acute complications of preeclampsia - ubc critical care medicine

Acute Complicationsof PreeclampsiaERROL R. NORWITZ, MD, PhD,* CHAUR-DONG HSU, MD,MPH,† and JOHN T. REPKE, MD†Departments of Obstetrics & Gynecology, *Brigham & Women’sHospital, Harvard Medical School, Boston, Massachusetts, and†University of Nebraska Medical Center, University of NebraskaMedical School, Omaha, Nebraska

Preeclampsia is an idiopathic multisystemdisorder specific to human pregnancy andthe puerperium.1 More precisely, it is a dis-ease of the placenta, because it has also beendescribed in pregnancies where there is tro-phoblast but no fetal tissue (complete molarpregnancies). Although the pathophysiol-ogy of preeclampsia is poorly understood, itis clear that the blueprint for its developmentis laid down early in pregnancy. It has beensuggested that the pathologic hallmark is acomplete or partial failure of the secondwave of trophoblast invasion from 16 to 20weeks’ gestation, which is responsible innormal pregnancies for destruction of themuscularis layer of the spiral arterioles.2 Aspregnancy progresses, the metabolic de-mands of the fetoplacental unit increase.However, because of the abnormally shal-low invasion of the placenta, the spiral arte-rioles are unable to dilate to accommodatethe required increase in blood flow, result-ing in “placental dysfunction” that manifests

clinically as preeclampsia. Although attrac-tive, this hypothesis remains to be validated.

Preeclampsia is a clinical diagnosis. Theclassic definition of preeclampsia encom-passes three elements: new-onset hyperten-sion (defined as a sustained sitting bloodpressure !140/90 mm Hg in a previouslynormotensive woman); new-onset protein-uria (defined as >300 mg/24 hours or !2+on a clean-catch urinalysis in the absence ofurinary tract infection); and new-onset sig-nificant nondependent edema.1 However,more recent consensus reports have sug-gested eliminating edema as a criterion forthe diagnosis.3

A more extensive synopsis of preeclamp-sia is beyond the scope of this discussion.This monograph serves to review in detailthe diagnosis and management of severalacute maternal complications of preeclamp-sia: eclampsia, HELLP (hemolysis, elevatedliver enzymes, low platelets) syndrome,liver rupture, pulmonary edema, renal fail-ure, disseminated intravascular coagulopa-thy (DIC), hypertensive emergency, and hy-pertensive encephalopathy and corticalblindness.

Correspondence: Errol R. Norwitz, MD, PhD, Depart-ment of Obstetrics & Gynecology, Brigham & Women’sHospital, Harvard Medical School, 75 Francis Street,Boston, MA 02115. E-mail: [email protected]

PROD. # GRF20214

CLINICAL OBSTETRICS AND GYNECOLOGYVolume 45, Number 2, 308–329© 2002, Lippincott Williams & Wilkins, Inc.

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 45 / NUMBER 2 / JUNE 2002

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EclampsiaEclampsia refers to the occurrence of one ormore generalized convulsions and/or comain the setting of preeclampsia and in the ab-sence of other neurologic conditions.1 Inthe past, eclampsia was thought to be theend result of preeclampsia, hence the no-menclature. However, it is now clear thatseizures are only one of several clinicalmanifestation of “severe” preeclampsia.The precise cause of seizures in womenwith eclampsia is not known. Proposed eti-ologies include cerebral vasospasm withlocal ischemia, hypertensive encephalopa-thy with hyperperfusion, vasogenic edema,and endothelial damage.4 Despite recentadvances in detection and management,preeclampsia/eclampsia remains the secondmost common cause of maternal death in theUnited States (after thromboembolic dis-ease), accounting for 15% of all maternaldeaths.5 It is estimated that eclampsia ac-counts for 50,000 maternal deaths per yearworldwide.6

EPIDEMIOLOGY AND INCIDENCEEclampsia is most common in nonwhite,nulliparous women from lower socioeco-nomic backgrounds. Peak incidence is in theteenage years and early 20s, but there is alsoan increased prevalence in women olderthan 35. Eclampsia before 20 weeks’ gesta-tion is rare; this should raise the possibilityof an underlying molar pregnancy or anti-phospholipid antibody syndrome.

The overall incidence of eclampsia isrelatively stable, at 4 to 5 cases per 10,000live births in developed countries.7 In devel-oping countries, however, the incidence var-ies widely from 6 to 100 per 10,000 livebirths.8

CLINICAL MANIFESTATIONS ANDDIAGNOSISEclampsia is a clinical diagnosis based onevidence of one or more generalized convul-sions and/or coma in a preeclamptic womanand in the absence of other neurologic con-

ditions. Eclamptic seizures are almost al-ways self-limiting and seldom last longerthan 3 to 4 minutes. Eclamptic seizures areclinically and electroencephalographicallyindistinguishable from other generalizedtonic-clonic seizures. In general, womenwith typical eclamptic seizures who do nothave focal neurologic deficits or prolongedcoma do not require either electroencepha-lographic or cerebral imaging studies.9

Clinical conditions other than eclampsia thatshould be considered when evaluating apregnant woman who has had a seizure arelisted in Table 1.

Approximately half of all cases ofeclampsia occur before term, with more than20% occurring before 31 weeks’ gestation.7

Three quarters of the remaining cases occurat term, developing intrapartum or within 48hours of delivery. Seizures due to eclampsiaalways resolve postpartum, often within afew hours to days. Diuresis (>4 L/day) is be-lieved to be the most accurate clinical indi-cator of resolution of preeclampsia/eclampsia,but it is not a guarantee against the develop-ment of seizures.10 Indeed, late postpartumeclampsia (eclamptic seizures developing>48 hours postpartum but <4 weeks postpar-

TABLE 1. Differential Diagnosis ofEclampsia

Cerebrovascular accidentIntracerebral hemorrhageCerebral arterial or venous thrombosis

Hypertensive diseasesHypertensive encephalopathyPheochromocytoma

Space-occupying lesions of the central nervoussystem

Brain tumorAbscess

Metabolic disordersHypoglycemiaUremiaInappropriate antidiuretic hormone secretion

resulting in water intoxicationInfectious etiology

MeningitisEncephalitis

Thrombotic thrombocytopenic purpuraIdiopathic epilepsy

Acute Complications of Preeclampsia 309

tum) accounts for 25% of postpartum casesand up to 16% of all cases of eclampsia.10,11

MANAGEMENTA number of management strategies havebeen developed to prevent maternal and fe-tal complications resulting from eclampsiaduring the peripartum period. The immedi-ate issues in caring for an eclamptic womaninclude maintenance of maternal vital func-tions, control of convulsions and blood pres-sure, prevention of recurrent seizures, andevaluation for delivery. If the seizure is wit-nessed, maintenance of airway patency andprevention of aspiration should be the firstresponsibilities of management. The partu-rient should be rolled onto her left side and apadded tongue blade placed in her mouth, ifpossible.

Control of ConvulsionsAlthough eclamptic seizures usually resolvewithout treatment within 3 to 4 minutes, ananticonvulsant can be administered toachieve resolution of an ongoing convul-sion. The treatment of choice is magnesiumsulfate. In women already receiving magne-sium seizure prophylaxis, a serum magne-sium level should be obtained immediatelyand a rapid intravenous infusion of 1 to 2 gadministered while awaiting the results. Inwomen not receiving seizure prophylaxis,magnesium should be given as a rapid intra-venous infusion of 2 g repeated every 15minutes to a maximum of 6 g. This loadingdose may be given safely even in the pres-ence of renal insufficiency. Exactly howmagnesium acts as an anticonvulsant ineclampsia is not known. Several mecha-nisms have been proposed, including selec-tive vasodilatation of the cerebral vascula-ture, protection of endothelial cells fromdamage by free radicals, prevention of cal-cium ion entry into ischemic cells, and/or asa competitive antagonist to the glutamate N-methyl-D-aspartate receptor (which is epi-leptogenic).12 Benzodiazepines have beenused in the past for eclamptic seizures. Di-azepam rapidly enters the central nervous

system, where it achieves anticonvulsantlevels within 1 minute, and it will controlseizures in greater than 80% of patientswithin 5 minutes.13 However, most investi-gators recommend avoiding benzodiaz-epines because of the potentially profounddepressant effects on the fetus. This effectbecomes clinically significant when the totalmaternal dose of diazepam exceeds 30 mg.

Treatment of HypertensionCerebrovascular accident accounts for 15–20% of deaths from eclampsia. The risk ofhemorrhagic stroke correlates directly withthe degree of elevation in systolic bloodpressure and is less related to, but not inde-pendent of, the diastolic pressure.14 It is notclear whether there is a threshold pressureabove which emergent therapy should be in-stituted.14 Most investigators recommendaggressive antihypertensive therapy for sus-tained diastolic pressures of more than 105to 110 mm Hg and systolic blood pressuresof 160 mmHg or greater,3 although thesethresholds have not been tested prospec-tively. The cerebral vasculature of womenwith underlying chronic hypertension canprobably tolerate higher systolic pressureswithout injury, whereas adolescents withnormally low blood pressures may benefitfrom starting treatment at lower levels. Per-sistent, severe elevation in blood pressure(!160/110 mm Hg) should be treated to pre-vent cerebrovascular accident. Initial treat-ment options include hydralazine (5 mg in-travenous push followed by 5- to 10-mg bo-luses as needed q 20 minutes) or labetalol(10–20 mg intravenous push, repeat q 10–20minutes with doubling doses not to exceed80 mg in any single dose, for a maximumtotal cumulative dose of 300 mg). Womenwho do not improve rapidly after control ofseizures and hypertension or those who de-velop localizing neurologic signs should beevaluated further.

