Preeclampsia that is complicated by generalized tonic–clonic convulsions is termed eclampsia. Once eclampsia has ensued, the risk to both mother and fetus is appreciable. Almost without exception, preeclampsia precedes the onset of eclamptic convulsions. Depending on whether convulsions appear before, during, or after labor, eclampsia is designated as antepartum, intrapartum, or postpartum. Eclampsia is most common in the last trimester and becomes increasingly more frequent as term approaches. The prognosis for eclampsia is always serious. Fortunately, maternal mortality due to eclampsia has decreased in the past three decades from 5 to 10 percent to less that 1 percent of cases.
Generally, eclampsia is more likely to be diagnosed too frequently rather than overlooked, because epilepsy, encephalitis, meningitis, cerebral tumor, cysticercosis, and ruptured cerebral aneurysm during late pregnancy and the puerperium may simulate eclampsia. Until other such causes are excluded, however, all pregnant women with convulsions should be considered to have eclampsia.
CLINICAL FEATURES OF ECLAMPSIA
Eclamptic seizures may be violent. During seizures, the woman must be protected, especially her airway. So forceful are the muscular movements that the woman may throw herself out of her bed, and if not protected, her tongue is bitten by the violent action of the jaws. This phase, in which the muscles alternately contract and relax, may last approximately a minute. Gradually, the muscular movements become smaller and less frequent, and finally the woman lies motionless. After a seizure, the woman is postictal, but in some, a coma of variable duration ensues. When the convulsions are infrequent, the woman usually recovers some degree of consciousness after each attack. As the woman arouses, a semiconscious combative state may ensue. In severe cases, coma persists from one convulsion to another, and death may result. In rare instances, a single convulsion may be followed by coma from which the woman may never emerge. However, as a rule, death does not occur until after frequent convulsions. Finally and also rarely, convulsions continue unabated—status epilepticus—and require deep sedation and even general anesthesia.
The duration of coma after a convulsion is variable. When the convulsions are infrequent, the woman usually recovers some degree of consciousness after each attack. As the woman arouses, a semiconscious combative state may ensue. In very severe cases, the coma persists from one convulsion to another, and death may result before she awakens. In rare instances, a single convulsion may be followed by coma from which the woman may never emerge, although, as a rule, death does not occur until after frequent convulsions.
Respirations after an eclamptic convulsion are usually increased in rate and may reach 50 or more per minute, in response presumably to hypercarbia from lactic acidemia, as well as to hypoxia. Cyanosis may be observed in severe cases. Fever of 39°C or more is a very grave sign, because it is probably the consequence of a central nervous system hemorrhage.
Proteinuria is almost always present and frequently pronounced. Urine output is likely diminished appreciably, and occasionally anuria develops. Hemoglobinuria is common, but hemoglobinemia is observed only rarely. Often, edema is pronounced—at times, massive—but it may also be absent.
As with severe preeclampsia, after delivery an increase in urinary output is usually an early sign of improvement. Proteinuria and edema ordinarily disappear within a week. In most cases, blood pressure returns to normal within a few days to 2 weeks after delivery. The longer hypertension persists postpartum, the more likely that it is the consequence of chronic vascular or renal disease.
In antepartum eclampsia, labor may begin spontaneously shortly after convulsions ensue and progress rapidly, sometimes before the attendants are aware that the unconscious or stuporous woman is having effective uterine contractions. If the convulsion occurs during labor, contractions may increase in frequency and intensity, and the duration of labor may be shortened. Because of maternal hypoxemia and lactic acidemia caused by convulsions, it is not unusual for fetal bradycardia to follow a seizure (Figure 24-1). This usually recovers within 3 to 5 minutes; if it persists more than about 10 minutes, another cause must be considered, such as placental abruption or imminent delivery.
FIGURE 24-1 Fetal bradycardia following an intrapartum eclamptic convulsion. Bradycardia resolved and beat-to-beat variability returned approximately 5 minutes following the seizure. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010.)
