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Reviews

A Current Concept of Eclampsia

HADASSAH LIPSTEIN, MD, CHRISTOPHER C. LEE, MD, AND ROBERT S. CRUPI, MD

Eclampsia is defined by the occurrence of seizures resulting from hy-pertensive encephalopathy on the background of preeclampsia. Thedevelopment of hypertension during pregnancy, a serious and poten-tially fatal condition, is a leading cause of maternal and fetal morbidityand death in the United States.1-3 It is a disease with preventable com-plications. The pathophysiology of hypertension during pregnancy isunclear, but there is consensus that aggressive treatment is warranted toprevent complications to both fetus and mother. A current concept ofpathophysiological character, diagnosis, prevention, and management

of eclampsia is discussed. (Am J Emerg Med 2003;21:223-226. 2003Elsevier Inc. All rights reserved.)

The following 5 types of hypertensive disorders cancomplicate pregnancy4-5: (1) gestational hypertension, alsocalled pregnancy-induced or transient hypertension; (2) pre-eclampsia; (3) eclampsia; (4) preeclampsia superimposedon chronic hypertension; and (5) chronic hypertension.

According to the protocol established by the WorkingGroup on High Blood Pressure in Pregnancy and the Amer-ican College of Obstetricians and Gynecology, a diagnosisof gestational hypertension is made when there is a sus-tained blood pressure 140/90 mm Hg, not associated with

proteinuria, that is diagnosed for the first time after 20weeks of pregnancy and returns to normal less than 12weeks postpartum.4,6,7 This diagnosis is further divided intomild to moderate and severe disease. There does not seem tobe an increased maternal or fetal risk with mild to moderatehypertension, which is a diastolic blood pressure (DBP)between 90 and 109 mm Hg.8 Although severe pregnancy-induced hypertension, defined as a systolic blood pressure(SBP) of170 or a DBP of110, is dangerous and mustbe treated, there is an even greater risk of perinatal andmaternal mortality and morbidity from preeclampsia andeclampsia.4 Sometimes called toxemia of pregnancy, theyare among the leading causes of maternal complications anddeath worldwide.9

Preeclampsia is characterized by hypertension diagnosedafter 20 weeks gestation plus proteinuria. In severe cases,

the DBP is 110 mm Hg, there is a persistent proteinuriaof 2 or more, and any of the following can be present:headaches, visual disturbances, upper abdominal pain, oli-guria, increased serum creatinine, thrombocytopenia, in-creased liver enzymes, fetal growth retardation, and pulmo-nary edema. A pregnant woman who presents with thesesymptoms must be treated immediately because this cansignify the imminent development of eclampsia.

Eclampsia is the new onset of seizures before, during, orafter labor, which is not attributable to other causes, in awoman with preeclampsia. Seizures in a pregnant womanwho had not been previously diagnosed with preeclampsiamust be accompanied by 2 of the following within 24 hoursof presentation to be considered eclamptic: hypertension,proteinuria, thrombocytopenia, or increased aspartate ami-notransferase.10 The onset of convulsions can be sudden inup to 16% of the cases.11 Among women with a previouslydiagnosed hypertensive disorder of pregnancy, those withsevere preeclampsia pose the highest risk of developing intoeclampsia.11

For years, investigators have attempted to gain a betterunderstanding of eclampsia, but still it remains a mystery.An exact etiology has not been discovered.7 It has beentheorized that eclampsia is the natural linear evolvementfrom preeclampsia. Eclampsia, however, has manifestedwithout warning or signs of preeclampsia. It has been re-ported that up to 38% of eclamptic seizures can occurwithout previous signs and symptoms.10 In a retrospectiveanalysis by Katz et al.,12 eclampsia was not found to be aprogression from preeclampsia. Questions as to the predict-ability of the seizures have been raised.8 Although currentpractice is to give prophylactic treatment to patients whopresent with preeclampsia, up to 40% of seizures occurbefore hospitalization.13 An additional 16% occur more than48 hours postpartum.13 Only half of all eclamptic seizures

can be expected to benefit form seizure prophylaxis.Because eclampsia remains a potentially life-threatening,

emergent condition of pregnancy, it would benefit all EDphysicians to possess a good understanding of the disease.In this review, we discuss the epidemiology, pathophysiol-ogy, signs and symptoms, complications, and preventionand management of eclampsia in an attempt to familiarizethe ED doctor with this dangerous but treatable condition.

