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Preeclampsia and eclampsia
Background: Preeclampsia/eclampsia is a complex hypertensive disorder of pregnancy affecting multiple systems. The nervous system is commonly affected and is a cause of significant morbidity and death in these women.
Preeclampsia and eclampsia are not distinct disorders but are differentiated according to their clinical symptoms. The mildest disorder in this continuum is pregnancy-induced hypertension (PIH). In preeclampsia, hypertension and proteinuria are present, and when convulsions occur in addition to these signs, the condition is referred to as eclampsia. Although seizures define the condition of eclampsia, other neurologic findings may be observed earlier in the continuum of PIH/preeclampsia/eclampsia. The progression from mild PIH to preeclampsia and eclampsia may not occur in all women. In a prospective study at the author's center, as many as 28% of the women with a diagnosis of eclampsia did not have a diagnosis of preeclampsia prior to seizures.
The hypertensive disorders of pregnancy can be classified as follows:
- Pregnancy-induced hypertension is hypertension that develops as a consequence of pregnancy and regresses postpartum. It is classified into 3 types: (1) hypertension without proteinuria or pathological edema; (2) preeclampsia with proteinuria and/or pathological edema, which can be mild or severe; and (3) eclampsia with proteinuria and/or pathological edema along with convulsions
- Coincidental hypertension is chronic underlying hypertension that precedes pregnancy or persists postpartum.
- Pregnancy-aggravated hypertension is underlying hypertension worsened by pregnancy (ie, superimposed preeclampsia and superimposed eclampsia).
- Transient hypertension develops after the second trimester of pregnancy and is characterized by mild elevation of blood pressure that does not compromise the pregnancy. This form of hypertension regresses after delivery but may return in subsequent gestations.
Notably, these definitions do not use any values of blood pressure as a guideline. No consensus exists on the blood pressure values for diagnosing PIH. In general, when the blood pressure is 140/90 mm Hg or greater, the diagnosis of PIH is made. Some authors accept a rise of 15 mm Hg in diastolic and 30 mm Hg in systolic blood pressure from the baseline as diagnostic of PIH.
Pathophysiology: As mentioned above, preeclampsia/eclampsia is a multisystem disorder. The cardiovascular system is routinely involved, with hemodynamic changes resulting from severe hypertension that may lead to cardiac failure or pulmonary edema. The kidneys also are commonly affected, with resultant proteinuria and decreased glomerular filtration rate, which may lead to acute tubular necrosis and renal failure in severe cases. Hematologic changes related to the consumption of platelets and clotting factors resulting in intravascular coagulation may occur, at times associated with evidence of intravascular erythrocyte destruction. Abnormal liver function test results with elevation of liver enzymes can be observed commonly, but in rare instances, spontaneous hepatic rupture may ensue. Involvement of the brain may cause convulsions, coma, altered mental status, cortical blindness, and other manifestations of focal brain dysfunction.
The exact etiology of preeclampsia/eclampsia is not known. Current thinking is that the problem starts with the placenta. Fetal or uterine participation apparently are not crucial because this condition is identified in abdominal pregnancy and hydatidiform mole. In women with toxemia, the trophoblastic implantation is abnormal, resulting in lower placental perfusion. This in turn induces endothelial cell injury through unknown mediators. This leads to widespread vasospasm, and this vasospasm is considered to be central to the condition. Vasospasm leads to increased resistance to blood flow with resultant hypertension. This may also induce further endothelial damage and leakage of platelets and fibrinogen into the subendothelial space. These changes ultimately lead to surrounding tissue hypoxia, resulting in necrosis or hemorrhage in multiple end organs.
Usually, pregnant women develop marked reduction in peripheral vascular resistance. They also develop refractoriness to infused vasopressors, such as angiotensin II. These hemodynamic changes are reversed in preeclampsia/eclampsia. This may be due to decreased vascular responsiveness mediated, in part, by vascular endothelial synthesis of prostaglandins or similar substances. Decreased production of prostacyclin and increased synthesis of thromboxane-A2 in PIH may result in vasoconstriction. In addition, decreased production or release of nitric oxide, a potent vasodilator, may contribute to the development of or aggravate the preeclampsia/eclampsia syndrome.
Frequency:
- In the US : The incidence of preeclampsia is about 5% of pregnancies; the range is 5-10%. The incidence of eclampsia is considered to be about 5-7 per 10,000 deliveries.
- Internationally: The incidence of preeclampsia and eclampsia in the developed countries of North America and Europe is similar to those of the United States . On the other hand, incidence of eclampsia in developing nations varies widely, ranging from 1 per 100 to 1 per 1700 pregnancies.
Mortality/Morbidity:
- Although eclampsia is a rare complication of pregnancy, approximately 50,000 women worldwide are estimated to die annually because of eclampsia.
- The reported maternal mortality rate ranges from 1-20%.
