Eclampsia is a severe complication of preeclampsia. It’s a rare but serious condition where high blood pressure results in seizures during pregnancy. Seizures are periods of disturbed brain activity that can cause episodes of staring, decreased alertness, and convulsions (violent shaking).
Eclampsia is a known complication of preeclampsia during pregnancy and is associated with morbidity and mortality of both the mother and fetus if not properly diagnosed. Preeclampsia and eclampsia are one of the four categories associated with hypertensive disorders of pregnancy.[rx] The other three categories include chronic hypertension, gestational hypertension, and preeclampsia superimposed on chronic hypertension. Preeclampsia, the precursor to eclampsia, has had an evolving definition over recent years. The definition for preeclampsia initially included proteinuria as a diagnostic requirement, but this is no longer the case as some patients had advanced disease before proteinuria detection. Preeclampsia is defined as new-onset of hypertension with a systolic blood pressure greater than or equal to 140 mmHg and/or diastolic blood pressure greater than or equal to 90 mmHg after 20 weeks of gestation with proteinuria and/or end-organ dysfunction (renal dysfunction, liver dysfunction, central nervous system disturbances, pulmonary edema, and thrombocytopenia).[rx][rx] Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia. Eclamptic seizures can occur antepartum, 20 weeks after gestation, intrapartum, and postpartum. Seizures before 20 weeks are rare but have been documented in gestational trophoblastic disease.[rx]
Pathophysiology
There are two proposed pathophysiologic mechanisms for eclampsia, both of which stem from the initial disease process, preeclampsia. The pathogenesis of preeclampsia is linked to abnormal placentation. In a normal pregnancy, fetal cytotrophoblasts migrate into the maternal uterus and cause remodeling of the endometrial vasculature for the blood supply of the placenta. In preeclampsia, there is an inadequate invasion of the cytotrophoblasts, thus leading to poor remodeling of the spiral arteries, which reduces the blood supply to the placenta. Abnormal blood supply leads to increased uterine arterial resistance and vasoconstriction, which ultimately produces placental ischemia and oxidative stress. Free radicals and cytokines, such as vascular endothelial growth factor 1 or VEGF, are released as a direct result of oxidative stress, which leads to endothelial damage. [rx] In addition, angiogenic or pro-inflammatory proteins negatively contribute to maternal endothelial function.[rx][rx] Endothelial disruption occurs not only at the site of the uterus but also at the cerebral endothelium, which leads to neurological disorders, including eclampsia.[rx] Another proposed mechanism is that elevated blood pressure from preeclampsia causes dysfunction of autoregulation of the cerebral vasculature, which causes hypoperfusion, endothelial damage, or edema.[rx]
Causes of Eclampsia
The exact etiology of eclampsia is still unclear despite the advances in the understanding of preeclampsia. It is proposed that there is increased permeability of the blood-brain barrier during preeclampsia, which causes an alteration to cerebral blood flow due to impaired autoregulation.[rx]
- chronic hypertension
- kidney disease
- diabetes mellitus
- autoimmune conditions, such as lupus (systemic lupus erythematosus or SLE)
- being pregnant for the first time
- body mass index (BMI) over 30
- family history of preeclampsia (mother or sister)
- being older than 35
Symptoms of Eclampsia
Eclampsia is a disorder of pregnancy characterized by seizures in the setting of pre-eclampsia.[rx] Typically the pregnant woman develops hypertension and proteinuria before the onset of a convulsion (seizure).[rx]
- Long-lasting (persistent) headaches
- Blurred vision
- Photophobia (i.e. bright light causes discomfort)
- Abdominal pain
- Either in the epigastric region (the center of the abdomen above the navel, or belly-button)
- And/or in the right upper quadrant of the abdomen (below the right side of the rib cage)
- Altered mental status (confusion)
- Protein in the urine
- Elevated blood pressure (>140 mmHg systolic or >90 mmHg diastolic)
- Abdominal pain
- Decreased urine output
- Signs of “fetal distress,” i.e. indications that the baby is having problems
- Low blood platelet count
Any of these symptoms may present before or after a seizure occurs.[rx] It is also possible that none of these symptoms will develop.
Other cerebral signs may immediately precede the convulsion, such as nausea, vomiting, headaches, and cortical blindness. If the complication of multi-organ failure ensues, signs and symptoms of those failing organs will appear, such as abdominal pain, jaundice, shortness of breath, and diminished urine output.