EPIDEMIOLOGY

Seven percent to 15% of pregnancies are complicated byhypertensive disorders.6 Preeclampsia affects up to 7% ofpregnancies and1% of these women develop eclampsia.13

The incidence of eclampsia in the Western world is approx-

From the Department of Emergency Medicine, Flushing HospitalMedical Center, Flushing, NY.

Manuscript received and accepted July 24, 2002.Address reprint requests to Christopher C. Lee, MD, Department

of Emergency Medicine, Flushing Hospital Medical Center,45th Ave. at Parsons Blvd., Flushing, NY 11355. E-mail:Flushingerdoc@aol.com

Key Words: Eclampsia, pregnancy, hypertension, seizure. 2003 Elsevier Inc. All rights reserved.0735-6757/03/2103-0014$30.00/0

doi:10.1016/S0735-6757(02)42241-3

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imately 1 in 2,000 to 1 in 3,000 deliveries and can be higherin developing countries.14-17 In referral centers the ratereaches as high as 1 in 200 deliveries. Of the 500,000pregnancy-related deaths per annum, as many as 50,000result from eclampsia.7,18 Approximately 1 in 50 womenexperiencing eclamptic seizures will die annually fromcomplications.10 That figure can reach as high as 14% in the

nonindustrialized world.10

It has been reported that eclamp-sia results in stillbirths or neonatal demise at a rate of 1 in14.10 Although the incidence of preeclampsia has notchanged significantly over the past 6 decades, the rate ofmajor complications from the disease has been on a markeddecline.15

DEFINITIONS, SIGNS AND SYMPTOMS

Like previously mentioned, preeclampsia is defined as ablood pressure 140/90 mm Hg which is associated withproteinuria and pathologic edema. Proteinuria is character-ized by urine protein of 300 mg or more in a 24-hourcollection specimen or persistent 1 (30 mg/dL) urine

dipstick in random samples. The development of neurologicsymptoms, including: headache, visual disturbances, epi-gastric pain, oliguria, and depression of consciousness, area portent of incipient convulsions. Other signs that aid in thediagnosis of severe disease are thrombocytopenia, increasedliver enzymes, intrauterine growth restriction, and pulmo-nary edema.

Eclampsia is the new onset of seizures in a pregnantwoman that cannot be explained by any preexisting cerebralcondition. Lopez-Llera16 created a classification system ac-cording to the onset of the seizures. Antepartum eclampsiarefers to the onset of convulsions before the start of labor. Itis considered early if it occurs before 28 weeks gestation.

Convulsions that occur during labor are called intrapartumeclampsia, and postpartum eclampsia is the occurrence ofseizures within 7 days of delivery of the fetus and placenta.Intercurrent eclampsia, which is the least clinically signifi-cant of all but should not be ignored, refers to convulsionsthat appear antepartum but subside with enough clinicalimprovement to allow the continuation of the pregnancy forlonger than 1 week.

PATHOPHYSIOLOGY

A number of theories have been hypothesized as to theetiology of toxemia, including placental abnormalities, im-munologic disturbances, endothelial cell compromise, ge-

netic factors, and dietary influences.19 None of the investi-gations, as of yet, have resulted in concrete evidence, thusthe etiology remains unclear.7 There is a widespread beliefthat reduced uteroplacental perfusion is the central patho-physiological process involved in the development of pre-eclampsia.7 Odent,20 in his review, points out that an asso-ciation between preeclampsia and large-for-gestational-ageinfants, in addition to small-for-gestational-age infants,places doubt in that theory. He proposes that preeclampsiacould be the result of maternal-fetal conflict. EPA (a longchain n-3 polyunsaturated fatty acid) is required by thedeveloping fetal brain. The theory is that the fetus need forthe metabolites of EPA override the maternal need. A de-

crease in maternal EPA in preeclamptic and eclamptic

women as compared with their normotensive counterpartsappears to play a role in the development of this condition.Other studies tried to show a genetic basis for the disease. Afamily history of preeclampsia is associated with a fourfoldincreased risk of the disease in primigravidas.21 Chelsey etal. showed that daughters of mothers who had eclampsiawere at greater risk of developing the disease than daugh-

