Dr Soraya Saleh GargariFellowship feto- maternal medicine

from Royal College of EnglandShahid Beheshti university

Mahdyeh Hospital

Eclampsia

— Eclampsia is the occurrence of convulsions or coma unrelated to other cerebral conditions with signs and symptoms of preeclampsia

INCIDENCE AND EPIDEMIOLOGY — An eclamptic seizure occurs in 2 to 3 % of severely PIH women not receiving anti-seizure prophylaxis; the seizure rate is estimated to be between 0 and 0.6 % in women with “mild” PIH .

The incidence of eclampsia has been relatively stable at 1.6 to 10 cases per 10,000 deliveries in developed countries . In developing countries, however, the incidence varies widely: from 6 to 157 cases per 10,000 deliveries

Risk factors for eclampsia are similar to those for preeclampsia . 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: antepartum, intrapartum, postpartum — the timing and frequency of eclampsia is antepartum (38 to 55%), intrapartum (13 to 36 %), less than or equal to 48 hours postpartum (5 to 39 %), and greater than 48 hours postpartum (5 to 17 %))

Almost all cases (91%) of eclampsia develop in the third trimester (≥28 weeks) The remaining cases occur between 21 and 27 weeks’ gestation (7.5%) or at or before 20 weeks’ gestation (1.5%)

Late postpartum eclampsia is defined as eclampsia that occurs more than 48 hours but less than 4 weeks after delivery. Historically, eclampsia was believed not to occur more than 48 hours after delivery.

However, several recent reports have confirmed the existence of late postpartum eclampsia. These women have signs and symptoms consistent with preeclampsia in association with convulsions.

Some of these women demonstrate a clinical picture of preeclampsia during labor or immediately postpartum (56%), whereas others demonstrate these clinical findings for the first time more than 48 hours after delivery (44%).

Therefore, women in whom convulsions develop in association with hypertension or proteinuria or with headaches or blurred vision after 48 hours of delivery should be considered to have eclampsia and initially treated as such.

Cerebral Pathology Autoregulation of the cerebral circulation is a mechanism for the maintenance of constant cerebral blood flow during changes in BP and may be altered in eclampsia. Through active changes in cerebrovascular resistance at the arteriolar level, cerebral blood flow normally remains relatively constant when cerebral perfusion pressure ranges between 60 and 120 mm Hg.

PATHOGENESIS OF SEIZURES — The exact cause of seizures in women with eclampsia is not known. The following two hypotheses have been proposed :●Cerebral overregulation in response to high systemic blood pressure results in vasospasm of cerebral arteries, underperfusion of the brain, localized ischemia/infarction, and 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.

CLINICAL MANIFESTATIONS AND DIAGNOSISMaternal — 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 3 to 4 min (usual duration 60 to 75 seconds).

Symptoms that may occur in the hours before the seizure include persistent frontal or occipital headaches or thunderclap headaches, visual disturbances , right upper quadrant or epigastric pain, altered mental status, and shortness of breath. The relationship between the level of blood pressure elevation and onset of seizures is unclear.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

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 . If cerebral imaging is performed, MRI is the optimal study.

Fetal — Fetal bradycardia lasting at least 3 to 5 min 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 tachysystole.Resolution of maternal seizure activity is associated with compensatory fetal tachycardia and loss of variability, sometimes associated with transient FHR decelerations.

If the FHR tracing remains nonreassuring for more than 10 to 15 min with no improvement despite maternal and fetal resuscitative interventions, then the possibility of an occult abruption should be considered and emergent delivery may be indicated.

MANAGEMENT — 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

Maternal hypoxemia and acidosis may develop in women who have had repetitive convulsions, in those with aspiration pneumonia, in those with pulmonary edema, or as a result of a combination of these factors. It is the author’s policy to use transcutaneous pulse oximetry to monitor oxygenation in all eclamptic patients. Arterial blood gas analysis is required if the pulse oximetry results are abnormal (oxygen saturation ≤92%). Sodium bicarbonate is not given unless the pH is below 7.10.

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 deliveryThe 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 and maternal age . It is not clear whether there is a threshold pressure above which emergent therapy should be instituted in pregnant hypertensive women . Most experts recommend aggressive antihypertensive therapy for sustained diastolic pressures greater than 105 to 110 mmHg or systolic blood pressures ≥160 mmHg, although the validity of thresholds has not been tested prospectively.

Options for initial treatment of hypertensive crisis 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 an eclamptic 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. In women with extremely severe hypertension (≥180/120 mmHg), a diastolic goal of 100 to 105 mmHg should be achieved within two to six hours, with the maximum initial (within 10 to 20 minutes) fall in BP not exceeding 25 percent of the presenting value . An additional therapeutic option in these women is nicardipine beginning with 5 mg/hour intravenously and increased by 2.5 mg/hour every 5 to 15 minutes to a maximum dose of 15 mg/hour.

