Eclampsia

DefinitionTop

Eclampsia is defined as the occurrence of a generalized seizure during pregnancy or the postpartum period usually in association with a diagnosis of preeclampsia. While eclampsia develops in 2% of individuals with severe preeclampsia, it is important to recognize that in >20% of cases prior hypertension may be absent. In at least a third of patients, eclampsia occurs for the first time post partum, usually within the first 5 days, but it can develop up to several weeks after. In these late cases, alternative etiologies are more likely.

TreatmentTop

1. Place the patient in a lateral decubitus position, ensure their airway is patent, and administer oxygen at a rate of 8 to 10 L/min. Ensure they are moved to a monitored setting such as a labor and delivery or an intensive care unit, where mental status, blood pressure, and oximetry can be continuously monitored.

2. Start anticonvulsant treatment: magnesium sulfateEvidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Magnesium sulfate has been found to more than halve the risk of eclampsia and, in women who have already had an eclamptic seizure, to be superior to phenytoin in reducing the risk of further seizures. Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD000025. doi: 10.1002/14651858.CD000025.pub2. Review. PMID: 21069663. Duley L, Henderson-Smart DJ, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD000128. doi: 10.1002/14651858.CD000128.pub2. Review. PMID: 20927719. 4 g IV over 20 minutes followed by 1 to 2 g/h in a continuous IV infusion for 24 hours after delivery or after the last seizure. Magnesium is cleared entirely through the kidney; therefore, if there is any evidence of renal impairment (creatinine >100 micromol/L or urine output <25 mL/h), the infusion rate of magnesium may need to be reduced to avoid toxicity, which can occur at levels >3.5 mmol/L (>3.5-5 mmol/L, loss of deep tendon reflexes; 5-6.5 mmol/L, respiratory paralysis; >7.5 mmol/L, cardiac conduction abnormalities). Magnesium levels should ideally be monitored in this situation to guide adjustment. If magnesium sulfate is ineffective (repeated seizures occur in ~10% of patients), our practice is to give one repeat bolus of magnesium 2 g IV before administering diazepam or midazolam 5 to 10 mg IV.

3. Maintain blood pressure at 140 to 160/90 to 110 mm Hg, for instance, using labetalol up to 20 to 40 mg IV every 20 minutes or as infusion if required (see Table 3 in Pregnancy-Related Hypertension). Use diuretics only if pulmonary edema is present. Oral agents can be used once the mother has recovered consciousness.

4. In the case of signs of fetal distress, urgent cesarean section may be necessary once the mother has been stabilized. However, the baby may also recover in utero as the maternal condition improves. In other cases, eclampsia is not an indication for cesarean section and vaginal delivery is possible (induced when necessary). The timing and mode of delivery is a decision for the obstetrician.

PreventionTop

The choice for both primary and secondary seizure prophylaxis in preeclampsia is magnesium sulfate.Evidence 2Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Magnesium sulfate has been found to more than halve the risk of eclampsia and, in women who have already had an eclamptic seizure, to be superior to phenytoin in reducing the risk of further seizures. Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD000025. doi: 10.1002/14651858.CD000025.pub2. Review. PMID: 21069663. Duley L, Henderson-Smart DJ, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD000128. doi: 10.1002/14651858.CD000128.pub2. Review. PMID: 20927719. It is thought to act as a neurostabilizer and cerebral vasodilator. In its use as primary prophylaxis, magnesium is given as a loading dose of 4 g IV over 20 to 40 minutes, then in a maintenance infusion of 1 g/h for 24 hours after delivery. Magnesium must be given in a monitored setting where adverse effects and urine output can be watched closely. Many obstetrical units have a protocol that includes frequent evaluation for signs of magnesium toxicity. These can include loss of deep tendon reflexes, double vision, respiratory depression, or signs of hypocalcemia. Magnesium levels are not usually monitored unless the serum creatinine level is increased or oliguria is present (see above).

Potential indications for primary magnesium sulfate prophylaxis include preeclampsia with any signs of neurologic involvement (vision change, irritability, severe headache, marked hyperreflexia and/or clonus); prophylaxis may also be given in patients with preeclampsia and severe features mandating urgent delivery. A decision to initiate magnesium as primary prophylaxis should always be undertaken in consultation with the treating obstetrician.