ters-in-law.7

Treloar et al.21

conducted studies to proveconcordance among monozygotic twin pairs. Their data didnot conclusively prove clear-cut maternal genetic influence;however, the existence of maternal genes that cause a sus-ceptibility to developing preeclampsia could not be ruledout.22 Decreased organ perfusion secondary to vasospasmand endothelial cell damage is also thought to play anetiologic role in the pathogenesis of the disease.4 Directobservation of vasospasm of the small blood vessels in nailbeds, ocular fundi, and bulbar conjunctivae supports thistheory. Histologic changes seen in blood vessel walls cor-roborate the concept of endothelial cell damage as an etio-logic factor. An investigation into the clinical parametersassociated with the development of brain edema of hyper-

tensive encephalopathy in toxemic patients conducted bySchwartz et al.23 showed an association between severedisease and abnormal red blood cell morphology and in-creased lactic dehydrogenase (LDH) levels. These findingsindicate the presence of microangiopathic hemolytic ane-mia, which suggests that endothelial damage does indeedplay a causative role in the pathogenesis of eclampsia.24-26

Other possible etiologic factors responsible for eclampticconvulsions include cerebral vasospasm, hemorrhage, oredema, metabolic, hypertensive encephalopathy.11

COMPLICATIONS

Women who develop preeclampsia or eclampsia are atincreased risk for a number of complications. Abruptioplacentae is the most common complication encountered,11

and there is a higher incidence among women with ante-partum eclampsia.17 A syndrome of hemolysis, elevatedliver enzymes, and a low platelet count, known as theHELLP syndrome, can complicate up to 10% of eclampticcases.11,27 Mortality resulting from the HELLP syndromeranges from 2% to 24% of cases.1 This too has a higherincidence in antepartum eclampsia.17 Other adverse prob-lems that can arise as a result of eclampsia include acuterenal failure, cerebrovascular and cardiovascular complica-tions, as well as maternal and fetal death.1 Cerebral hemor-rhage, the most serious complication, has been shown to be

the fatal event in 50% to 65% of the cases.1,11 Suddenincreases in severe diastolic blood pressure of120 mm Hgheighten the risk of death and developing lethal complica-tions such as hypertensive encephalopathy, ventricular ar-rhythmias, congestive heart failure, or disseminated intra-vascular coagulopathy.9 Pulmonary edema and aspirationpneumonia, which are usually iatrogenic, can develop as aresult of fluid overload and poor management.28 Munro10

reported a rate of 23% of women requiring ventilationresulting from eclampsia or its complications. Retinal de-tachment can also occur after an eclamptic seizure. Tran-sient neurologic deficits and transient cortical blindness,seen more often as a result of postpartum eclampsia,17 occur

in 3.1% and 2.3% of eclamptic women, respectively. Every

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effort must be taken to prevent the development of eclamp-sia to avoid these deadly repercussions.

PREVENTION AND MANAGEMENT

Because the etiology of eclampsia is not fully known, wemust view this disease from a different angle to prevent it

from occurring. Prima gravidity, lack of prenatal care, uri-nary tract infections, family history, diabetes mellitus, mul-tiple gestation, extremes of age, obesity, black ethnicity,preexisting hypertension, vascular renal disease, prolongedlabor, and hydatidiform moles can predispose a pregnantwoman to eclampsia.7,13 Awareness of these factors can aidin identifying those at greatest risk for developing thisdisease. Although it is a life-threatening condition, eclamp-sia can be prevented with proper antenatal care.29 Earlydetection is the key to successful management.3 Regularvisits throughout the pregnancy with an increase in thefrequency of visits in the third trimester has been shown tobe effective in limiting the morbidity and mortality fromeclampsia.1 Preventive therapy or early recognition and care

are associated with improved maternal and fetal outcomesas well.11 The best treatment for preeclampsia and eclamp-sia is delivery. If delivery is not possible or warranted, thenmanagement of the patient should include hospitalization,close observation, and prophylaxis against convulsions untiltermination can be performed. In-hospital care should in-clude daily evaluations with particular attention to clinicalfindings, daily weigh-ins, blood pressure readings every 4hours, and prophylactic anticonvulsive therapy.4 Prophylac-tic therapy for preeclampsia follows the same regimen astreatment for eclampsia. The accepted protocol in theUnited States, developed by Zuspan and modified by Sibaiand his colleagues, is a 6-g loading dose of magnesium