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 . 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

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 . 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 CNS, where it achieves anticonvulsant levels within 1 min, and will control seizures in greater than 80 % of patients within 5 min. 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. The duration of diazepam's acute anticonvulsant effect is typically less than 20 min.

Lorazepam 0.02 to 0.03 mg/kg intravenously, allowing approximately 1 min 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/min 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 2 min. The clinical advantage of lorazepam is that the effective duration of action against seizures is as long as 4 to 6 hours.

●Sodium amobarbital 250 mg intravenously over 3 to 5 min.

Delivery — The definitive treatment for eclampsia is prompt delivery; however, this does not necessarily preclude induction of labor and attempted vaginal delivery. Induction is a reasonable option for women with a favorable cervix at any gestational age or who are greater than 32 to 34 weeks of gestation.Cervical ripening agents can be used to improve the Bishop score; however, in our opinion, long inductions should be avoided and a clear endpoint for delivery planned (eg, within 24 hours).

Because the fetus benefits from in utero resuscitation before delivery, 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.

POSTPARTUM COURSE — Maternal vital signs, input, and output should be monitored closely to detect large changes in blood pressure and fluid imbalance AT LEAST 48 HOURS. Anticonvulsant drugs are generally administered for 24 to 48 hours postpartum, when the risk of recurrent seizures is low. 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).

 Maternal complications occur in up to 70 % of women with eclampsia and include :abruptio placentae (7% to 10%), DIC (7% to 11%), pulmonary edema (3% to 5%), acute renal failure (5% to 9%), aspiration pneumonia (2% to 3%), and cardiopulmonary arrest (2% to 5%).

Maternal Eclampsia is associated with a slightly increased risk for maternal death in developed countries (0% to 1.8%),but the maternal mortality rate may be as high as 14% in developing countries.

The high maternal mortality reported from developing countries occurs primarily among patients who have had multiple seizures outside the hospital and those without prenatal care. In addition, this high mortality rate could be attributed to the lack of resources and intensive care facilities needed to manage maternal complications from eclampsia.

Perinatal outcome — Premature delivery, abruptio placenta, and intrauterine asphyxia are the primary causes of perinatal death in eclamptic pregnancies. Perinatal mortality ranges from 2 to 23 percent and is closely related to gestational age.

Maternal Transport of the Eclamptic PatientDuring the past 20 years, there has been a marked reduction in the number of eclamptic patients. Consequently, most obstetricians have little or no experience in the management of eclampsia.

Because management of the eclamptic patient requires the availability of neonatal and obstetrical intensive care units and personnel with special expertise, it is recommended that eclamptic women at term be cared for only at level II or III hospitals with adequate facilities and with consultants from other specialties.

For those eclamptic patients who are remote from term, referral should be made to a tertiary care center.

The following steps should be taken before transfer of these critically ill patients:1. The referring physician or nurse should consult with the physician at the perinatal center regarding the referral and appropriate treatment. All maternal records, including prenatal data and a detailed summary of the patient’s condition, should be transmitted.2. BP should be stabilized and convulsions controlled.3. Adequate prophylactic anticonvulsive medications should be given. An accepted regimen is 4 g intravenous magnesium sulfate as a loading dose over 20 minutes

4. Maternal laboratory assessment (complete blood count with platelet count, liver enzymes) and fetal monitoring should be undertaken.

5- sent in an ambulance with medical personnel in attendance for proper management in case of subsequent convulsions

Recurrence risk — Recurrent eclampsia occurs in 2 percent of subsequent pregnancies . The risk appears to be reduced by close maternal monitoring and timely intervention if preeclampsia develops. Preeclampsia, however, cannot be prevented in most cases.

Subsequent pregnancies in women with a history of severe PIH or eclampsia are also at increased risk of other obstetric complications compared to women with no such history. These problems include :●Abruptio placenta (2.5 to 6.5 versus 0.4 to 1.3 percent of the general obstetrical population)●PTL (15 to 21 versus 12 percent)●IUGR (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 .

PREVENTIONCan eclampsia be predicted? — The relationship between hypertension, signs and symptoms of cortical irritability 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 . 20 to 38 % of eclamptic patients have a maximal blood pressure less than 140/90 prior to their seizure and about 20 % have no evidence of proteinuria

Many cases of eclampsia do not appear to be preventable, even among women receiving regular prenatal care, or those who are hospitalized..

Overall, the percentage of eclampsia considered unpreventable in these series ranges from 31% to 87%.86