- The perinatal mortality rate of neonates born to eclamptic mothers ranges from 1.3-3%.
Race:
- Preeclampsia/eclampsia syndrome is more common in blacks than in Hispanics.
- Hispanic women are more likely to be affected by this syndrome than white women.
- Higher incidences of the syndrome in the developing world may be related to racial differences, but effects of other environmental and social factors cannot be underestimated.
Age: Preeclampsia/eclampsia is more likely to occur in women at either extreme of reproductive life.
- A young nulliparous woman is more likely to experience the condition.
- Similarly, a multiparous woman older than 35 years is more likely to be affected.
- Other risk factors include multiple pregnancies, hydatidiform mole, and extrauterine pregnancy.
History: The discussion is restricted to the neurologic manifestations of preeclampsia/eclampsia syndrome. The syndrome of preeclampsia/eclampsia usually progresses in stages of worsening elevation of blood pressure, development of generalized edema, and headache followed by seizure; however, it can worsen very quickly, and a patient can develop serious neurologic and systemic complications in a matter of hours. On the other hand, some women may have seizures in the setting of moderate elevation of blood pressure without developing any other symptoms.
- Headache: The most common neurologic symptom in preeclampsia/eclampsia is headache; however, it is not an essential part of the clinical presentation. Headache can be bitemporal, frontal, occipital, or diffuse. Most women describe the headache as pulsating pain, but pain associated with feelings of pressure or sharp pain can also be present. The typical feature of the headache is that it is progressive and does not respond to routine over-the-counter remedies. In a minority of women, it is associated with photophobia or sonophobia, nausea, and rarely, vomiting. A new onset of progressive headache in a pregnant woman should alert her physician to the possibility of preeclampsia or eclampsia. Rarely, sudden explosive headache can occur and at times may be indicative of subarachnoid hemorrhage. A recent report has suggested that a small amount of subarachnoid hemorrhage over the cerebral convexity can occur in preeclampsia/eclampsia. However, it appears to carry a relatively benign long-term prognosis.
- Seizures: Convulsions are the other most common feature of this syndrome. Convulsions are the most common neurologic manifestation in eclampsia because the occurrence of convulsions confirms the diagnosis of eclampsia. Convulsions are usually generalized tonic-clonic in nature. Usually a brief single seizure occurs. Multiple seizures can also occur; however, status epilepticus is rare. Partial seizures or complex partial seizures can also occur. The seizures can occur prepartum, intrapartum, or postpartum. If the seizure occurs postpartum, it usually occurs within the first 24 hours after delivery; however, late postpartum eclamptic convulsions are by no means rare and have been reported as late as 23 days postpartum.
- Visual disturbances: Visual changes are common in preeclampsia/eclampsia. The most common symptom is blurring of vision. The visual disturbances are ominous and may indicate impending seizure. Blindness in women with eclampsia is rare and can be due to involvement of the occipital cortex or retina. Cortical blindness usually follows or heralds seizures. Again, it can occur in isolation without seizures. This demonstrates involvement of the brain in women with severe preeclampsia without seizure (ie, eclampsia). The blindness is usually transient and resolves completely within a few hours, but it may last longer. The other possibility is retinal detachment due to severe hypertension resulting in blindness; however, this is usually unilateral.
- Coma: Coma is a dreaded complication in eclampsia. Most women lapse into coma following a convulsion or repeated convulsions. Others may have not had a seizure prior to coma. Coma may be a result of intracerebral hemorrhage that, at times, may dissect into the ventricular system or over the surface of the brain, creating a massive subarachnoid hemorrhage. Coma can also follow a sudden rise in blood pressure, with resultant cerebral edema without hemorrhage.
- Symptoms of focal brain dysfunction: Other symptoms, such as hemiparesis and monoparesis, can also be observed in eclampsia if a region of the brain is malfunctioning. Other than cortical blindness, focal brain dysfunctions are rare.
- Other systemic symptoms: Preeclampsia/eclampsia is a systemic disorder, and nonneurologic symptoms are more common than neurologic symptoms in most women. Some women may be completely asymptomatic despite a markedly elevated blood pressure; however, they need to be monitored and cared for as carefully as other women with symptoms.
- Edema: Generalized edema is a common, but not an essential, feature of this syndrome. Swelling of feet and even hands is common in women during late pregnancy. Differentiating this edema from pathological edema is sometimes difficult. Edema of the hands and face should be regarded as pathological edema.
- Weight gain: Fluid retention is a physiologic consequence of pregnancy; however, excessive fluid retention in preeclampsia/eclampsia causes sudden gain in weight. This is again considered a warning sign for development of preeclampsia.
- Abdominal pain: The liver is commonly affected in this syndrome. Stretching of the capsule of the liver or ischemia results in pain in the right upper quadrant or epigastrium. Subcapsular hematoma or rupture of the liver may cause excessive pain in the area.