sulfate (MgSO4) administered intravenously followed by thecontinuous infusion of 2 g per hour.13 Special attention mustbe paid to the development of harmful side effects, such asoverdose which can lead to death, excessive bleeding, in-hibited spontaneous motility, increased blood loss, respira-tory depression, and pulmonary edema. Many trials havebeen done to determine the efficacy of the drug in prevent-ing and controlling eclamptic seizures. There is strong sup-port for the use of MgSO4 for seizure prophylaxis in severepreeclampsia.13,30 Limited evidence exists for the routineuse of MgSO4 for prophylaxis against convulsions in mildgestational hypertension and mild preeclampsia. The Col-laborative Eclampsia Trial Group proved the superiority ofMgSO4 for reducing recurrence of seizures.

14 In another

study, MgSO4 was shown to be superior to phenytoin anddiazepam for the prevention and treatment of eclampticconvulsions.7 Once eclampsia has occurred, medical man-agement with MgSO4 to stabilize the mother and preventfurther seizures is necessary. The therapy is continued for atleast 24 hours postpartum. Oxygen supplementation byfacemask is sufficient to treat hypoxia caused by the con-vulsions. If the airway is compromised, then intubation isrequired. High blood pressure should be managed with a5-mg loading dose of intravenous hydralazine, followedevery 20 minutes with 5 to 10 mg until a maximum of 80mg has been reached or the desired blood pressure has beenachieved. Once the mother is stabilized, the fetus condition

must be assessed. Fetal heart rate should be monitored and

a biophysical profile should be performed. Only after themother is stabilized can a delivery be attempted. The ulti-mate goal of the treating physician is the termination of thepregnancy with the least amount of trauma to the motherand baby, the birth of an infant who will eventually thrive,and complete restoration of maternal health.4 If a patient hashad a seizure and the diagnosis of eclampsia is made,

several anticonvulsant regimens can be used.The Eclampsia Trial Collaborative Group study included1,687 women with eclampsia who were randomly allocatedanticonvulsant regimens. The primary outcome measureswere recurrence of convulsions and maternal deaths. The453 women were randomized to magnesium sulfate com-pared with 452 given diazepam. Another 388 eclampticwomen were randomized to magnesium sulfate and com-pared with 387 women given phenytoin. The women allo-cated to magnesium sulfate therapy had a 50% reduction inincidence of recurrent seizures than those given diazepam(60 v 126 seizures, respectively). Maternal and perinatalmorbidity were not different between these 2 groups. In asecond comparison, the women randomized to receive mag-

nesium sulfate compared with phenytoin had a 67% reducedincidence of recurrent convulsions. Maternal mortality waslower in the magnesium group compared with the phenytoingroup (2.6% v 5.2%). The Collaborative Group concludedthat there is compelling evidence in favor of magnesiumsulfate rather than diazepam or phenytoin for the treatmentof eclampsia. If barbiturates are used, the choice is amobar-bital at a dose of 250 mg intravenously given over 3 to 5minutes.

DISCUSSION

Eclampsia is a potentially lethal but treatable hyperten-sive disorder of pregnancy. Review of current literaturesupports the use of MgSO4 for seizure prophylaxis in se-verely preeclamptic women. The benefit of prophylactictherapy for mild disease, however, is not clearly docu-mented. It has been reported that over the last few decadesthere has been a reduction in the incidence of eclampsia.15

Better management and regular antenatal care are partlyresponsible for this trend. Still, eclampsia is responsible foras many as 50,000 pregnancy-related deaths per year. Mostinvestigators have noted that the majority of maternal andfetal morbidity and mortality results from out-of-hospitalseizures.12 Currently, there are no reliable, valid, or eco-nomic methods of screening for eclampsia.4 Further studiesare required to gain additional knowledge and better under-

standing of the pathophysiology of this disease. In addition,investigations into uncovering reliable predictors of eclamp-sia are warranted so we can develop tests that will helpdetect eclampsia and prevent those seizures that are atpresent unpredictable. Until that time, familiarity withemergency management of toxemia of pregnancy and itscomplications is the best means of keeping the trend ofmorbidity and mortality from eclampsia on a downwardslope.

