any deleterious effect on a patient’s mental status. If patellar reflexes are lost the next magnesium dose should be held and the magnesium level should be checked. It may be restarted at a lower dose when the reflexes return if still desired. If the urine output falls below 25 cc/hr., then the rate of infusion of magnesium or the IM dose should be cut into half. In case of respiratory depression or arrest the patient airway must be first secured (by endotracheal intubation if needed) and one gram of calcium gluconate (10% solution) should be administered IV.

In patients with refractory seizures several anticonvulsant regimens can be used. An additional dose 1–2 g IV of Mg can be given or a loading dose of phenytoin (18 mg/kg IV at a maximum rate of 50 mg/min) can be tried. A dark room with low noise, padded bed nails, and continuous fetal monitoring are additional measures.

Pritchard et al. first described the association between coagulation and liver enzymes abnormalities with PREC [31]. In 1982, Weinstein coined this syndrome of hemolysis (anemia, increase bilirubin schistocytes in blood smear), elevated liver enzymes, and a low platelet count (<100,000/mm³), as the HELLP syndrome [32]. It complicates up to 10% of eclamptic cases [17, 33]. Mortality resulting from HELLP syndrome ranges from 2 to 24% of cases [9]. Management of seizures in patients with HELLP syndrome is similar to EC patients. Magnesium should be initiated at seizure onset. Although no specific data exist regarding seizures, antepartum administration of corticosteroids (dexamethasone 10 mg every 13 h until delivery) has been shown in randomized trials to stabilize and improve the laboratory values and clinical status of the mother and potentially the fetus [34]. The increase in liver enzymes may limit the use of some anticonvulsants such as phenytoin, carbamazepine, and or valproic acid. Levetiracetam (Keppra©) may be used as a second line agent or as a second agent if magnesium failed to stop the seizures. Keppra can be started as 500 mg P0 given every 12 h and may be increased to a maximum dose of 3000 mg/day. If patients develop status epilepticus, then phenobarbital or pentobarbital can be used as a therapeutic option. More details regarding treatment of seizures in patients with liver dysfunction can be found in the chapters on Treatment of Critical Care Seizures and SE.

Hypertensive encephalopathy (HE) is a complex cerebral disorder that is associated with a variety of conditions in which systemic BP rises acutely. The term was first coined by Oppenheimer and Fishberg in 1928 [35] and is defined as generalized or focal cerebral dysfunction that either partially or completely reverses with antihypertensive treatment [36].