Eclampsia

For patient information, click here

Overview
Eclampsia, an acute and life-threatening  complication of pregnancy,  is  characterized by the appearance of tonic-clonic seizures in a patient who had developed  preeclampsia;  rarely  does eclampsia  occur without  preceding  preeclamptic symptoms. Hypertensive disorder of pregnancy and toxemia of pregnancy are terms used to encompass both preeclampsia and eclampsia. Seizures and coma that happen during pregnancy but are due to preexisting or organic brain disorders are not eclampsia.

The term is derived from the Greek and refers to a flash, a term used by Hippocrates to designate a fever of sudden onset.

Prevalence
Eclampsia is a leading cause of maternal and perinatal mortality. The prevalence of eclampsia is reported to be 0.56 per 1,000 births (US data from 1979-86) versus 26 per 1,000 births for pre-eclampsia. While mortality can be kept low when antenatal care and maternal-fetal services are provided, mortality rates are substantial in challenging settings. Thus in a setting in India, maternal mortality and perinatal mortality were reported to be 32% and 39%, respectively, in 1993.

Eclamptic convulsions may appear in the last trimester (rarely before), during labour, and in the first two days postpartum; it would be highly unusual to see eclampsia later than 48 hours after delivery.

Risk factors
Eclampsia, like preeclampsia, tends to occur more commonly in first pregnancies and young mothers where it is  thought that exposure to paternal antigens still has been low. Further, women with preexisting vascular diseases (hypertension, diabetes, and nephropathy) or thrombophilic diseases such as the antiphospholipid syndrome are at higher risk to develop preeclampsia and eclampsia. Conditions with a large placenta (multiple gestation, hydatiform mole) also predispose for toxemia. Further, there is a genetic component; patients whose mother or sister had the condition are at higher risk. Patients with eclampsia are at increased risk for preeclampsia-eclampsia in a later pregnancy.

Pathophysiology
While multiple theories have been proposed to explain preeclampsia and eclampsia, it occurs only in the presence of a placenta and is resolved by its removal. E. W. Page suggested that placental hypoperfusion is a key feature of the process. It is accompanied by increased sensitivity of the maternal vasculature to pressure agents leading to vasospasm and hypoperfusion of multiple organs. Further, an activation of the coagulation cascade leads to microthombi formation and aggravates the perfusion problem. Loss of plasma from the vascular tree with the resulting edema additionally compromises the situation. These events lead to signs and symptoms of toxemia including hypertension, renal, pulmonary, and hepatic dysfunction, and - in eclampsia specifically - cerebral dysfunction. Preclinical markers of the disease process are signs of increased platelet and endothelial activation

Placental hypoperfusion is linked to abnormal modeling of the fetal-maternal interface that may be immunologically mediated  The invasion of the trophoblast appears to be incomplete. Adrenomedullin, a potent vasodilator, is produced in diminished quantities by the placenta in preeclampsia (and thus eclampsia). Other vasoactive agents are at play including prostacyclin, thromboxane A2, nitric oxide, and endothelins leading to vasoconstriction. Many studies have suggested the importance of a woman's immunological tolerance to her baby's father, whose genes are present in the young fetus and its placenta and which may pose a challenge to her immune system.

Eclampsia is seen as form of a hypertensive encephalopathy in the context of those pathological events that lead to preeclampsia. It is thought that cerebral vascular resistance is reduced, leading to increased blood flow to the brain. In addition to abnormal function of the endothelium, this leads to cerebral edema. Typically an eclamptic seizure will not lead to lasting brain damage; however, intracranial hemorrhage may occur.

Histopathology


Signs and symptoms
Typically patients show signs of pregnancy-induced hypertension and proteinuria prior to the onset of the hallmark of eclampsia, the  eclamptic convulsion. Other cerebral signs may precede the convulsion such as nausea, vomiting, headaches, and cortical blindness. In addition, with the advancement of the pathophysiological process, other organ symptoms may be present including abdominal pain, liver failure, signs of the HELLP syndrome, pulmonary edema, and oliguria. The fetus may have been already compromised by intrauterine growth retardation, and with the toxemic changes during eclampsia may suffer fetal distress. Placental bleeding and placental abruption may occur.

The eclamptic seizure
Chesley distinguishes these four stages of an eclamptic event: In the stage of invasion facial twitching can be observed around the mouth. In the stage of contraction tonic contractions render the body rigid; this stage may last about 15 to 20 seconds. The next stage is the stage of convulsion when involuntary and forceful muscular movements occur, the tongue may be bitten, foam appears at the mouth. The patient stops breathing and becomes cyanotic; this stage lasts about one minute. The final stage is a more or less prolonged coma. When the patient awakens, she is unlikely to remember the event. In some rare cases there are no convulsions and the patient falls directly into a coma. Some patients when they awake from the coma may have temporary blindness.

During a seizure, the fetus may experience bradycardia.

Differential diagnosis
Seizures during pregnancy that are unrelated to preeclampsia need to be distinguished from eclampsia. Such disorders include seizure disorders as well as brain tumor, aneurysm of the brain, medication- or drug-related seizures. Usually the presence of the signs of severe preeclampsia that precede and accompany eclampsia facilitate the diagnosis.

Treatment
The treatment of eclampsia requires prompt intervention and aims to prevent further convulsions, control the elevated blood pressure and deliver the fetus.

Prevention of convulsions
Prevention of convulsion is usually done using magnesium sulfate (4-6 g loading dose in 100 ml iv fluid given over 15-20 minutes, then 2g per hour as a continuous infusion) Evidence for the use of magnesium sulfate came from the international MAGPIE study.

Antihypertensive management
Antihypertensive management at this stage in pregnancy may consist of hydralazine (5-10 mg IV every 15-20 min until desired response is achieved) or labetalol (20 mg bolus iv followed by 40 mg if necessary in 10 minutes; the 80 mg every 10 up to maximum of 220 mg).

Delivery
If the woman has not yet been delivered, steps need to be taken to stabilize the patient and deliver her speedily. This needs to be done even if the fetus is immature as the eclamptic condition is unsafe for fetus and mother. As eclampsia is a manifestation of a multiorgan failure, other organs (liver, kidney, clotting, lungs, and cardiovascular system) need to be assessed in preparation for a delivery, often  a cesarean section, unless the patient is already in advanced labor. Regional anesthesia for cesarean section is contraindicated when a coagulopathy has developed.

Invasive hemodynamic monitoring
Invasive hemodynamic monitoring may be useful in eclamptic patients with severe cardiac disease, renal disease, refractory hypertensionpulmonary edema, and oliguria.

Prevention
Detection and management of preeclampsia is critical to reduce the risk of eclampsia. Appropriate management of patients with preeclampsia generally involves the use of magnesium sulfate as an agent to prevent convulsions, and thus preventing eclampsia.