COMPLICATIONS OF ECLAMPSIA
Pulmonary edema following eclampsia usually develops postpartum and is most typically due to edema from increased pulmonary capillary permeability, cardiogenic edema or both. Administration of intravascular fluid in moderation and avoidance of volume expanding agents can limit this complication. Less commonly, aspiration of the gastric contents may occur with resulting lung injury.
In about 10 percent of women, some degree of blindness will follow an eclamptic seizure. There are at least two causes: (1) varying degrees of retinal detachment; and (2) occipital lobe ischemia, infarction, or edema. Whether due to cerebral or retinal pathology, the prognosis for return of normal vision is good and usually complete within a week.
Persistently Altered Neurologic State
About 5 percent of women will have substantively altered consciousness, including persistent coma, following a seizure. This is due to extensive cerebral edema, and transtentorial uncal herniation may cause death in such women.
In some women with eclampsia, sudden death occurs synchronously with a convulsion or follows shortly thereafter, as the result of a massive cerebral hemorrhage. Hemiplegia may result from sublethal hemorrhage. Cerebral hemorrhages are more likely in older women with underlying chronic hypertension. Rarely, they may be due to a ruptured berry aneurysm or arteriovenous malformation.
A standardized treatment has been continuously used to treat eclampsia at Parkland Hospital since 1955. The major components of this treatment regimen are shown in Table 24-1.
TABLE 24-1. Major Components of the Parkland Hospital Treatment Regimen for Eclampsia
Magnesium Sulfate to Control Convulsions
In more severe cases of preeclampsia, as well as eclampsia, magnesium sulfate administered parenterally is the effective anticonvulsant agent without producing central nervous system depression in either the mother or the infant. It may be given intravenously by continuous infusion or intramuscularly by intermittent injection (Table 24-2). The dosage schedule for severe preeclampsia is the same as for eclampsia. Because labor and delivery is a more likely time for convulsions to develop, women with preeclampsia–eclampsia usually are given magnesium sulfate during labor and for 24 hours postpartum. Magnesium sulfate is not given to treat hypertension.
TABLE 24-2. Magnesium Sulfate Dosage Schedule for Severe Preeclampsia and Eclampsia
Typically, the mother stops convulsing after the initial administration of magnesium sulfate, and within an hour or two regains consciousness sufficiently to be oriented as to place and time. About 10–15 percent of women receiving magnesium sulfate to arrest or prevent recurrent seizures will have a subsequent convulsion. An additional 2-g dose of magnesium sulfate in a 20-percent solution is administered slowly intravenously in such women. In a small woman, an additional 2-g dose may be used once and twice if needed in a larger woman. Sodium thiopental can be given slowly intravenously in women who are excessively agitated in the postconvulsion phase. Maintenance magnesium sulfate therapy for eclampsia is continued for 24 hours after delivery. For eclampsia that develops postpartum, magnesium sulfate is administered for 24 hours after the onset of convulsions.
Pharmacology and Toxicology of Magnesium Sulfate
Magnesium sulfate USP (US Pharmacopeial Convention) is MgSO4 · 7H2O and not MgSO4. Parenterally administered magnesium is cleared almost totally by renal excretion, and magnesium intoxication is avoided by ensuring that urine output is adequate, the patellar or biceps reflex is present, and there is no respiratory depression. Eclamptic convulsions are almost always prevented by plasma magnesium levels maintained at 4 to 7 mEq/L (4.8 to 8.4 mg/dL or 2.0 to 3.5 mmol/L). Patellar reflexes disappear when the plasma magnesium level reaches 10 mEq per L (approximately 12 mg/dL). When plasma levels rise above 10 mEq/L, respiratory depression develops, and at 12 mEq/L or more, respiratory paralysis and arrest follow. At high plasma levels, respiratory depression will develop that necessitates mechanical ventilation; depression of the sensorium is not dramatic as long as hypoxia is prevented. Treatment with calcium gluconate, 1 g intravenously, along with the withholding of magnesium sulfate usually reverses mild-to-moderate respiratory depression. Unfortunately, the effects of intravenously administered calcium may be short lived. For severe respiratory depression and arrest, prompt tracheal intubation and mechanical ventilation are lifesaving. Direct toxic effects on the myocardium from high levels of magnesium are uncommon. It appears that the cardiac dysfunction associated with magnesium is due to respiratory arrest and hypoxia. With appropriate ventilation, cardiac action is satisfactory even when plasma levels are exceedingly high.