Prevention of Subsequent SeizuresApproximately 10% of eclamptic womenwill have repeated seizures if managed ex-

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pectantly.15 There is universal agreementthat women with eclampsia require anticon-vulsant therapy to prevent further seizuresand the possible complications of repeatedseizure activity: neuronal death, rhabdomy-olysis, metabolic acidosis, aspiration pneu-monitis, neurogenic pulmonary edema, andrespiratory failure. However, the choice ofagent is controversial. Obstetricians havelong favored magnesium sulfate as thedrug of choice for prevention of recurrenteclamptic seizures, whereas neurologists fa-vor anticonvulsants traditionally used innonpregnant individuals, such as phenytoinor diazepam. This dispute appears to havebeen resolved by a number of recent clinicalstudies:

● The Eclampsia Trial Collaborative Groupconducted a prospective trial in which 905eclamptic women were randomly assigned toreceive either magnesium or diazepam and775 eclamptic women were randomly as-signed to receive either magnesium or phe-nytoin.16 Primary measures of outcome wererecurrence of seizures and maternal death.Women allocated to magnesium therapy hadhalf the rate of recurrent convulsions com-pared with those allocated to diazepam (13%and 28%, respectively). There were no sig-nificant differences in maternal or perinataldeath or complication rates between the twogroups. Similarly, women administered mag-nesium had one-third the rate of recurrent sei-zures of those taking phenytoin (6% vs. 17%).In this arm of the study, women who receivedmagnesium were 8% less likely to be admit-ted to an intensive care facility, 8% less likelyto require ventilatory support, and 5% lesslikely to develop pneumonia compared withwomen given phenytoin. There were no sig-nificant differences in the maternal death rateor perinatal outcome.

● A Cochrane review17 reported that magne-sium sulfate was safer and better than “lyticcocktail” (containing promethazine hydro-chloride, chlorpromazine, and meperidine hy-drochloride) for the prevention of repeat sei-zures in eclamptic women.

Additional advantages of magnesium sul-fate therapy include lower cost, ease of ad-

ministration (cardiac monitoring is not re-quired), and less sedation than diazepam andphenytoin. Magnesium also appears to se-lectively increase cerebral blood flow andoxygen consumption in women with pre-eclampsia18; this is not true for phenytoin.19

The maintenance dose of magnesium sul-fate is 2 to 3 g/h administered as a continu-ous intravenous infusion. The maintenancephase is given only if a patellar reflex is pres-ent (loss of deep tendon reflexes is the firstmanifestation of symptomatic hypermagne-semia), respirations are greater than 12 perminute, and urine output is greater than 100mL in 4 hours. Following serum magnesiumlevels is not required if the woman’s clinicalstatus is closely monitored for evidence ofpotential magnesium toxicity. There alsodoes not appear to be a clear threshold con-centration for ensuring the prevention ofconvulsions, although a range of 4.8 to 8.4mg/dL has been recommended.20 The doseshould be adjusted according to the clinicalresponse of the patient (Table 2).

Evaluation for DeliveryThe definitive treatment of eclampsia isprompt delivery, irrespective of gestationalage, to prevent potential maternal and fetalcomplications. However, this does not nec-essarily preclude induction of labor.21 Aftermaternal stabilization, several factorsshould be considered before determining themost appropriate route of delivery. These in-clude gestational age, Bishop score, and fe-tal condition and position. In general, lessthan one third of women with severepreeclampsia/eclampsia remote from term(<32 weeks’ gestation) with an unfavorablecervix will have a successful vaginal deliv-ery.22–24 Cervical ripening agents can beused to improve the Bishop score; however,long inductions should be avoided.

Fetal bradycardia lasting at least 3 to 5minutes is a common finding during and im-mediately after an eclamptic seizure anddoes not necessitate emergent cesarean de-livery. Maneuvers to stabilize the mothermay help the fetus recover in utero from the


effects of maternal hypoxia, hypercarbia,and uterine hyperstimulation. Resolution ofmaternal seizure activity is often associatedwith compensatory fetal tachycardia andeven with transient fetal heart rate decelera-tions, which typically resolve within 20 to30 minutes.25

PROGNOSISMaternal complications occur in up to 70%of women with eclampsia and include DIC,acute renal failure, hepatocellular injury,liver rupture, intracerebral hemorrhage, car-diorespiratory arrest, aspiration pneumoni-tis, acute pulmonary edema, and postpartumhemorrhage.26,27 Hepatocellular damage,renal dysfunction, coagulopathy, hyperten-sion, and neurologic abnormalities typicallyresolve after delivery. However, cerebro-vascular damage from hemorrhage or ische-mia may result in permanent neurologic se-quelae.28

Maternal death rates of 0–13.9% havebeen reported.7,26,28 One retrospectiveanalysis of 990 cases of eclampsia found anoverall maternal death rate of 13.9%(138/990). The highest risk (12/54 [22%])was observed in a subgroup of women witheclampsia previous to 28 weeks’ gestation.Maternal death and severe complicationrates are lowest among women receivingregular prenatal care who are managed byexperienced physicians in tertiary cen-ters.29,30 An autopsy study performedshortly after death in eclamptic women

found that the brains of more than 50% ofthe women who died within 2 days of sei-zures displayed cerebral hemorrhages andsoftening.31 Petechial cortical hemorrhageswere most common, especially involvingthe occipital lobe. Diffuse cerebral edemaand gross hemorrhage were noted less fre-quently. Cerebral venous thrombosis wascommon in woman with postpartumeclampsia.

The perinatal death rate in eclampticpregnancies is 9–23%7,26 and is closely re-lated to gestational age. For example, theperinatal death rate in one series of 54 par-turients with eclampsia before 28 weeks’gestation was 93%26; this rate was only 9%in another study in which the mean gesta-tional age at birth was 32 weeks.32 Perinataldeaths are primarily the result of prematuredelivery, abruptio placentae, and intrauter-ine asphyxia.

FUTURE PREGNANCIESEclampsia can recur in a subsequent preg-nancy.33,34 The risk appears to be reducedby close maternal monitoring and timely in-tervention if preeclampsia develops.35 How-ever, there is as yet no effective way to pre-vent preeclampsia.36 The rate of recurrenteclampsia is estimated to be around 2%.37

Subsequent pregnancies in women with ahistory of severe preeclampsia/eclampsiaare also at increased risk of other obstetriccomplications compared with women withno such history, including placental abrup-

TABLE 2. Prevention of Recurrent Seizures in Patients With Eclampsia

Drug Loading Dose Maintenance Dose Therapeutic Level

Recommended first-line therapyMagnesium sulfate 4–6 g IV over 10–20 min 2–3 g/h IV infusion 4–8 mEq/L*

10 g IM (5 g into each buttock) 5 g IM every 4 h As above

Recommended therapy in women refractory to magnesium sulfatePhenytoin 1–1.5 g IV over 1 h (depending on

body weight)250–500 mg q 10–12 h

orally or IV10–20 µg/mL

Diazepam – 10 mg/h IV infusion –Chlormethiazole† 40–100 mL of 0.8% over 20 min 60 mL/h IV infusion –

* Not tested prospectively

† Not available in the United States

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tion (2.5–6.5% vs. 0.8%), preterm delivery(15–21% vs. 7–8%), intrauterine growth re-striction (12–23% vs. 10%), and an in-creased perinatal death rate (4.6–16.5% vs.1–3%).32,33,38,39 Women with a history ofpreeclampsia/eclampsia remote from term(<28 weeks’ gestation) are at highest risk fordeveloping these complications.38,39 Thisrisk appears to be the same whether they hadsevere preeclampsia or eclampsia.

CAN ECLAMPSIA BE PREDICTED?The relationship between hypertension,signs and symptoms of cortical irritability(headache, visual aberrations, nausea, vom-iting, fever, hyperreflexia), and seizures re-mains unclear. A retrospective analysis of383 cases of eclampsia in the United King-dom found that only 59% of eclampticwomen experienced one or more prodromalsymptoms—headache, visual disturbance(scotomata, amaurosis, blurred vision, dip-lopia, homonymous hemianopsia), or epi-gastric pain—before their eclamptic sei-zure.7 Moreover, the magnitude of bloodpressure elevation does not appear to be pre-dictive of eclampsia, although it does corre-late well with the incidence of cerebrovas-cular accident. Retrospective analysisshows that eclampsia was the first manifes-tation of pregnancy-related hypertensivedisease in 20–38% of cases.7,28 Similar find-ings were reported in studies from Sweden,Scotland, and the United States.40–42 In oneof the latter reviews, the factors found to beat least partially responsible for failure toprevent eclampsia (179 consecutive cases)were physician error (36%), magnesiumfailure (13%), late postpartum onset (12%),early onset before 21 weeks (3%), abrupt on-set (18%), and lack of prenatal care (19%).41

Therefore, many cases of eclampsia appearnot to be preventable, even among womenreceiving regular prenatal care.

PREVENTION OF FIRST ECLAMPTICSEIZUREAlthough not all cases of eclampsia can bepredicted, anticonvulsant therapy adminis-

tered to parturients at high risk can prevent afirst seizure in women with severe pre-eclampsia. Two large studies have demon-strated the superiority of magnesium sulfateover phenytoin for the prevention ofeclampsia.43,44 The Parkland Hospitalgroup, for example, randomly assigned2,138 preeclamptic women to receive eithermagnesium or phenytoin.43 Eclamptic sei-zures developed in 10 of 1,089 women as-signed to phenytoin compared with none of1,049 women assigned to magnesium (P =0.004). Maternal and neonatal outcomeswere similar in both groups. These data aresupported by a recent study performed inSouth Africa in which 685 women with se-vere preeclampsia were randomly assignedto seizure prophylaxis with magnesium sul-fate therapy or placebo.45 Progression toeclampsia was lower in the magnesiumgroup (0.3% vs. 3.2% [P = 0.003]).

