Eclampsia

Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia.[1] Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protein in the urine or other organ dysfunction.[8][9] Onset may be before, during, or after delivery.[1] Most often it is during the second half of pregnancy.[1] The seizures are of the tonic–clonic type and typically last about a minute.[1] Following the seizure there is typically either a period of confusion or coma.[1] Complications include aspiration pneumonia, cerebral hemorrhage, kidney failure, pulmonary oedema, HELLP syndrome, coagulopathy, abruptio placentae and cardiac arrest.[1][10] Pre-eclampsia and eclampsia are part of a larger group of conditions known as hypertensive disorders of pregnancy.[1]

Eclampsia
SpecialtyObstetrics
SymptomsSeizures, high blood pressure[1]
ComplicationsAspiration pneumonia, cerebral hemorrhage, kidney failure, cardiac arrest[1]
Usual onsetAfter 20 weeks of pregnancy[1]
Risk factorsPre-eclampsia[1]
PreventionAspirin, calcium supplementation, treatment of prior hypertension[2][3]
TreatmentMagnesium sulfate, hydralazine, emergency delivery[1][4]
Prognosis1% risk of death[1]
Frequency1.4% of deliveries[5][6]
Deaths46,900 hypertensive diseases of pregnancy (2015)[7]

Recommendations for prevention include aspirin in those at high risk, calcium supplementation in areas with low intake, and treatment of prior hypertension with medications.[2][3] Exercise during pregnancy may also be useful.[1] The use of intravenous or intramuscular magnesium sulfate improves outcomes in those with eclampsia and is generally safe.[4][11] This is true in both the developed and developing world.[4] Breathing may need to be supported.[1] Other treatments may include blood pressure medications such as hydralazine and emergency delivery of the baby either vaginally or by cesarean section.[1]

Pre-eclampsia is estimated to affect about 5% of deliveries while eclampsia affects about 1.4% of deliveries.[5] In the developed world rates are about 1 in 2,000 deliveries due to improved medical care.[1] Hypertensive disorders of pregnancy are one of the most common causes of death in pregnancy.[12][13] They resulted in 46,900 deaths in 2015.[7] Around one percent of women with eclampsia die.[1] The word eclampsia is from the Greek term for lightning.[14] The first known description of the condition was by Hippocrates in the 5th century BC.[14]

Signs and symptoms
Diagram of the regions (or quadrants) of the abdomen, to assist in locating the right upper quadrant or the epigastric region, where eclampsia-associated pain may occur

Eclampsia is a disorder of pregnancy characterized by seizures in the setting of pre-eclampsia.[15] Pre-eclampsia is diagnosed when repeated blood pressure measurements are greater or equal to 140/90mmHg, in addition to any signs of organ dysfunction, including: proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, cerebral symptoms, or abdominal pain.[16]

Typically the pregnant woman develops hypertension and proteinuria before the onset of a convulsion (seizure).[17]

  • 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)

Any of these symptoms may present before or after a seizure occurs.[18] 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),[19] but may also occur during labor and delivery (the intrapartum period) or after the baby has been delivered (the postpartum period).[15][18][20] 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.[15][18]

Complications

There are risks to both the mother and the fetus when eclampsia occurs. The fetus may grow more slowly than normal within the womb (uterus) of a woman with eclampsia, which is termed intrauterine growth restriction and may result in the child appearing small for gestational age or being born with low birth weight.[21] Eclampsia may cause problems with the placenta to occur. The placenta may bleed (hemorrhage) or it may begin to separate from the wall of the uterus.[22][23] It is normal for the placenta to separate from the uterine wall during delivery, but it is abnormal for it to separate prior to delivery; this condition is called placental abruption and can be dangerous for the fetus.[24] Placental insufficiency may also occur, a state in which the placenta fails to support appropriate fetal development because it cannot deliver the necessary amount of oxygen or nutrients to the fetus.[22] During an eclamptic seizure, the beating of the fetal heart may become slower than normal (bradycardia).[21][25] If any of these complications occurs, fetal distress may develop. Treatment of the mother's seizures may also manage fetal bradycardia.[26][27] If the risk to the health of the fetus or the mother is high, the definitive treatment for eclampsia is delivery of the baby. Delivery by cesarean section may be deemed necessary, especially if the instance of fetal bradycardia does not resolve after 10 to 15 minutes of resuscitative interventions.[26][28] It may be safer to deliver the infant preterm than to wait for the full 40 weeks of fetal development to finish, and as a result prematurity is also a potential complication of eclampsia.[22][29]