Onset
The seizures of eclampsia typically present during pregnancy and prior to delivery (the antepartum period)[rx], but may also occur during labor and delivery (the intrapartum period) or after the baby has been delivered (the postpartum period).[rx][rx][rx] If postpartum seizures develop, it is most likely to occur within the first 48 hours after delivery. However, late postpartum seizures of eclampsia may occur as late as 4 weeks after delivery.[rx][rx]
The following are common symptoms of preeclampsia:
- elevated blood pressure
- swelling in your face or hands
- headaches
- excessive weight gain
- nausea and vomiting
- vision problems, including episodes with loss of vision or blurry vision
- difficulty urinating
- abdominal pain, especially in the right upper abdomen
- seizures
- loss of consciousness
- agitation
Diagnosis of Eclampsia
History and Physical
Eclampsia is a disease process primarily related to the diagnosis of preeclampsia and can occur antepartum, during delivery, and up to 6 weeks post-partum. Women with eclampsia generally present after 20 weeks of gestation, with a majority of cases occurring after 28 weeks of gestation. The hallmark physical exam finding for eclampsia is generalized tonic-clonic seizures, which typically last 60 to 90 seconds in duration. A postictal state is often present after seizure activity. Patients can have warning symptoms such as a headache, visual changes, abdominal pain, and increased blood pressure before the onset of seizure activity.[rx][rx]
Evaluation
Patients with eclampsia present with generalized tonic-clonic seizures. The evaluation for eclampsia is centered around the diagnosis of preeclampsia as it is a known life-threatening complication of this disease process. The diagnosis of preeclampsia is primarily centered on blood pressure as the patient develops new-onset hypertension after 20 weeks of gestation. Patients with a systolic blood pressure of greater than or equal to 140 mmHg and/or diastolic blood pressure greater than or equal to 90 mmHg meet the criteria for new-onset hypertension. In addition to elevated blood pressure, patients also have one of the following: proteinuria, renal dysfunction, liver dysfunction, central nervous system symptoms, pulmonary edema, and thrombocytopenia.[rx] Proteinuria is no longer essential for the diagnosis of preeclampsia; however, this criterion is often still included in the current diagnosis. Proteinuria is defined as at least 300 mg of protein in a 24-hour urine sample or a urinary protein/creatinine ratio of 0.3 or greater.[rx] Other essential labs include a hepatic panel to assess liver function, a CBC to assess platelet function, and a basic metabolic profile to assess GFR and kidney function. Transaminase levels greater than two times the upper limit of normal with or without right upper quadrant or epigastric pain are consistent with preeclampsia. Platelet levels greater than 100,000 also are included in the diagnosis of preeclampsia. The presence of pulmonary edema on chest x-ray or exam in conjunction with elevated blood pressure is concerning for the development of preeclampsia. Central nervous symptoms associated with preeclampsia diagnosis include headache and visual disturbances.[rx]
Obstetric ultrasound imaging with Doppler ultrasonography is useful to assess the effects of preeclampsia on the fetus, such as intrauterine growth restriction. Ultrasound is also useful to monitor for further complications such as placental abruption. Fetal nonstress tests should be performed to assess the fetus antepartum.[rx]
Treatment of Eclampsia
Convulsions
Convulsions are prevented and treated using magnesium sulfate.[rx] The study demonstrating the effectiveness of magnesium sulfate for the management of eclampsia was first published in 1955.[rx] Serum magnesium concentrations associated with maternal toxicity as well as neonatal respiratory depression, low muscle tone, and low Apgar scores[48] are:
- 7.0–10.0 mEq/L: loss of patellar reflex
- 10.0–13.0 mEq/L: respiratory depression
- 15.0–25.0 mEq/L: altered atrioventricular conduction and (further) complete heart block
- >25.0 mEq/L: cardiac arrest
With intravenous administration the onset of anticonvulsant action is fast and lasts about 30 minutes. Following intramuscular administration the onset of action is about one hour and lasts for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.[rx]
Even with therapeutic serum magnesium concentrations, recurrent convulsions may occur, and additional magnesium may be needed, but with close monitoring for respiratory, cardiac, and neurological depression. If magnesium administration with resultant high serum concentrations fail to control convulsions, the addition of other intravenous anticonvulsants may be used, facilitate intubation and mechanical ventilation, and to avoid magnesium toxicity including maternal thoracic muscle paralysis.
Magnesium sulfate results in better outcomes than diazepam, phenytoin or a combination of chlorpromazine, promethazine, and pethidine.[rx][rx][rx]
Blood pressure management
Blood pressure control is used to prevent stroke, which accounts for 15 to 20 percent of deaths in women with eclampsia.[rx] The agents of choice for blood pressure control during eclampsia are hydralazine or labetalol.[rx] This is because of their effectiveness, lack of negative effects on the fetus, and mechanism of action. Blood pressure management is indicated with a diastolic blood pressure above 105–110 mm Hg.[rx]
Delivery
If the baby has not yet been delivered, steps need to be taken to stabilize the woman and deliver her speedily. This needs to be done even if the baby is immature, as the eclamptic condition is unsafe for both baby and mother. As eclampsia is a manifestation of a type of non-infectious multiorgan dysfunction or failure, other organs (liver, kidney, lungs, cardiovascular system, and coagulation system) need to be assessed in preparation for delivery (often a cesarean section), unless the woman is already in advanced labor. Regional anesthesia for cesarean section is contraindicated when a coagulopathy has developed.