Anticonvulsant therapy is generally initi-ated during labor or while administering an-tenatal corticosteroid therapy or cervical rip-ening agents previous to planned delivery inwomen with severe preeclampsia. Treat-ment should be continued until 24 to 48hours postpartum, when the risk of seizuresis low. The most common magnesium sul-fate regimen is a loading dose of 4 to 6 ggiven intravenously over 20 minutes, fol-lowed by 2 to 3 g/h as a continuous infusion.It is unclear whether all women with pre-eclampsia require prophylaxis to preventseizures in a small number of patients (0.6–3.2%46). Moreover in women with nonpro-teinuric hypertension, the incidence of sei-zures is so low (<0.1%45) that it may be safeto withhold seizure prophylaxis in such women.

HELLP SyndromeHELLP syndrome (hemolysis, elevatedliver enzymes, low platelets) is a seriouscomplication of preeclampsia that was firstdescribed by Pritchard et al in 1954,47 al-though the term HELLP syndrome wascoined by Weinstein in 1982.48 Amongwomen with severe preeclampsia, 6% will


manifest with one abnormality suggestive ofHELLP syndrome (usually elevated liverenzymes or low platelets), 12% will developtwo abnormalities, and about 10% willmanifest with all three abnormalities.49

HELLP syndrome can manifest at any timeduring pregnancy and the puerperium but(like preeclampsia) is rare before 20 weeks’gestation. One third of all cases of HELLPsyndrome occur postpartum, and only 80%of such patients were diagnosed with pre-eclampsia before delivery.

CLINICAL MANIFESTATIONS ANDDIAGNOSISAlthough parturients with HELLP syn-drome may be asymptomatic, 80% reportright upper quadrant pain and 50–60% pre-sent with excessive weight gain and worsen-ing edema. Not all women with HELLP syn-drome have hypertension or proteinuria.Indeed, 20% of patients with HELLP syn-drome have a maximum blood pressure lessthan 140/90 mm Hg, and 6% do not havesignificant proteinuria at the time of diagno-sis.49 Other clinical conditions that shouldbe considered in women with features sug-gestive of HELLP syndrome include hemo-lytic uremic syndrome, thrombotic throm-bocytopenic purpura, and acute fatty liver.

The definitive laboratory criteria for thediagnosis of HELLP syndrome remain to bevalidated prospectively. However, the labo-ratory criteria most commonly used arethose defined by Sibai in 1990.49 In this re-view, Sibai defined hemolysis as the pres-ence of an abnormal peripheral smear withschistocytes, serum lactate dehydrogenase(LDH) more than 600 U/L, and total biliru-bin more than 1.2 mg/dL; elevated liver en-zymes as serum aspartate aminotransferasemore than 70 U/L (>3 standard deviationsabove norm) and LDH more than 600 U/L;and low platelet count as less than100,000/mm3. Based on the severity of thethrombocytopenia, Martin et al50 furthercategorized HELLP syndrome into threeclasses. Class 1 is defined as a platelet countless than 50,000/mm3, class 2 as a platelet

count 50,000 to 100,000/mm3, and class 3 asa platelet count more than 100,000/mm3. Al-though this classification does appear to cor-relate to some degree with the prognosis andspeed of resolution, it is not widely ac-cepted.

ETIOLOGY AND PATHOPHYSIOLOGYLike preeclampsia, endothelial dysfunction,with resultant activation of the intravascularcoagulation cascade, has been proposed asthe central pathogenesis of HELLP syn-drome. However, unlike preeclampsia,HELLP syndrome occurs more often inwhites, in multipara, and in women olderthan 35 years. Some investigators regardHELLP syndrome as an entirely distinct dis-ease entity from preeclampsia.

When preeclampsia is complicated byHELLP syndrome, the maternal and perina-tal death rates are significantly increased.Reported maternal death rates are 0–24%;death results most often from liver rupture,DIC, acute renal failure, pulmonary edema,carotid thrombosis, and cerebrovascular ac-cident.51 Perinatal death is related mostclosely to complications of prematurity, fe-tal growth restriction, and placental abrup-tion. Reported perinatal death rates are 7.7–60%.51 Delayed diagnosis and delayed or in-appropriate treatment are commonly cited asreasons for the poor overall prognosis asso-ciated with HELLP syndrome. Early identi-fication of this syndrome, coupled withprompt and appropriate intervention, cansignificantly reduce maternal and perinataldeath and complication rates. Accordingly,parturients with HELLP syndrome shouldideally be managed in a tertiary care facility.

MANAGEMENTStabilization of the mother’s conditions andassessment of fetal well-being are the firstresponsibilities of management for parturi-ents with HELLP syndrome. Seizure pro-phylaxis should be administered in the formof parenteral magnesium sulfate. If the preg-nancy is less than 34 weeks, antenatal corti-costeroids should be given to enhance fetal

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lung maturation. With few exceptions, im-mediate delivery is indicated, irrespective ofgestational age. The decision of whether todelay delivery for 48 hours to complete a fullcourse of antenatal corticosteroids should beindividualized. Immediate delivery does notnecessarily mean cesarean delivery. How-ever, if the pregnancy is remote from term(<32 weeks) and the cervix is unfavorable,an elective cesarean delivery is a reasonableoption. Because the incidence of hematomaformation after cesarean delivery in womenwith HELLP syndrome may be as high as20%,49 it may be prudent to place one ormore subfascial and/or subcutaneous drainsat the time of surgery, especially if thereis evidence of significant intraoperativeoozing or severe thrombocytopenia(<50,000/mm3). The drains can be removedelectively in 24 to 48 hours. If the gestationalage is more than 34 weeks, induction of la-bor can be initiated with or without cervicalripening, if indicated. It is our usual practiceto check coagulation test results as well ashepatic and renal function test results every6 hours until delivery, and then daily untilstable.

Several specific therapeutic maneuvershave been proposed in an effort to cureor alleviate HELLP syndrome. These in-clude, among others, plasma volumeexpansion (using crystalloid or albumin),thrombolytic agents (low-dose aspirin, di-pyridamole, heparin, antithrombin III,prostacyclin/thromboxane synthetase in-hibitors), immunosuppressive agents (corti-costeroids), exchange plasmapheresis, anddialysis. Magann et al52 reported that ante-partum dexamethasone administration towomen with HELLP syndrome significantlyincreased maternal platelet count, decreasedserum alanine aminotransferase and LDH,increased maternal urine output, and re-sulted in a longer entry-to-delivery intervalcompared with women who did not receivecorticosteroids. A subsequent study by thesame group from the University of Missis-sippi Medical Center reported that dexa-methasone was more effective than beta-

methasone in the antepartum “treatment” ofHELLP syndrome.53 Of note, the dose ofdexamethasone recommended in these stud-ies for antepartum treatment of HELLP syn-drome (12 mg q12h until delivery) is signifi-cantly higher than that recommended by theNational Institutes of Health54 or the Ameri-can College of Obstetricians and Gynecolo-gists (ACOG) for promotion of fetal lungmaturity (6 mg q12h for 48 hours55). More-over, corticosteroid administration in thesestudies was by the intravenous rather thanthe intramuscular route, as recommendedby the National Institutes of Health54 andACOG.55 The effect of large doses of intra-venous corticosteroids on fetal adrenal func-tion and fetal development is not known. Assuch, expectant management and antepar-tum “treatment” of HELLP syndrome withlarge doses of corticosteroids is not univer-sally accepted.

In addition to antepartum corticosteroids,Magann et al56 have also reported on the useof postpartum intravenous corticosteroids(10 mg q12h for two doses followed by 5 mgq12h for two doses) to accelerate the rever-sal of HELLP syndrome. Although the fetaleffect of high-dose corticosteroids is nolonger a concern postpartum, larger ran-domized clinical trials are needed to verifythe efficacy of postpartum corticosteroidtherapy for HELLP syndrome. With or with-out corticosteroids, the vast majority ofwomen with HELLP syndrome will recoverwithin 96 hours of delivery.

FUTURE PREGNANCIESThe reported risk of recurrent HELLP syn-drome in a subsequent pregnancy rangesfrom 3%57 to 27%.58 Future pregnancies arealso at increased risk of other adverseevents, including other manifestations ofpreeclampsia, preterm delivery, fetal growthrestriction, placental abruption, and cesar-ean delivery. The overall risk of such com-plications is 19–43%.57,58


Liver RuptureLiver rupture is one of the most severe con-sequences of severe preeclampsia/HELLPsyndrome, with a reported maternal deathrate of more than 30%.59 It occurs mostcommonly in multiparas of advanced age.Fortunately, it is rare. The precise cause ofliver rupture remains unknown. The prevail-ing theory is that endothelial dysfunctionwith intravascular fibrin deposits and he-patic sinusoidal obstruction leads to intrahe-patic vascular congestion, increased intrahe-patic pressure, and distention of Glisson’scapsule, and finally to the development of asubcapsular hepatic hematoma and liverrupture.

CLINICAL MANIFESTATIONS ANDDIAGNOSISA high index of clinical suspicion is the keyto prompt and accurate diagnosis. Pain in theright upper quadrant and/or epigastric areaand focal tenderness are the most importantclinical features, especially if they occur inthe setting of preeclampsia/HELLP syn-drome. Bilateral shoulder-tip pain is sugges-tive of intraabdominal hemorrhage. Rarely,an abdominal mass may be palpated. If anabdominal mass is noted, further abdominalexaminations should be avoided becausesuch manipulations may cause the hema-toma to rupture. Imaging techniques such asultrasound, computed tomography (CT), ormagnetic resonance imaging (MRI) may en-able early and accurate diagnosis of liver he-matoma or rupture.