In the mother, changes in vision may occur as a result of eclampsia, and these changes may include blurry vision, one-sided blindness (either temporary due to amaurosis fugax or potentially permanent due to retinal detachment), or cortical blindness, which affects the vision from both eyes.[30][31] There are also potential complications in the lungs. The woman may have fluid slowly collecting in the lungs in a process known as pulmonary edema.[22] During an eclamptic seizure, it is possible for a person to vomit the contents of the stomach and to inhale some of this material in a process known as aspiration.[21] If aspiration occurs, the woman may experience difficulty breathing immediately or could develop an infection in the lungs later, called aspiration pneumonia.[18][32] It is also possible that during a seizure breathing will stop temporarily or become inefficient, and the amount of oxygen reaching the woman's body and brain will be decreased (in a state known as hypoxia).[18][33] If it becomes difficult for the woman to breathe, she may need to have her breathing temporarily supported by an assistive device in a process called mechanical ventilation. In some severe eclampsia cases, the mother may become weak and sluggish (lethargy) or even comatose.[31] These may be signs that the brain is swelling (cerebral edema) or bleeding (intracerebral hemorrhage).[22][31]

Risk factors

Eclampsia, like pre-eclampsia, tends to occur more commonly in first pregnancies.[34][35][36] Women who have long term high blood pressure before becoming pregnant have a greater risk of pre-eclampsia.[34][35] Furthermore, women with other pre-existing vascular diseases (diabetes or nephropathy) or thrombophilic diseases such as the antiphospholipid syndrome are at higher risk to develop pre-eclampsia and eclampsia.[34][35] Having a large placenta (multiple gestation, hydatidiform mole) also predisposes women to eclampsia.[34][35][37] In addition, there is a genetic component: a woman whose mother or sister had the condition is at higher risk than otherwise.[38] Women who have experienced eclampsia are at increased risk for pre-eclampsia/eclampsia in a later pregnancy.[35] People of certain ethnic backgrounds can have an increased risk of developing pre-eclampsia and eclampsia. The occurrence of pre-eclampsia was 5% in white, 9% in Hispanic, and 11% in African American women. Black women were also shown to have a disproportionately higher risk of dying from eclampsia.[39]

Mechanism
Diagram of the placenta and its position in the uterus during pregnancy
Image of a placenta after delivery

The presence of a placenta is required, and eclampsia resolves if it is removed.[40] Reduced blood flow to the placenta (placental hypoperfusion) is a key feature of the process. It is accompanied by increased sensitivity of the maternal vasculature to agents which cause constriction of the small arteries, leading to reduced blood flow to multiple organs. Vascular dysfunction-associated maternal conditions such as Lupus, hypertension, and renal disease, or obstetric conditions that increase placental volume without an increase in placental blood flow (such as twin pregnancy) can increase risk for pre-eclampsia.[41] Also, an activation of the coagulation cascade may lead to microthrombi formation, which can further impair blood flow. Thirdly, increased vascular permeability results in the shift of extracellular fluid from the blood to the interstitial space, with further reduction in blood flow, and edema. These events lead to hypertension; renal, pulmonary, and hepatic dysfunction; and cerebral edema with cerebral dysfunction and convulsions.[40] Before symptoms appear, increased platelet and endothelial activation may be detected.[40]

Placental hypoperfusion is linked to abnormal modelling of the fetal–maternal placental interface that may be immunologically mediated.[40] Pre-eclampsia’s pathogenesis is poorly understood, but it likely is attributed to factors related to the mother and placenta, because pre-eclampsia is seen in molar pregnancies absent of a fetus or fetal tissue.[41] The placenta produces the potent vasodilator adrenomedullin: it is reduced in pre-eclampsia and eclampsia.[42] Other vasodilators are also reduced, including prostacyclin, thromboxane A2, nitric oxide, and endothelins, also leading to vasoconstriction.[25]

Eclampsia is a form of hypertensive encephalopathy: cerebral vascular resistance is reduced, leading to increased blood flow to the brain, cerebral edema and resultant convulsions.[43] An eclamptic convulsion usually does not cause chronic brain damage unless intracranial haemorrhage occurs.[44]

Diagnosis

If a pregnant woman has already been diagnosed with pre-eclampsia during the current pregnancy and then develops a seizure, she may be assigned a 'clinical diagnosis' of eclampsia without further workup. While seizures are most common in the third trimester, they may occur any time from 20 weeks of pregnancy until 6 weeks after birth.[45] A diagnosis of eclampsia is most likely given the symptoms and medical history, and eclampsia can be assumed to be the correct diagnosis until proven otherwise.[46] However, if a woman has a seizure and it is unknown whether or not she has pre-eclampsia, testing can help make the diagnosis clear.