There is limited to no evidence in favor of a particular delivery method for women with eclampsia. Therefore, the delivery method of choice is an individualized decision.[rx]
Monitoring
Invasive hemodynamic monitoring may be elected in an eclamptic woman at risk for or with heart disease, kidney disease, refractory hypertension, pulmonary edema, or poor urine output.[rx]
Eclamptic seizures are a medical emergency and require immediate treatment to prevent mortality in both the mother and fetus. Actively seizing patients should have their airway secured to prevent aspiration. The patient should be placed on her left side, and suction should be applied to help with oral secretions. Other airway adjuncts should also be readily available if the patient deteriorates and requires intubation. Magnesium sulfate should be given to control convulsions and is the first-line treatment for eclamptic seizures. A loading dose of 4 to 6 grams should be given intravenously over 15 to 20 minutes. A maintenance dose of 2 g per hour should subsequently be administered. Magnesium treatment should be continued for at least 24 hours after a patient’s last seizure.[rx][rx] Special attention must be made when giving this medication as it can lead to toxicity and cause respiratory paralysis, central nervous system depression, and cardiac arrest. It is essential to monitor reflexes, creatinine function, and urine output with magnesium administration.[rx] Other antiepileptic medications include diazepam or phenytoin. Benzodiazepines and barbiturates are used for refractory seizures that are unresponsive to magnesium.[rx] Levetiracetam or valproic acid are alternatives for myasthenic patients with eclampsia as magnesium and phenytoin cause increased muscle weakness, which could lead to a myasthenia crisis.[rx] Ultimately, immediate obstetrics consultation is required. Women with severe preeclampsia, who are greater than 34 weeks gestation and are unstable either from a maternal or fetal perspective, should undergo delivery as soon as the mother is stabilized.[rx] Corticosteroids should be given to women with fetal gestation less than 34 weeks if time and circumstances permit to help aide in lung maturation. Delivery should not be delayed for steroid administration. Ultimately, the definitive treatment for preeclampsia/eclampsia is delivery of the fetus. The route of delivery, as well as timing, is based on maternal and fetal factors.
Patients with severe preeclampsia should be given magnesium sulfate prophylactically to prevent eclamptic seizures. In addition, it is important to control blood pressure in pregnant women with preeclampsia. The American College of Obstetrics and Gynecology recommends that outpatient antihypertensive treatment should be started in women with systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 110 mmHg. First-line pharmacological treatment of hypertension in pregnant women includes labetalol, nifedipine, and hydralazine.[rx] The initial dose of labetalol is 20 mg IV. This dose can be doubled to 40 mg and then 80 mg at ten-minute intervals until target blood pressure is reached. IV hydralazine is dosed at 5 to 10 mg over two minutes. An additional 10 mg IV can be administered after twenty minutes if the systolic blood pressure is greater than 160 mmHg or the diastolic blood is greater than 110 mmHg. Nifedipine is given orally at an initial dose of 10 mg. If the systolic blood pressure is greater than 160 mmHg or diastolic greater than 110 after thirty minutes, then give an additional 20 mg of nifedipine. A second dose of 20 mg of nifedipine can be given after an additional 30 minutes.[rx]
Blood pressure control is also crucial postpartum as the risk for eclampsia is highest during the 48 hours after birth. Systolic blood pressure should be less than 150 mmHg, and diastolic pressure should be less than 100 mmHg on two readings at least four hours apart. Treatment should also be initiated if the systolic blood pressure is greater than 160 mmHg or diastolic blood pressure is greater than 110 mmHg after one hour. Magnesium sulfate should be continued for 12-24 hours post-delivery.[rx]
Differential Diagnosis
A list of differential diagnoses should be based on the patient’s history and physical exam findings. Differential diagnoses to consider include electrolyte abnormalities, toxins, infection, head trauma, ruptured aneurysm, and brain malignancy. If the patient is having persistent neurological symptoms, one should also consider stroke and intracranial hemorrhage.
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Chronic hypertension
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Chronic renal disease
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Primary seizure disorders
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Gallbladder disease
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Antiphospholipid syndrome
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Hemolytic-uremic syndrome.
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Pancreatic disease
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Immune thrombocytopenic purpura
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Thrombotic thrombocytopenic purpura
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Toxins
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Ruptured aneurysm
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Brain tumor
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Stroke
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Intracranial hemorrhage
References