MANAGEMENTThe management of liver hematoma andrupture requires a multidisciplinary ap-proach in a tertiary care facility, if possible.The first priority is to stabilize the maternalhemodynamic status. Aggressive bloodtransfusion may be necessary. Immediateconsultation with a staff anesthesiologistand a general or vascular surgeon is indi-cated. If a liver hematoma is diagnosed inthe antepartum period without evidence of

rupture, an immediate exploratory laparoto-my and cesarean delivery should be per-formed. Unnecessary manipulation of theliver should be avoided because this mayprecipitate rupture. For the nonexpandingliver hematoma, surgical repair or evacua-tion is usually not necessary. Expectantmanagement with serial CT or abdominalultrasound examinations may be all that isneeded.

If there is evidence of liver rupture,prompt surgical intervention under generalendotracheal anesthesia is mandated. Atten-tion should be focused on the need for inva-sive hemodynamic monitoring and on bloodproduct replacement and correction of co-agulopathy, if indicated. After delivery ofthe fetus through a vertical skin incision, theupper abdomen should be explored. Thereare several approaches to the managementof liver rupture, and the decision of whichapproach to take depends on the hemody-namic status of the patient, the extent of therupture, the magnitude and rate of ongoinghemorrhage, and the experience of the sur-geons. Unlike repair of a traumatic liver lac-eration, simple suturing is rarely effectivebecause the entire liver is edematous and fri-able and the hepatic parenchyma does nothave the tensile strength to retain the su-tures.60 Other surgical options include pack-ing with gauze, topical coagulant agents orcollagen fleeces coated with fibrin glue, in-corporation of omental pedicles or surgicalmesh into the liver, ligation of the hepaticartery, radiologic embolization of the he-patic artery, or hepatic lobectomy. Hepaticartery embolization was recently reported tohave the highest maternal survival rate ofaround 90%61 and should be attempted ifhemorrhage can be controlled and if the pa-tient is hemodynamically stable.

The recurrence rate of liver rupture is un-determined, because only a few cases ofpregnancies in such women have been de-scribed. However, in all but one reported in-stance,62 there was no recurrence.

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Pulmonary EdemaPulmonary edema refers to an excessive ac-cumulation of fluid in the pulmonary inter-stitial and alveolar spaces. It complicatesaround 0.05% of low-risk pregnancies butmay develop in up to 2.9% of pregnanciescomplicated by preeclampsia.63

ETIOLOGY AND PATHOPHYSIOLOGYThe causes of pulmonary edema are oftenmultifactorial. According to the Starlingequation, any factor that results in a reduc-tion in colloid osmotic pressure (or in thecolloid osmotic pressure/pulmonary capil-lary wedge pressure gradient), an increase incapillary permeability, or an increase in in-travascular hydrostatic pressure will lead toextravasation of fluid from the vasculatureand predispose to the development of pul-monary edema.64

The underlying physiologic changes inthe maternal cardiovascular system that ac-company pregnancy predispose to the devel-opment of pulmonary edema. Such changesinclude an increase in plasma blood volume,cardiac output, heart rate, and capillary per-meability and a decrease in plasma colloidosmotic pressure. These changes are oftenexaggerated in the setting of preeclampsia,leading to a further increase in the incidenceof pulmonary edema. Moreover, in normalpregnancy, plasma colloid osmotic pressuredecreases from around 22 mm Hg at term to16 mm Hg after delivery (and from 18 mmHg at term to 14 mm Hg postpartum in preg-nancies complicated by preeclampsia65).The reduction in colloid osmotic pressureafter delivery may result from excessiveblood loss, fluid shifts secondary to in-creased capillary permeability (especially inpreeclamptic pregnancies), or excessivecrystalloid infusion. Such changes help toexplain at least in part why 70–80% of casesof pulmonary edema in the setting of pre-eclampsia develop after delivery.63,65 An-other confounding factor is magnesium sul-fate, which is often administered to pre-eclamptic women for seizure prophylaxis.To address this issue, Yeast et al66 measured

the effect of intravenous magnesium sulfateadministered for preterm labor or seizureprophylaxis on colloid osmotic pressure andthe risk for pulmonary edema in 294 preg-nant women. Only 4 of the 294 women de-veloped pulmonary edema, and all of themhad low colloid osmotic pressure in the set-ting of severe preeclampsia. The authorsconcluded that magnesium sulfate does notsignificantly change colloid osmotic pres-sure and, as such, does not pose a signifi-cantly increased risk of pulmonary edema.66

Only 30% of cases of pulmonary edemain the setting of preeclampsia occur beforedelivery.63 The vast majority (90%) of suchpatients have underlying chronic hyperten-sion, and they are more likely to be multipa-rous and of advanced maternal age.63 In thesetting of chronic hypertension with super-imposed preeclampsia, systemic vascularresistance and left heart filling pressures areincreased. This leads, in turn, to a decreasein cardiac output and an increase in pulmo-nary vascular hydrostatic pressure, whichculminates in the development of pulmo-nary edema. An additional feature that maypredispose to the development of pulmonaryedema in the setting of preeclampsia is anincrease in capillary leak and capillary fluidextravasation secondary to vascular endo-thelial damage.67

DIAGNOSISPulmonary edema is a clinical diagnosischaracterized by worsening dyspnea and or-thopnea along with signs of respiratory com-promise (tachypnea, auditory crackles andrales, hypoxemia). Arterial blood gas andchest x-ray may assist in the diagnosis. Inselect patients, electrocardiography,echocardiography, spiral CT imaging,ventilation/perfusion scan, or pulmonary ar-teriography may be necessary to excludeother causes of cardiopulmonary compro-mise, such as pulmonary embolism, pneu-monia, and cardiomyopathy.

MANAGEMENTPrompt diagnosis and intervention are man-datory. The goal of management is to stabi-


lize the mother, expedite resolution of thepulmonary edema, and then make a decisionabout delivery. Appropriate management ofacute pulmonary edema can be summarizedby the letters LMNOP:

● Lasix (furosemide) administered intrave-nously as a single dose of 20 to 40 mg over 2minutes to promote diuresis. If an adequateresponse is not seen within 30 to 50 minutes,the dose should be increased to 40 to 60 mgadministered by slow intravenous injection toa maximum of 120 mg in 1 hour. Electrolytes(especially potassium) should be supple-mented as needed.

● Morphine sulfate should be administered in-travenously at a dose of 2 to 5 mg as needed inan attempt to reduce the adrenergic vasocon-strictor stimuli to the pulmonary arteriolarand venous beds.

● Na+ (sodium) and water restriction, and strictinput/output monitoring.

● Oxygen supplementation using a non-rebreather face mask at 8 to 10 L/min, alongwith continuous monitoring of oxygen satura-tion using a pulse oximeter.

● Positioning (elevation) of the maternal headand chest to improve ventilation by reducingpulmonary capillary wedge pressure.

In addition to these standard measures, itis appropriate to follow the patient’s bloodpressure, electrocardiogram, and fetal heartrate tracing. Afterload reduction using a va-sodilator (eg, hydralazine, a calcium chan-nel blocker, or an angiotesin-1 convertingenzyme inhibitor [which should be usedonly after delivery]) may be necessary, es-pecially in parturients with chronic hyper-tension and superimposed preeclampsia.Because most obstetric patients have normalleft ventricular systolic function, inotropicsupport is rarely necessary. According toACOG, severe preeclampsia with pulmo-nary edema is one of the indications for in-vasive pulmonary artery catheterization,68

although most patients can be managed ini-tially without invasive hemodynamic moni-toring. However, if the pulmonary edema isrefractory to initial management or if it is ac-companied by persistent oliguria, insertion

of a pulmonary artery catheter and transferto an intensive care unit should be consid-ered. In patients with severe pulmonaryedema, mechanical ventilatory support maybe necessary.

In the setting of congestive heart failure,administration of a "-adrenergic antagonistmay be indicated. In the past, "-blockadewas considered contraindicated in patientswith congestive heart failure. However,more recent studies have shown that suchagents can antagonize the deleterious effectsof the sympathetic nervous system activa-tion that occurs in congestive heart failure.69

As such, "-blockade is now considered akey component of the management of acutecongestive heart failure. However, the use ofsuch agents in pregnancy and especially inpreeclampsia complicated by congestiveheart failure remains to be established.

Renal FailureAcute renal failure is characterized by anabrupt reduction in the maternal glomerularfiltration rate, leading to excessive retentionof urea and water as well as numerous elec-trolyte and acid-base abnormalities. Acuterenal failure is a rare complication of pre-eclampsia, but the actual incidence remainsundetermined. According to one center’sexperience, 18% of all cases of acute renalfailure were of obstetric origin.70 Amongthose patients, 20.9% of cases occurred inthe setting of preeclampsia. Other condi-tions that should be considered include he-molytic uremic syndrome, primary renovas-cular disease, and placental abruption.

ETIOLOGY AND PATHOGENESISThe characteristic histologic renal lesion inpreeclampsia is glomerular endotheliosis, inwhich the glomeruli are large and swollenwith vacuolated endothelial cells. This his-tologic feature, coupled with the generalizedvasoconstriction that characterizes pre-eclampsia, leads to a 25–30% decrease in re-nal plasma flow and glomerular filtrationcompared with normal pregnancy.71 How-

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ever, functional impairment of renal func-tion in women with preeclampsia is gener-ally mild and reverses completely after de-livery. As such, clinically significant acuterenal failure in preeclampsia is rare.