REFERENCES

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2. Witlin AG, Saade GR, Mattar F, Sibai BM: Risk factors forabruptio placentae and eclampsia: Analysis of 445 consecutivelymanaged women with severe preeclampsia and eclampsia. Am JObstet Gynecol 1999;180:1322-1329

3. Brady WJ, De Behnke DJ, Carter CT: Postpartum toxemia:Hypertension, edema, proteinuria and unresponsiveness in an un-known female. J Emerg Med 1995;13:643-648

4. Cunningham FG, Gant NF, Leveno KJ, et al: Williams obstet-rics. 21st ed. New York: McGraw Hill, 2001

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6. Lenfant C: National High Blood Pressure Education ProgramWorking Group report on high blood pressure in pregnancy. Am JObstet Gynecol 1990;163:1689

7. Ramin KD: The prevention and management of eclampsia.Obstet Gynecol Clin N Am 1999;26:489-503

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9. Repke JT, Robinson JN: The prevention and management ofpreeclampsia and eclampsia. Int J Gynaecol Obstet 1998;62:1-9

10. Munro PT: Management of eclampsia in the accident andemergency department. J Accid Emerg Med 2000;17:7-11

11. Usta IM, Sibai BM: Emergent management of puerperal

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13. Witlin AG, Sibai BM: Magnesium sulfate therapy in pre-eclampsia and eclampsia. Obstet Gyencol 1998;92:883-889

14. Duley L, et al: Which anticonvulsant for women with eclamp-sia? Evidence from the Colllaborative Eclampsia Trial. Lancet 1995;345:1455-1463

15. Leitch CR, Cameron AD, Walker JJ: The changing pattern ofeclampsia over a 60 year period. Brit J Obstet Gynaecol 1997;104:917-922

16. Lopez-Llera M: Main clinical subtypes of eclampsia. Am JObstet Gynecol 1992;166:4-9

17. Mattar F, Sibai BM. EclampsiaRisk factors for maternalmorbidity. Am J Obstet Gynecol 1999;182:307-312

18. Chien PFW, Khan KS, Arnott N: Magnesium sulphate in thetreatment of eclampsia and preeclampsia: An overview of the evi-dence from randomised trials. Brit J Obstet Gynaecol 1996;103:1085-1091

19. Maine D: Role of nutrition in the prevention of toxemia. Am JClin Nutr 2000;72:298S-300S

20. Odent M: Hypothesis: Preeclampsia as a maternal-fetal con-

flict. Med Gen Med J 2001;3:x-x21. Treolar SA, Cooper DW, Brennecke MB, et al: An Australian

twin study of the genetic basis of preeclampsia and eclampsia.Am J Obstet Gynecol 2001;184:374-381

22. Khatun S, Kanayama N, Belayet H, et al: Increased concen-trations of plasma neuropeptide Y in patients with eclampsia andpreeclampsia. Am J Obstet Gynecol 2000;182:896-900

23. Schwartz RB, Feske SK, Polak JF, et al: Preeclampsia-eclampsia: Clinical and neuroradiographic correlates ad insightsinto the pathogenesis of hypertensive encephalopathy. Radiology2000;217:371-376

24. Redman CW, Sergent IL: The pathogenesis of preeclampsia.Gynecol Obstet Fertil 2001;29:518-522

25. Sawhney H, Aggarwal N, Biswas R, et al: Maternal mortalityassociated with eclampsia and severe preeclampsia of pregnancy.J Obstet Gynaecol Res 2000;26:351-356

26. Sungani FC, Malata A, Masanjika R: Preeclampsia/eclamp-sia: A literature review. Cent Afr J Med 1998;44:261-26327. Haddad B, Barton JR, Livingston JC, Chahine R, Sibai BM:

Risk factors for adverse maternal outcomes among women withHELLP (hemolysis, elevated liver enzymes, and low platelet count)syndrome. Am J Obstet Gynecol 2000;183:444-448

28. Gilbert WM, Towner DR, Field NT, Anthony J: The safety andutility of pulmonary artery catheterization in severe preeclampsiaand eclampsia. Am J Obstet Gynecol 2000;182:1397-1403

29. Mahran M: Eclampsia: A leading cause of maternal mortality.J Perinat Med 2001;19:235-240

30. Hall DR, Odendaal HJ, Smith M: Is the prophylactic admin-istration of magnesium sulphate in women with preeclampsia indi-cated prior to labor. Brit J Obstet Gynaecol 2000;107:903-908

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