Impaired Renal Function
Because magnesium is cleared almost exclusively by renal excretion, plasma magnesium concentration, using the doses described previously, will be excessive if glomerular filtration is decreased substantively. The initial standard dose of magnesium sulfate can be safely administered without knowledge of renal function. Renal function is thereafter estimated by measuring plasma creatinine, and whenever it is 1.3 mg/dL or higher, we give only half of the maintenance dose outlined in Table 24-2. With this renal impairment dosage, plasma magnesium levels are usually within the desired range of 4 to 7 mEq/L. Serum magnesium levels are used to adjust the infusion rate.
Magnesium ions in relatively high concentration will depress myometrial contractility both in vivo and in vitro. With the regimen described earlier and the plasma levels that have resulted, no evidence of myometrial depression has been observed beyond a transient decrease in activity during and immediately after the initial intravenous loading dose.
Magnesium administered parenterally to the mother promptly crosses the placenta to achieve equilibrium in fetal serum and less so in amnionic fluid. The neonate may be depressed only if there is severehypermagnesemia at delivery. We have not observed neonatal compromise after therapy with magnesium sulfate. Whether magnesium sulfate affects the fetal heart rate pattern, specifically beat-to-beat variability is controversial.
A variety of medications have been advocated for control of severe hypertension in women with eclampsia. Our first line of antihypertensive medications at Parkland Hospital is hydralazine.
At Parkland Hospital, hydralazine is given intravenously whenever the diastolic blood pressure is 110 mm Hg or higher, or the systolic pressure is 160 mm Hg or higher (see Table 24-1). Hydralazine is administered in 5- to 10-mg doses at 15- to 20-minute intervals until a satisfactory response is achieved. A satisfactory response antepartum or intrapartum is defined as a decrease in diastolic blood pressure to 90 to 100 mm Hg, but not lower lest placental perfusion be compromised. Hydralazine so administered has proven remarkably effective in the prevention of cerebral hemorrhage. Seldom is another antihypertensive agent needed because of poor response to hydralazine. The tendency to give a larger initial dose of hydralazine when the blood pressure is higher must be avoided. The response to even 5- to 10-mg doses cannot be predicted by the level of hypertension; thus, we always give 5 mg as the initial dose.
Intravenous labetalol is also used to treat acute hypertension. Labetalol lowers blood pressure more rapidly, and associated tachycardia is minimal. Our protocol calls for 10 mg intravenously initially. If the blood pressure has not decreased to the desirable level in 10 minutes, then 20 mg is given. The next 10-minute incremental dose is 40 mg followed by another 40 mg and then 80 mg if a salutary response is not yet achieved. We have found hydralazine to be more effective than labetalol.
Potent diuretics further compromise placental perfusion, because their immediate effects include intravascular volume depletion, which most often is already reduced due to eclampsia. Therefore, diuretics are not used to lower blood pressure lest they enhance the intensity of the maternal hemoconcentration and its adverse effects on the mother and the fetus.
Other Antihypertensive Agents
Although calcium-channel antagonists have been used with success, their use is much less common in obstetrical practice. Due to concerns about fetal cyanide toxicity, nitroprusside is not recommended unless there is no response to hydralazine, labetalol, or nifedipine.