The causes of acute renal failure can bedivided into three broad categories: prerenal(which refers to renal hypoperfusion with-out parenchymal involvement), intrarenal(which suggests intrinsic renal parenchymaldamage), and postrenal (which implies ob-structive uropathy). Prerenal and intrarenalpathology (acute tubular necrosis) accountsfor 83–90% of all cases of acute renal failurein preeclampsia.72,73 Renal damage second-ary to these pathologic changes is seen mostcommonly in preeclampsia and usually re-solves completely after delivery. In contrast,bilateral renal cortical necrosis, which ac-counts for 10–29% of cases of acute renalfailure in pregnancy,72–74 is a far more seri-ous condition and is associated with signifi-cant rates of maternal and perinatal deathand complications. It is seen most com-monly in women with underlying chronichypertension and superimposed preeclamp-sia, known parenchymal renal disease, pla-cental abruption, or DIC.74

PROGNOSISIn 1990, Sibai et al72 reported on their expe-rience of the short-term pregnancy outcome,subsequent pregnancy outcome, and remoteprognosis in 31 patients with preeclampsiacomplicated by acute renal failure collectedover a period of 11 years. The actual inci-dence of acute renal failure could not be de-termined because most of their patients werereferred from outside institutions. The ma-ternal death rate was 10% (3/31). Overall, 14of their 31 patients (46.6%) required dialy-sis, and there was no difference in the per-centage of women requiring dialysis for pre-eclampsia (50%) and chronic hypertensionwith superimposed preeclampsia (42%). All18 patients with acute renal failure in the set-ting of preeclampsia had acute tubular ne-crosis, with complete resolution of renalfunction after delivery. In contrast, 3 of the

13 patients with chronic hypertension andsuperimposed preeclampsia had bilateralcortical necrosis; 9 of 11 (81.8%) survivingpatients required long-term dialysis, and 4had subsequently died of end-stage renaldisease before publication. The authors con-cluded that early identification and appro-priate management of acute renal failure inpreviously healthy parturients with pre-eclampsia did not result in residual long-term renal damage.

The same investigators from Memphis,Tennessee, subsequently reported their ex-perience with HELLP syndrome and acuterenal failure.75 The overall incidence ofacute renal failure in the setting of HELLPsyndrome was 7.3% in their cohort, with amaternal death rate of 13% and a perinataldeath rate of 34%. The majority of the 32patients with HELLP syndrome and acuterenal failure were postpartum. Furtheranalysis suggested that the presence of un-derlying chronic hypertension was associ-ated with a less favorable pregnancy out-come and a more guarded long-term progno-sis.

MANAGEMENTThe management of acute renal failure in thesetting of preeclampsia should focus on ex-cluding other diagnoses, especially condi-tions that may be reversible (eg, dehydra-tion or obstructive uropathy). Supportivetherapy includes blood pressure control, po-sitioning patients so as to improve renalblood flow, correcting fluid and electrolyteimbalance, and maintaining adequate nutri-tion. If dialysis is required in pregnancy, he-modialysis is preferred over peritoneal di-alysis.

Disseminated IntravascularCoagulopathyDIC is a hematologic disorder characterizedby a generalized increase in both fibrin for-mation and fibrinolysis, leading to excessiveconsumption of clotting factors, which


presents clinically as a bleeding diathesis.The most common causes of DIC in preg-nancy are excessive blood loss with inad-equate blood component replacement, pla-cental abruption, amniotic fluid embolism,and severe preeclampsia/HELLP syndrome.

DIAGNOSISDiagnosis requires a high index of suspicioncoupled with appropriate blood tests.Thrombocytopenia, which can be docu-mented in about 10% of parturients with se-vere preeclampsia,76 is often the first indica-tor of DIC. Moreover, a normal plateletcount effectively excludes the diagnosis.Other hematologic aberrations that can beused to confirm the diagnosis include an in-crease in circulating fibrin degradationproducts, D-dimer, platelet factor 4,"-thromboglobulin, thrombomodulin, fibri-nopeptide A, thrombin-antithrombin com-plexes, and a decrease in circulating anti-thrombin III, fibrinogen, and protein C ac-tivity. However, many of these tests areexpensive, time-consuming, and not clini-cally useful. Sibai et al77 defined DIC asevidence of excessive bleeding with throm-bocytopenia (<100,000/mm3), plasma fi-brinogen level less than 300/mg/dL, and fi-brin-split products more than 40 µg/mL. Us-ing this strict definition, they reported a 38%incidence of DIC in the setting of HELLPsyndrome.77 However, many pregnanciescompl ica ted by severe preec lamp-sia/HELLP syndrome have evidence of“subclinical” consumptive coagulopathywithout evidence of bleeding, suggestingthat DIC is a consequence, not a cause, ofpreeclampsia. Roberts and May,78 on theother hand, have argued that abnormal labo-ratory DIC parameters are rarely seen in se-vere preeclampsia/HELLP syndrome unlessthere is a concurrent placental abruption.Exactly which laboratory parameters tocheck is controversial. Metz et al79 havesuggested that the most practical and cost-effective approach to screening for con-sumptive coagulation in the setting of pre-

eclampsia is a combination of platelet countand activated partial thromboplastin time.

MANAGEMENTEvidence of DIC in the setting of severepreeclampsia/HELLP syndrome shouldprompt immediate delivery. The decision ofwhether to proceed with induction of laboror cesarean delivery depends on such factorsas gestational age, parity, cervical Bishopscore, motivation of the patient, and the se-verity of DIC (eg, a rapidly falling plateletcount may make cesarean delivery a moreappropriate choice). Moderate to severethrombocytopenia (especially a plateletcount <70,000/mm3) may be a contraindica-tion to regional anesthesia because of therisk of spinal hematoma.80

Because DIC is a consumptive coagu-lopathy and therefore a progressive condi-tion, early diagnosis and prompt and ap-propriate management are critical to reduc-ing maternal and perinatal death and com-plication rates. Heparin administration isnot generally recommended for the treat-ment of DIC in parturients with severepreeclampsia/HELLP syndrome.81 The cor-nerstones of management include mainte-nance of intravascular volume and replace-ment of blood components and/or coagula-tion factors, as indicated by laboratoryparameters. Each unit of packed red bloodcells has a volume of 250 mL and containscitrate-phosphate-dextrose as a preserva-tive. Packed red blood cells have a hemato-crit of about 70%, and in the absence of con-tinued hemorrhage, each unit should in-crease the hematocrit by 2–3% and thehemoglobin by about 1 g/dL in a healthy 70-kg (154-lb) woman.82 Fresh-frozen plasmacontains significant amounts of factors II (fi-brinogen), V, and VIII as well as providingadditional colloid support. Fresh-frozenplasma should be administered when theprothrombin time is at least 1.5-fold normal(ie, when the international normalized ratio[INR] is !1.5). The initial dose is usually 2units. Each unit has a volume of 200 to 250mL and raises circulating clotting factors by

320 NORWITZ ET AL

about 2–3%.82 Cryoprecipitate refers to aconcentrated extract of fresh-frozen plasmathat is enriched with factors II (fibrinogen)and VIII. Each unit has a volume of only 10to 15 mL. Transfusion of cryoprecipitateshould be considered when circulating fi-brinogen levels drop below 100 mg/dL inthe setting of DIC. When to recommendplatelet transfusion, however, is controver-sial. Some authorities have suggested thatplatelets be administered routinely if thecirculating platelet count is less than20,000/mm3 or if the platelet count is lessthan 50,000/mm3 if a surgical procedure isplanned, if there is active bleeding, or ifmassive transfusion is anticipated.82 Otherpractitioners note that such threshold recom-mendations are arbitrary and that platelettransfusion can usually be avoided evenwhen platelet counts are below these val-ues.83 However, in such circumstances, it isusually prudent to have platelets immedi-ately available in the event a platelet trans-fusion is needed. Platelets are prepared in avolume of 40 mL containing a total of 55 ×109 platelets. One unit of platelet concen-trate will usually increase the platelet countby 5,000 to 10,000/mm3. The usual dosageis 1 unit per 10 kg body weight.82 Smallamounts of erythrocytes are present in plate-let concentrates. If ABO and Rh type-specific platelets are not available, an Rh-negative woman can be sensitized by Rh-positive platelets. Anti-D immune globulin(RhoGAM) should be administered, if indi-cated.

Hypertensive EmergenciesHypertensive emergencies may complicatepreeclampsia as well as chronic hyperten-sion. Although the pathophysiology may bedifferent, the approach to acute evaluationand management is the same, with the prin-cipal goal being avoidance of hypertensiveencephalopathy and cerebrovascular acci-dent. Less clear is whether aggressive con-trol of blood pressure reduces the risk ofeclampsia. Although rare, cerebrovascular

accident as a result of acute hypertension isthe leading cause of maternal death in pre-eclampsia.84

DIFFERENTIAL DIAGNOSISAcute hypertension may be the result of anyone of a number of disorders. Although theetiology is usually apparent, considerationshould be given to diagnostic possibilitiesother than preeclampsia if the clinical pre-sentation is atypical. Such alternative diag-noses include pheochromocytoma, renalvein thrombosis, clonidine withdrawal, co-caine ingestion, methamphetamine inges-tion, and acute flare of an underlying colla-gen vascular disease. In most instances,however, the cause of acute hypertension isthe result of either worsening of underlyingessential hypertension or acute exacerbationof preeclampsia.

PATHOPHYSIOLOGYWhy hypertensive emergencies occur insome patients and not others remains un-clear. Some authorities have attempted todefine threshold parameters for hyperten-sive crisis and have suggested that a diastol-ic blood pressure of more than 115 mm Hgand/or a systolic blood pressure of more than200 mm Hg should be used to define hyper-tensive crisis.85,86 However, clinical experi-ence has shown that cerebrovascular acci-dent can occur in women whose blood pres-sure has remained consistently below thesethreshold parameters. Others have proposedthat it is the rate of blood pressure change,rather than an absolute measurement, that isresponsible for the cerebral injury.85

Hypertensive crises can affect numerousorgan systems. Retinal detachment and/orhemorrhage, congestive heart failure, myo-cardial infarction, renal failure, liver failure,placental abruption, and hypertensive en-cephalopathy may all result from acute anduncontrolled hypertension. Clinical evi-dence of any of the above end-organ effectsshould prompt a rapid response, with effortsdirected at blood pressure control. Most pa-tients may be managed without using inva-


sive hemodynamic monitoring, but patientswith severe or atypical cases are best man-aged in a tertiary center with such monitor-ing under the direction of clinicians skilledin critical care medicine.