Vital signs

One of the core features of pre-eclampsia is high blood pressure. Blood pressure is a measurement of two numbers. If either the top number (systolic blood pressure) is greater than 140 mmHg or the bottom number (diastolic blood pressure) is greater than 90 mmHg, then the blood pressure is higher than the normal range and the person has high blood pressure. If the systolic blood pressure is greater than 160 or the diastolic pressure is greater than 110, the hypertension is considered to be severe.[15]

Laboratory testing

Another core feature of pre-eclampsia is proteinuria, which is the presence of excess protein in the urine. To determine if proteinuria is present, the urine can be collected and tested for protein; if there is 0.3 grams of protein or more in the urine of a pregnant woman collected over 24 hours, this is one of the diagnostic criteria for pre-eclampsia and raises the suspicion that a seizure is due to eclampsia.[15]

In cases of severe eclampsia or pre-eclampsia, the level of platelets in the blood can be low in a condition termed thrombocytopenia.[47][25] A complete blood count, or CBC, is a test of the blood that can be performed to check platelet levels.

Other investigations include: kidney function test, liver function tests (LFT), coagulation screen, 24-hour urine creatinine, and fetal/placental ultrasound.

Differential diagnosis

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

Prevention

Detection and management of pre-eclampsia is critical to reduce the risk of eclampsia. The USPSTF recommends regular checking of blood pressure through pregnancy in order to detect preeclampsia.[48] Appropriate management of women with pre-eclampsia generally involves the use of magnesium sulfate to prevent eclamptic seizures.[49] In some cases, low-dose aspirin has been shown to decrease the risk of pre-eclampsia in pregnant women, especially when taken in the late first trimester.[16]

Treatment

The four goals of the treatment of eclampsia are to stop and prevent further convulsions, to control the elevated blood pressure, to deliver the baby as promptly as possible, and to monitor closely for the onset of multi-organ failure.

Convulsions

Convulsions are prevented and treated using magnesium sulfate.[50] The study demonstrating the effectiveness of magnesium sulfate for the management of eclampsia was first published in 1955.[51] Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. [52]

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. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration. [52] Magnesium sulfate is associated with several minor side effects; serious side effects are uncommon, occurring at elevated magnesium serum concentrations > 7.0 mEQ/L.  Serious toxicity can be counteracted with calcium gluconate. [53]

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.[54][55][56]

Blood pressure management

Blood pressure control is used to prevent stroke, which accounts for 15 to 20 percent of deaths in women with eclampsia.[57] The agents of choice for blood pressure control during eclampsia are hydralazine or labetalol.[25] 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.[28]

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 a delivery (often a caesarean section), unless the woman is already in advanced labor. Regional anesthesia for caesarean 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.[27]

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.[25]

Etymology

The Greek noun ἐκλαμψία, eklampsía, denotes a "light burst"; metaphorically, in this context, "sudden occurrence." The New Latin term first appeared in Johannes Varandaeus’ 1620 treatise on gynaecology Tractatus de affectibus Renum et Vesicae.[58] The term toxemia of pregnancy is no longer recommended: placental toxins are not the cause of eclampsia occurrences, as previously believed.[59]

In Downton Abbey, a historical drama television series, the character Lady Sybil dies (in series 3, episode 5) of eclampsia shortly after child birth.[60]

In Call the Midwife, a medical drama television series set in London in the 1950s and 1960s, the character (in series 1, episode 4) named Margaret Jones is struck with pre-eclampsia, ultimately proceeding from a comatose condition to death. The term "toxemia" was also used for the condition, in the dialogue.[61]

In House M.D., a medical drama television series set in the U.S., Dr. Cuddy, the hospital director, adopts a baby whose teenage mother dies from eclampsia and had no other parental figures available.[61]

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