Persistent Postpartum Hypertension
The potential problem of antihypertensive agents causing serious compromise of placental perfusion and fetal well being is obviated by delivery. If there is a problem after delivery in controlling severe hypertension and intravenous hydralazine or another agent that is being used repeatedly is effective in the puerperium, then other regimens can be used. We have had success with intramuscular hydralazine, usually in 10- to 25-mg doses at 4- to 6-hour intervals. Once repeated blood-pressure readings remain near normal, hydralazine is stopped.
If hypertension of appreciable intensity persists or recurs in these postpartum women, oral labetalol or a thiazide diuretic is given for as long as necessary. A variety of other antihypertensive agents have been utilized for this purpose, including other β-blockers and calcium-channel antagonists. The persistence or refractoriness of hypertension is likely due to at least two mechanisms: (1) underlying chronic hypertension, and (2) mobilization of edema fluid with redistribution into the intravenous compartment.
Intravenous Fluid Therapy
Lactated Ringer solution is administered routinely at the rate of 60 mL to no more than 125 mL per hour unless there was unusual fluid loss from vomiting, diarrhea, or diaphoresis, or more likely, excessive blood loss at delivery. Oliguria, common in cases of severe preeclampsia and eclampsia, coupled with the knowledge that maternal blood volume is very likely constricted compared with normal pregnancy, makes it tempting to administer intravenous fluids more vigorously. The rationale for controlled, conservative fluid administration is that the typical eclamptic woman already has excessive extracellular fluid that is inappropriately distributed between the intravascular and extravascular spaces. Infusion of large fluid volumes could and does enhance the maldistribution of extravascular fluid and thereby appreciably increases the risk of pulmonary and cerebral edema.
Invasive Hemodynamic Monitoring
The need for routine use of invasive hemodynamic monitoring for the woman with preeclampsia–eclampsia has not been established. Invasive monitoring should be considered for those women with multiple clinical factors such as intrinsic heart disease and/or advanced renal disease that might cause pulmonary edema. This is particularly relevant if pulmonary edema is inexplicable or refractory to treatment.
To avoid maternal risks from cesarean delivery, steps to effect vaginal delivery are employed initially in women with eclampsia. After an eclamptic seizure, labor often ensues spontaneously or can be induced successfully even in women remote from term. An immediate cure does not immediately follow delivery by any route, but serious morbidity is less common during the puerperium in women delivered vaginally.
Blood Loss at Delivery
Hemoconcentration, or lack of normal pregnancy-induced hypervolemia, is an almost predictable feature of severe preeclampsia–eclampsia. These women, who consequently lack normal pregnancy hypervolemia, are much less tolerant of blood loss than are normotensive pregnant women. It is of great importance to recognize that an appreciable fall in blood pressure very soon after delivery most often means excessive blood loss and not sudden dissolution of vasospasm. When oliguria follows delivery, the hematocrit should be evaluated frequently to help detect excessive blood loss that, if identified, should be treated appropriately by careful blood transfusion.
ANALGESIA AND ANESTHESIA
As regional analgesia techniques improved during the past decade, epidural analgesia has been promoted by some proponents as a therapy to ameliorate vaso-spasm and lower blood pressure. Moreover, many that favored epidural blockade believed that general anesthesia were inadvisable because stimulation caused by tracheal intubation may result in sudden maternal hypertension, which may cause pulmonary edema, cerebral edema, or intracranial hemorrhage. Others have also cited that tracheal intubation may be particularly hazardous in women with airway edema due to preeclampsia. These differing perspectives on the advantages, disadvantages, and safety of the anesthetic method used in the cesarean delivery of women with eclampsia have evolved so that most authorities now believe that epidural analgesia is the preferred method.
The immense popularity and increasing availability of epidural analgesia for labor has led many anesthesiologists as well as obstetricians to develop the viewpoint that epidural analgesia is an important factor in the intrapartum treatment of women with preeclampsia. Although epidural analgesia during labor is considered safe for women with pregnancy-associated hypertensive disorders, it has not been proven to be a therapy for hypertension.
For further reading in Williams Obstetrics, 22nd ed.,
see Chapter 34, “Pregnancy Hypertension.”