MANAGEMENTHypertensive emergencies in pregnancypresent a significant clinical challenge. Themost important first step in the managementof hypertensive crisis is to lower blood pres-sure. Dramatic and rapid lowering of bloodpressure should be avoided. Ideally, an ini-tial reduction of blood pressure of about20%, with systolic and diastolic pressuregoals of 140 to 150 mm Hg and 90 to 100mm Hg, respectively, will provide the mostfavorable outcome.87 Hypertension refrac-tory to medical therapy is an indication forurgent termination of the pregnancy, and, inextreme circumstances, perimortem cesar-ean delivery may be necessary.85

In acute hypertension complicated by hy-pertensive encephalopathy, management

must occur in an intensive care facility. In-travenous sodium nitroprusside is the anti-hypertensive agent of choice in this setting.At doses exceeding 8 µg/kg per minute, con-cerns about cyanide and thiocyanate accu-mulation in the fetal compartment have beenexpressed. As such, close monitoring of cya-nide levels in patients receiving high dosesof sodium nitroprusside for extended peri-ods is recommended. Other medications thatmay be used in this setting to acutely lowerblood pressure are summarized in Table 3.

The definitive management of hyperten-sive crisis in the setting of preeclampsia isdelivery. Regional analgesia and anesthesiaare preferred in this setting, provided there isno evidence of coagulopathy and no othercontraindications to regional anesthesia.Avoidance of hypotension is critical in thesepatients. If general anesthesia is needed,blood pressure control is essential, and pre-medication may be necessary to avoid theincrease in blood pressure that often accom-panies induction of general anesthesia.

TABLE 3. Pharmacologic Management of Acute Hypertensive Crisis

Drug Dosing Comment

Recommended First-Line TherapyHydralazine 5 mg IV push q 10 min × 2 doses; then

10 mg IV push q 20 min as neededuntil blood pressure has stabilized at140–150/90–100 mm Hg

Be aware of hypotension andpotential to adversely effectuteroplacental perfusion.

Labetalol 10–20 mg IV push; repeat q 10–20 minwith doubling doses (not to exceed80 mg in any single dose) to amaximum of 300 mg total

Be aware of hypotension andpotential to adversely effectuteroplacental perfusion.

Nifedipine 10 mg orally q 30 min × 2 doses; then10–20 mg orally q 4–6 hourly

Sublingual nifedipine is bestavoided.*

Recommended Therapy in Women Refractory to First-Line AgentsSodium nitroprusside 0.5–3.0 µg/kg/min IV infusion (not to

exceed 800 µg/min)Should be used only by someone

with critical care experienceNitroglycerin 5 µg/min IV infusion, increase as

required every 5 min to maximumdose of 100 µg/min

Relatively contraindicated in thesetting of hypertensiveencephalopathy as it may increasecerebral blood flow andintracranial pressure*

Adapted from Repke JT. Preeclampsia and hypertension. In: Repke JT, ed. Intrapartum Obstetrics. New York: Churchill Livingstone,1996:271.

* Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hyper-tensive emergencies and pseudoemergencies? JAMA. 1996; 276:1328–1331.

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Hypertensive Encephalopathyand Cortical BlindnessCortical blindness is a known complicationof severe preeclampsia. Other ophthalmo-logic manifestations of preeclampsia in-clude retinal detachment, retinal arteriolarvasospasm, and thrombosis of the centralretinal arteries.88,89 The incidence of corti-cal blindness as a manifestation of hyperten-sive encephalopathy in severe preeclampsiais 1–15%.90,91

PATHOPHYSIOLOGYThe brain is normally protected from ex-tremes of blood pressure by an autoregula-tory system that ensures constant perfusionover a wide range of systemic pressures. Inresponse to systemic hypotension, cerebralarterioles dilate to maintain adequate perfu-sion, whereas vessels constrict in responseto high systemic pressures. Above the upperlimit of autoregulation, hypertensive en-cephalopathy may develop.92 Hypertensiveencephalopathy is a subacute neurologicsyndrome characterized by headache, sei-zures, visual aberrations, and other neuro-logic disturbances (altered mental status, fo-cal neurologic signs) in the setting of el-evated blood pressure. Although thesyndrome is usually reversible if the hyper-tension is treated early, it may be fatal if it isunrecognized or if treatment is delayed.93,94

The clinical findings are nonspecific and thediagnosis may be difficult to establish, par-ticularly in patients who have other ill-nesses. Various neurologic conditions suchas cerebrovascular accident, venous throm-bosis, and encephalitis can mimic hyperten-sive encephalopathy.95 Radiologic imagingstudies may be useful in establishing the di-agnosis in the appropriate clinical setting.96

The classic autopsy studies of Sheehanand Lynch97 in the 1960s refuted the pre-vailing opinion that preeclampsia/eclampsiawas frequently associated with widespreadcerebral edema. The most common lesionsdescribed were multiple petechial hemor-rhages in the cortex, subcortical region,

white matter, and midbrain. Because pete-chial hemorrhages were associated withcapillary thrombi, the authors concludedthat the lesions were caused by a vasculardisturbance that produced local ischemia.Severe diffuse cerebral edema is occasion-ally seen in eclampsia; however, the moretypical lesion is localized edema at the graymatter/white matter junction in the occipitallobe. The susceptibility of the posterior cir-culation to the lesions of hypertensive en-cephalopathy is a well-known but poorly un-derstood phenomenon.98,99 One possibleexplanation involves the regional heteroge-neity of the sympathetic vascular innova-tion. In experimental studies, the sympa-thetic innervation of the intracranial arteri-oles has been shown to protect the brainfrom marked increases in blood pressure.100

Moreover, ultrastructural studies haveshown that the internal carotid system ismuch better supplied with sympathetic in-nervation than is the vertebrobasilar sys-tem.101 Acute hypertension would, accord-ing to this hypothesis, stimulate the perivas-cular sympathetic nerves, which wouldprotect the anterior but not the more poorlyinnervated posterior circulation. This wouldresult in breakthrough of autoregulationwith edema mainly in the occipital lobes,and resultant ophthalmologic manifesta-tions.

Two theories have been proposed to ac-count for the clinical and radiologic abnor-malities associated with hypertensive en-cephalopathy and cortical blindness. Thefirst postulates that hypertensive encepha-lopathy results from spasm of the cerebralvasculature in response to acute hyperten-sion, resulting in ischemic injury, arteriolarnecrosis, and cytotoxic edema.102–105 Amore recent alternative hypothesis suggeststhat the syndrome results from breakthroughof autoregulation with passive overdisten-tion of cerebral arterioles, leading to in-creased capillary permeability with leakageof fluid and proteins into the surrounding tis-sues, resulting in vasogenic (hydrostatic)edema.92,96,106 In both instances, the end re-


sult is focal cerebral edema. The presence ofcerebral edema on head CT or MRI is there-fore not helpful in defining the mechanismunderlying hypertensive encephalopathy.The availability of improved neuroimaging,including single-photon emission computedtomography (SPECT), which can distin-guish between areas of hyper- and hypoper-fusion, has enabled a more detailed investi-gation of the response of the cerebral vascu-lature to hypertension.

In 1992, Schwartz et al96 reported on theuse of CT, MRI, and SPECT in 14 patientswith hypertensive encephalopathy, includ-ing 8 with preeclampsia. All patients had hy-podense lesions in the occipital lobes on CT,which correlated with lesions of increasedsignal intensity on T2-weighted MRI.SPECT performed on two patients duringhypertensive episodes revealed areas of in-creased cerebral perfusion, which corre-sponded with lesions on CT and MRI. Thesedata support the concept that hypertensiveencephalopathy results primarily from in-creased capillary permeability leading to va-sogenic edema. If vasospasm and resultantischemia were important features, decreasedcerebral perfusion on SPECT would havebeen observed with possible infarction.However, infarction is a rare occurrenceboth clinically93,96,98,103,104 and experimen-tally.107

MANAGEMENTCortical blindness and other manifestationsof hypertensive encephalopathy are a con-traindication to expectant management ofpreeclampsia in pregnancy. Delivery of thefetus and placenta remains the only curativetreatment. Other responsibilities of manage-ment include exclusion of other causes ofblindness (eg, occipital hemorrhage andretinal detachment) and aggressive bloodpressure control. Cortical blindness will re-verse completely after delivery, althoughresolution may take many weeks.96,106

ConclusionPreeclampsia remains a significant cause ofmaternal and perinatal death and complica-tions. Once the diagnosis of preeclampsiahas been made, treatment options are lim-ited. For this reason, much attention has re-cently been focused on preeclampsia pre-vention. Despite an extensive research ef-fort, no single strategy has yet been shown tobe beneficial in preventing the developmentof preeclampsia in either low- or high-riskpopulations.36 Preeclampsia is a disorder ofplacental implantation and is therefore notentirely preventable. Delivery of the fetusand placenta remains the only curative treat-ment. A healthy respect for this condition,coupled with aggressive and early interven-tion in the event of preeclampsia complica-tions, may be able to minimize adverse ma-ternal and perinatal events in the setting ofsevere preeclampsia.

References1. American College of Obstetricians and

Gynecologists. Hypertension in preg-nancy. ACOG Technical Bulletin No. 219.Washington, DC: ACOG, 1996.

2. Meekins JW, Pijnenborg R, Hanssens M,et al. A study of placental bed spiral arter-ies and trophoblast invasion in normal andsevere pre-eclamptic pregnancies. Br J Ob-stet Gynaecol. 1994;101:669–674.

3. Report of the National High Blood Pres-sure Education Program Working Groupon high blood pressure in pregnancy. Am JObstet Gynecol. 2000;183:S1-S22.