Follow-UpTop

Patients should be followed clinically for resolution of hypertension, proteinuria, and end-organ dysfunction. Hypertension and/or proteinuria persisting for >6 months post partum requires evaluation for causes unrelated to pregnancy.

Long-term cardiovascular risk: There is increasing recognition that preeclampsia is a risk factor for the development of both short-term and long-term cardiovascular events. Individuals with a history of a hypertensive disorder of pregnancy have increased risk of developing chronic hypertension, diabetes mellitus, early-onset coronary artery disease, and stroke, at a rate of roughly 2 to 4 times their baseline risk. The optimal timing and method of screening after the index pregnancy is still be determined. However, we recommend exercise (150 minutes per week of aerobic activity), aggressive cardiovascular risk factor modification, and regular screening for the development of risk factors (eg, blood pressure, glycated hemoglobin [HbA1c], lipid profile, body mass index [BMI]) in addition to the usual age-appropriate preventative screening.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. While hypertensive disorders of pregnancy are clearly associated with increased development of maternal cardiovascular risk factors and increased risk of cardiovascular events, evidence is still limited regarding the timing of development of risk factors, ideal methods of screening, and optimal clinical intervention. Heida KY, Bots ML, de Groot CJ, et al. Cardiovascular risk management after reproductive and pregnancy-related disorders: A Dutch multidisciplinary evidence-based guideline. Eur J Prev Cardiol. 2016 Nov;23(17):1863-1879. Epub 2016 Jul 18. Review. PMID: 27432836. Cain MA, Salemi JL, Tanner JP, Kirby RS, Salihu HM, Louis JM. Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes. Am J Obstet Gynecol. 2016 Oct;215(4):484.e1-484.e14. doi: 10.1016/j.ajog.2016.05.047. Epub 2016 Jun 2. PMID: 27263996. Cirillo PM, Cohn BA. Pregnancy complications and cardiovascular disease death: 50-year follow-up of the Child Health and Development Studies pregnancy cohort. Circulation. 2015 Sep 29;132(13):1234-42. doi: 10.1161/CIRCULATIONAHA.113.003901. Epub 2015 Sep 21. PMID: 26391409.

Recurrence risk: The risk of recurrence in a subsequent pregnancy is ~20%; however, the actual number is subject to some variation dependent on individual risk factors (see Preeclampsia). Acetylsalicylic acid (ASA) is thought to improve the development of placental vascularization around the time of placentation, thereby reducing the risk of subsequent early onset preeclampsia by up to 20% to 40%.

All individuals who have had a pregnancy complicated by preeclampsia should be advised to start receiving ASAEvidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (moderate confidence that we know true effects of the intervention). Of note, low-dose aspirin has not been demonstrated to increase the risk of placental abruption, postpartum hemorrhage, or fetal harm and may be associated with lower rates of preterm birth and intrauterine growth restriction. Henderson JT, Whitlock EP, O'Conner E, Senger CA, Thompson JH, Rowland MG. Low-Dose Aspirin for the Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Apr. Available from http://www.ncbi.nlm.nih.gov/books/NBK196392/ PubMed PMID: 24783270.Roberge S, Bujold E, Nicolaides KH. Meta-analysis on the effect of aspirin use for prevention of preeclampsia on placental abruption and antepartum hemorrhage. Am J Obstet Gynecol. 2018 May;218(5):483-489. doi: 10.1016/j.ajog.2017.12.238. Epub 2018 Jan 3. Review. PubMed PMID: 29305829. 81 to 162 mg daily (the dose is not entirely clear but likely >100 mg) during subsequent pregnancies initiated by 8 to 10 weeks’ and no later than 16 weeks’ gestation as well as supplemental calcium if their daily intake is <600 mg/d (target daily calcium of 1.2-2.5 g/d).Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. Calcium supplementation in doses >1 g/d has been found to be associated with a significant reduction in the risk of preeclampsia, particularly for women following low-calcium diets. While a review of 24 trials found good evidence to support the use of calcium supplementation as a safe and cheap way to reduce preeclampsia, its authors found that the treatment effect may be overestimated due to small-study effects or publication bias. Moreover, it is unclear how applicable these results are in women who achieve a normal dietary calcium intake. However, there is little evidence of harm.Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD001059. doi: 10.1002/14651858.CD001059.pub4. Review. PMID: 24960615.