Physical: Physical examination is important in preeclampsia/eclampsia, both for diagnosis of the condition as well as for monitoring its progress and effects of the interventions.
- Blood pressure: Elevation of blood pressure is essential for the diagnosis of preeclampsia/eclampsia syndrome. Blood pressure of 140/90 mm Hg is accepted as high; however, relative hypertension can be difficult to define. Some authors have suggested that elevation of systolic blood pressure by 30 mm Hg and diastolic blood pressure by 15 mm Hg from baseline is also diagnostic of PIH, a requisite for the diagnosis of preeclampsia or eclampsia. In the majority of women with eclampsia, this is not an issue because the blood pressure elevation is extreme.
- Edema: Generalized edema is also common in this condition. Pitting edema of feet, legs, hands, and face can be observed. Nevertheless, women without edema may still have extremely high blood pressure or can experience seizures.
- Abdominal tenderness: Swelling of liver or liver ischemia can cause tenderness of the organ, as mentioned above.
- Neurologic examination: Findings of the neurologic examination are normal in most women or show only subtle abnormalities.
- Hyperreflexia: The most common finding on neurologic examination in women with eclampsia is hyperreflexia. However, differentiating this hyperreflexia from physiologic hyperreflexia observed in young individuals may be difficult. At times, the only way to diagnose the presence of hyperreflexia is by examining the woman later on and making the distinction retrospectively.
- Blindness: In cases of cortical blindness, the findings on eye examination are completely normal, including pupillary light reflex. The patient may develop denial of the blindness, known as Anton syndrome. Involvement of the parieto-occipital junction area may cause Balint syndrome (author's personal experience).
- Funduscopic examination: Funduscopic examination may reveal papilledema and vasoconstriction. In rare instances, it may show focal hemorrhage or retinal detachment.
- Focal neurologic findings: Depending on the extent of the brain involvement and location of the abnormalities, examination of the motor or sensory functions or deep tendon reflexes may reveal some abnormalities.
- Coma: Depending on the severity of the underlying brain involvement, the neurologic findings in a comatose patient vary. The patient may be completely unresponsive or may demonstrate posturing.
- Cognitive dysfunction: Memory deficit is rather common in women with eclampsia. Other deficits of higher cortical function can be observed occasionally, such as Balint syndrome, Anton syndrome, dyscalculia, confusion, or disorientation. These deficits are transient in nature and quickly disappear in tandem with improving toxemia.
Medical Care: Considering the significant morbidity and even deaths associated with the condition, aggressive treatment of eclampsia is warranted. Close observation of the blood pressure of pregnant women is very important. Admission to an intensive care unit is justified. Eclampsia also adversely affects the fetus; therefore, when possible, labor should be promptly induced. If fetal lung maturity is a question, expeditious administration of corticosteroid is warranted. If induction and rapid vaginal delivery is not possible, abdominal delivery should be considered. Prevention of any subsequent seizures is another goal. In the past, the choice of anticonvulsant was controversial; however, 2 large multicenter randomized trials have put an end to the controversy—magnesium sulfate is now the drug of choice.
- Magnesium sulfate (MgSO 4 ) is superior to phenytoin sodium and diazepam in controlling recurrent seizures and is associated with lower neonatal morbidity and mortality rates. Magnesium sulfate should be administered as soon as possible after diagnosis of preeclampsia is confirmed. It should be administered immediately after a seizure, if not administered before.
- Control of hypertension is very important. If administration of magnesium sulfate does not reduce the blood pressure adequately, other antihypertensive agents should be used. Some of the commonly used agents are nifedipine, hydralazine, and labetalol. Nifedipine has the advantage of ease of administration via the sublingual route; the other 2 agents can be administered intravenously.
Surgical Care: Evaluation for retained products of conception and their removal may be helpful in cases of postpartum eclampsia.
Consultations: Consulting an ophthalmologist is recommended for evaluation of papilledema or retinal pathology.
Diet: No specific dietary restriction or supplementation is needed for the treatment of eclampsia. With increasing gestational age, serum ionized and total magnesium levels decrease significantly; however, dietary supplementation of magnesium is not known to have any advantages. Several studies evaluating effects of exercise and diet, including aerobic exercise, protein restriction, protein supplementation, increasing or decreasing salt intake, magnesium supplementation, and zinc supplementation, have not produced any clear answers. Various trials of supplementation with fish oil or oil of evening primrose, which are rich sources of long chain fatty acids, have not shown preventative effects consistently. Early studies of dietary calcium supplementation suggest that it may be helpful in preventing toxemia in women who are at highest risk and in women with a low dietary intake of calcium.
Activity: Patients with eclampsia are usually monitored in an intensive care setting, so activity is limited. Once they recover from eclampsia, normal activity can be resumed, depending on whether abdominal delivery was performed.
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