4. Morriss MC, Twickler DM, Hatab MR, etal. Cerebral blood flow and cranial mag-netic resonance imaging in eclampsia andsevere preeclampsia. Obstet Gynecol.1997;89:561.

5. Rochat RW, Koonin LM, Atrash HF, et al.Maternal mortality in the United States:Report from the Maternal Mortality Col-laborative. Obstet Gynecol. 1988;72:91.

6. Duley L. Maternal mortality associatedwith hypertensive disorders of pregnancyin Africa, Asia, Latin America and the Ca-ribbean. Br J Obstet Gynaecol. 1992;99:547.

324 NORWITZ ET AL

7. Douglas KA, Redman CW. Eclampsia inthe United Kingdom. Br Med J. 1994;309:1395.

8. World Health Organization InternationalCollaborative Study of Hypertensive Dis-orders of Pregnancy. Geographic variationin the incidence of hypertension in preg-nancy. Am J Obstet Gynecol. 1988;158:80.

9. Dahmus MA, Barton JR, Sibai BM. Cere-bral imaging in eclampsia: Magnetic reso-nance imaging versus computed tomogra-phy. Am J Obstet Gynecol. 1992;167:935.

10. Miles JF Jr, Martin JN Jr, Blake PG, et al.Postpartum eclampsia: A recurring perina-tal dilemma. Obstet Gynecol. 1990;76:328.

11. Lubarsky SL, Barton JR, Friedman SA, etal. Late postpartum eclampsia revisited.Obstet Gynecol. 1994;83:502.

12. Roberts JM. Magnesium for preeclampsiaand eclampsia. N Engl J Med. 1995;333:250.

13. Delgado-Escueta AV, Wasterlain C,Treiman DM, et al. Current concepts inneurology: management of status epilepti-cus. N Engl J Med. 1982;306:1337.

14. Lindenstrom E, Boysen G, Nyboe J. Influ-ence of systolic and diastolic blood pres-sure on stroke risk: a prospective observa-tional study. Am J Epidemiol. 1995;142:1279.

15. Pritchard JA, Cunningham FG, PritchardSA. The Parkland Memorial Hospital pro-tocol for treatment of eclampsia: evalua-tion of 245 cases. Am J Obstet Gynecol.1984;148:951.

16. Which anticonvulsant for women witheclampsia? Evidence from the Collabora-tive Eclampsia Trial. Lancet. 1995;345:1455.

17. Duley L, Gulmezoglu AM. Magnesiumsulphate versus lytic cocktail for eclampsia(Cochrane Review). Cochrane DatabaseSyst Rev 2001;1:CD002960.

18. Belfort MA, Moise KJ Jr. Effect of magne-sium sulfate on maternal brain blood flowin preeclampsia: A randomized, placebo-controlled study. Am J Obstet Gynecol.1992;167:661.

19. Gerthoffer WT, Shafer PG, Taylor S. Se-lectivity of phenytoin and dihydropyridinecalcium channel blockers for relaxation of

the basilar artery. J Cardiovasc Pharmacol.1987;10:9.

20. Sibai BM, Lipshitz J, Anderson GD, et al.Reassessment of intravenous MgSO4therapy in preeclampsia-eclampsia. ObstetGynecol. 1981;57:199.

21. American College of Obstetricians andGynecologists. Induction of labor. ACOGPractice Bulletin No. 10. Washington, DC:ACOG, 1999.

22. Alexander JM, Bloom SL, McIntire DD, etal. Severe preeclampsia and the very lowbirth weight infant: is induction of laborharmful? Obstet Gynecol. 1999;93:485.

23. Nassar AH, Adra AM, Chakhtoura N, et al.Severe preeclampsia remote from term:Labor induction or elective cesarean deliv-ery? Am J Obstet Gynecol. 1998;179:1210.

24. Pritchard JA, Cunningham FG, PritchardSA. The Parkland Memorial Hospital pro-tocol for treatment of eclampsia: Evalua-tion of 245 cases. Am J Obstet Gynecol.1984:148:951.

25. Paul RH, Koh KS, Bernstein SG. Changesin fetal heart rate-uterine contraction pat-terns associated with eclampsia. Am J Ob-stet Gynecol. 1978;130:165.

26. López-Llera M. Main clinical types andsubtypes of eclampsia. Am J Obstet Gyne-col. 1992;166:4.

27. Sibai BM, Spinnato JA, Watson DL, et al.Eclampsia. IV. Neurological findings andfuture outcome. Am J Obstet Gynecol.1985;152:184.

28. Sibai BM, McCubbin JH, Anderson GD, etal. Eclampsia. I. Observations from 67 re-cent cases. Obstet Gynecol. 1981;58:609.

29. Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254 consecutivecases. Am J Obstet Gynecol. 1990;163:1049.

30. Conde-Agudelo A, Kafury-Goeta AC.Case-control study of risk factors for com-plicated eclampsia. Obstet Gynecol. 1997;90:172.

31. Sheehan HL, Lynch JB. Pathology of tox-aemia of pregnancy. Baltimore: Williams& Wilkins, 1973.

32. Sibai BM, Anderson GD, Abdella TN, etal. Eclampsia. III. Neonatal outcome,growth, and development. Am J ObstetGynecol. 1983;146:307.


33. Chesley LC, Annitto JE, Cosgrove RA.The remote prognosis of eclampticwomen. Am J Obstet Gynecol. 1976;124:446.

34. Sibai BM, el-Nazer A, Gonzalez-Ruiz A.Severe preeclampsia-eclampsia in youngprimigravid women: Subsequent preg-nancy outcome and remote prognosis. AmJ Obstet Gynecol. 1986;155:1011.

35. Gilstrap LC, 3rd, Cunningham FG, Whal-ley PJ. Management of pregnancy-inducedhypertension in the nulliparous patient re-mote from term. Semin Perinatol. 1978;2:73.

36. Norwitz ER, Robinson JN, Repke JT. Pre-vention of preeclampsia: Is it possible?Clin Obstet Gynecol. 1999;42:436–54.

37. Sibai BM, Sarinoglu C, Mercer BM.Eclampsia. VII. Pregnancy outcome aftereclampsia and long-term prognosis. Am JObstet Gynecol. 1992;166:1757.

38. Sibai BM, Mercer B, Sarinoglu C. Severepreeclampsia in the second trimester: re-currence risk and long-term prognosis. AmJ Obstet Gynecol. 1991;165:1408.

39. Sibai BM, Ramadan MK, Chari RS, et al.Pregnancies complicated by HELLP syn-drome (hemolysis, elevated liver enzymes,and low platelets): subsequent pregnancyoutcome and long-term prognosis. Am JObstet Gynecol. 1995;172:125.

40. Moller B, Lindmark G. Eclampsia in Swe-den, 1976–1980. Acta Obstet GynecolScand. 1986;65:307.

41. Sibai BM, Abdella TN, Spinnato JA, et al.Eclampsia. V. The incidence of nonpre-ventable eclampsia. Am J Obstet Gynecol.1986;154:581.

42. Campbell DM, Templeton AA. Is eclamp-sia preventable? In: Bonnar J, MacGil-livray I, Symonds ED, eds. Pregnancy Hy-pertension. Baltimore: University ParkPress, 1980:483.

43. Lucas MJ, Leveno KJ, Cunningham FG. Acomparison of magnesium sulphate withphenytoin for the prevention of eclampsia.N Engl J Med. 1995;333:201.

44. Which anticonvulsant for women witheclampsia? Evidence from the Collabora-tive Eclampsia Trial. Lancet. 1995;345:1455.

45. Coetzee EJ, Dommisse J, Anthony J. Arandomised controlled trial of intravenous

magnesium sulphate versus placebo in themanagement of women with severe pre-eclampsia. Br J Obstet Gynaecol. 1998;105:300.

46. Hall DR, Odendaal HJ, Smith M. Is theprophylactic administration of magnesiumsulphate in women with preeclampsia indi-cated prior to labour? Br J Obstet Gynae-col. 2000;107:903.

47. Pritchard JA, Weissman R, Ratnoff OD, etal. Intravascular hemolysis, thrombocyto-penia, and other hematologic abnormali-ties associated with severe toxemia ofpregnancy. N Engl J Med. 1954;250:89–98.

48. Weinstein L. Syndrome of hemolysis, el-evated liver enzymes, and low plateletcount: A severe consequence of hyperten-sion in pregnancy. Am J Obstet Gynecol.1982;142:159–167.

49. Sibai BM. The HELLP syndrome (hemo-lysis, elevated liver enzymes, and lowplatelets): Much ado about nothing? Am JObstet Gynecol. 1990;162:311–316.

50. Martin JN Jr, Blake PG, Lowry SL, et al.Pregnancy complicated by preeclampsia-eclampsia with the syndrome of hemoly-sis, elevated liver enzymes, and low plate-let count: how rapid is postpartum recov-ery? Obstet Gynecol. 1990;76:737–741.

51. Sibai BM. Hypertension. In: Gabbe SG,Niebyl JR, Simpson JL, eds. Obstetrics:Normal and Problem Pregnancies, 4th ed.Philadelphia: Churchill Livingstone,2002:945–1004.

52. Magann EF, Bass D, Chauhan SP, et al.Antepartum corticosteroids: Disease stabi-lization in patients with the syndrome he-molysis, elevated liver enzymes, and lowplatelets (HELLP). Am J Obstet Gynecol.1994;171:1148–1153.

53. Isler CM, Barrilleaus PS, Magann EF, et al.A prospective, randomized trial comparingthe efficacy of dexamethasone and beta-methasone for the treatment of antepartumHELLP (hemolysis, elevated liver en-zymes, and low platelet count) syndrome.Am J Obstet Gynecol. 2000;184:1332–1337.

54. Effect of antenatal steroids for fetal matu-ration on perinatal outcomes. NIH Consen-sus Statement. 1994 Feb 28–March2;12:1–24.

326 NORWITZ ET AL

55. American College of Obstetricians andGynecologists. Antenatal corticosteroidtherapy for fetal maturation. ACOG Com-mittee Opinion No. 210, 1998.

56. Magann EF, Perry KG Jr, Meydrech EF, etal. Postpartum corticosteroids: Acceler-ated recovery from the syndrome of hemo-lysis elevated liver enzymes, and lowplatelets (HELLP). Am J Obstet Gynecol.1994;171:1154–1158.

57. Sibai BM, Ramadan MK, Chari RS, et al.Pregnancies complicated by HELLP syn-drome (hemolysis, elevated liver enzymes,and low platelets): Subsequent pregnancyoutcome and long-term prognosis. Am JObstet Gynecol. 1995;172:125–129.

58. Sullivan CA, Magann EF, Perry KG Jr.The recurrence of the syndrome of hemo-lysis, elevated liver enzymes, and lowplatelets (HELLP. in subsequent gesta-tions. Am J Obstet Gynecol. 1994;171:940–943.

59. Smith LG Jr, Moise KF Jr, Dildy GA III, etal. Spontaneous rupture of liver duringpregnancy: Current therapy. Obstet Gyne-col. 1991;77:171–175.

60. Lucas CE, Ledgerwood AM. Prospectiveevaluation of hemostatic techniques forliver injuries. J Trauma. 1976;16:442–451.

61. Rinehart BK, Terrone DA, Magann EF, etal. Preeclampsia-associated hepatic hem-orrhage and rupture: Mode of managementversus maternal-perinatal outcome. Am JObstet Gynecol. 1998;178:S119.

62. Greenstein D, Henderson J, Boyer T. Liverhemorrhage: Recurrent episodes duringpregnancy complicated by preeclampsia.Gastroenterology. 1994;106:1668–1671.

63. Sibai BM, Mabie BC, Harvey CJ, et al. Pul-monary edema in severe preeclampsia-eclampsia: Analysis of thirty-seven con-secutive cases. Am J Obstet Gynecol.1987;156:1174–1179.

64. Zlantnik MG. Pulmonary edema: Etiologyand treatment. Semin Perinatol. 1997;21:298–306.

65. Benedetti TJ, Kates R, Williams V. Hemo-dynamic observations in severe pre-eclampsia complicated by pulmonaryedema. Am J Obstet Gynecol. 1985;152:330–334.

66. Yeast JD, Halberstadt C, Meyer BA, et al.The risk of pulmonary edema and colloid

osmotic pressure changes during magne-sium sulfate infusion. Am J Obstet Gyne-col. 1993;169:1566–1571.

67. Oian P, Maltau JM, Noddeland H, et al.Transcapillary fluid balance in pre-eclampsia. Br J Obstet Gynaecol. 1986;93:235–239.

68. American College of Obstetricians andGynecologists. Invasive HemodynamicMonitoring in Obstetrics and Gynecology.ACOG Technical Bulletin No. 175, 1992.

69. Gilbert EM, Port JD. Deactivation of thesympathetic nervous system in patientswith chronic congestive heart failure. CurrCardiol Rep. 2000;2:225–232.

70. Naqvi R, Akhtar F, Ahmed E, et al. Acuterenal failure of obstetrical origin during1994 at one center. Renal Fail. 1996;18:681–683.

71. Lindheimer MD, Katz AI. Acute renal fail-ure. In: Gleicher N, Buttino L, Elkayam U,et al, eds. Principles and Practice of Medi-cal Therapy in Pregnancy, 3d ed. Stam-ford, CT: Appleton & Lange, 1998:1066.

72. Sibai BM, Villar MA, Mabie BC. Acute re-nal failure in hypertensive disorders ofpregnancy: Pregnancy outcome and re-mote prognosis in thirty-one consecutivecases. Am J Obstet Gynecol. 1990;162:777–783.

73. Rodriquez GD, Godina GM, HernandezCA, et al. Severe pre-eclampsia, HELLPsyndrome and renal failure. Ginecol ObstetMex. 1998;66:48–51.

74. Stratta P, Canavese C, Colla L, et al. Acuterenal failure in preeclampsia-eclampsia.Gynecol Obstet Invest. 1987;24:225–231.

75. Sibai BM, Ramadan MK. Acute renal fail-ure in pregnancies complicated by hemo-lysis, elevated liver enzymes, and lowplatelets. Am J Obstet Gynecol. 1993;168:1682–1687.

76. Kramer WB, Weiner CP. Disorders of he-mostasis. In: Cohen WR, ed. Cherry andMarkatz’s Complications of Pregnancy,5th ed. Baltimore: Lippincott Williams &Wilkins, 2000:346.

77. Sibai BM, Taslimi MM, el-Nazer A, et al.Maternal-perinatal outcome associatedwith the syndrome of hemolysis, elevatedliver enzymes, and low platelets in severepreeclampsia-eclampsia. Am J Obstet Gy-necol. 1986;155:501–509.


78. Roberts JM, May WJ. Consumptive coagu-lopathy in severe preeclampsia. Obstet Gy-necol. 1976;48:163–166.

79. Metz J, Cincotta R, Francis M, et al.Screening for consumptive coagulopathyin preeclampsia. Int J Gynaecol Obstet.1994;46:3–9.

80. Yuen TS, Kua IS, Tan IK. Spinal haema-toma following epidural anaesthesia in apatient with eclampsia. Anaesthesia. 1999;54:350–354.

81. Howie PW, Prentice CRM, Forbe CD.Failure of therapy to affect the clinicalcourse of severe preeclampsia. Br J ObstetGynaecol. 1975;82:711–717.

82. American College of Obstetricians andGynecologis ts . Blood ComponentTherapy. ACOG Technical Bulletin No.199. Washington, DC: ACOG, 1994.

83. Urato AC, Repke JT. May-Hegglin anom-aly: A case of vaginal delivery when bothmother and fetus are affected. Am J ObstetGynecol. 1998;179:260–261.

84. Mackay AP, Berg CJ, Atrash HK.Pregnancy-related mortality from pre-eclampsia and eclampsia. Obstet Gynecol2001;97:533–538.

85. Barton JR, Sibai BM. Acute life-threatening emergencies in preeclampsia-eclampsia. Clin Obstet Gynecol. 1992;35:402–413.

86. Repke JT. Preeclampsia and hypertension.In: Repke JT, ed. Intrapartum Obstetrics.New York: Churchill Livingstone,1996:271.

87. Prisant LM, Carr AA, Hawkins DW. Treat-ing hypertensive emergencies: Controlledreduction of blood pressure and protectionof target organs. Postgrad Med. 1993;93:92.

88. Jaffe G, Schatz H. Ocular manifestations ofpreeclampsia. Am J Ophthalmol. 1987;103:309–315.

89. Kesler A, Kaneti H, Kidron D. Transientcortical blindness in preeclampsia with in-dication of generalized vascular endotheli-al damage. J Neuro Ophthalmol. 1998;18:163–165.

90. Crosby ET, Preston R. Obstetrical anaes-thesia for a parturient with preeclampsia,HELLP syndrome and acute cortical blind-ness. Can J Anesth. 1998;45:452–459.

91. Cunningham FG, Fernandez CO, Hernan-

dez C. Blindness associated with pre-eclampsia and eclampsia. Am J Obstet Gy-necol. 1994;172:1291–1298.

92. Strandgaard S, Paulson OB. Cerebral auto-regulation. Stroke. 1984;15:413–416.

93. Chester EM, Agamanolis DP, Banker BQ,et al. Hypertensive encephalopathy: Aclinicopathologic study of 20 cases. Neu-rology. 1977;28:928–939.

94. Gifford RW. Management of hypertensivecrisis. JAMA. 1991;266:829–835.

95. Calhoun DA, Oparil S. Treatment of hy-pertensive crisis. N Engl J Med. 1990;323:1177–1183.

96. Schwartz RB, Jones KM, Kalina P, et al.Hypertensive encephalopathy: Findings onCT, MR imaging, and SPECT imaging in14 cases. Am J Radiol. 1992;159:379–383.

97. Cerebral lesions. In: Sheehan HL, LynchJB, eds. Pathology of Toxaemia of Preg-nancy. Baltimore: Williams & Wilkins,1973:524–553.

98. Saunders TG, Clayman DA, Sanchez-Ramos L, et al. Brain in preeclampsia: MRimaging with clinical correlation. Radiol-ogy. 1991;180:475–478.

99. Aguglia U, Tinuper P, Farnarier G, et al.Electroencephalographic and anatomico-clinical evidences of posterior cerebraldamage in hypertensive encephalopathy.Clin EEG. 1984;15:53–60.

100. Beausang-Linder M, Bill A. Cerebral cir-culation in acute arterial hypertension:Protective effects of sympathetic nervousactivity. Acta Physiol Scand. 1981;111:193–199.

101. Edvinsson L, Owman S, Sjoberg N-O. Au-tonomic nerves, mast cells, and amine re-ceptors in human brain vessels: Histo-chemical and pharmacologic study. BrainRes. 1976;115:377–393.

102. Trommer BL, Homer D, Mikhael MA. Ce-rebral vasospasm and eclampsia. Stroke.1988;19:326–329.

103. Coughlin WF, McMurdo SK, Reeves T.MR imaging of postpartum cortical blind-ness. J Comput Assist Tomogr. 1989;13:572–576.

104. Naidu K, Moodley J, Corr P, et al. Singlephoton emission and cerebral computer-ised tomographic scan and transcranialDoppler sonographic findings in eclamp-

328 NORWITZ ET AL

sia. Br J Obstet Gynaecol. 1997;104:1165–1172.

105. Torres P, Antolin E, Gratacos E, et al. Cor-tical blindness in preeclampsia: Diagnosticevaluation by transcranial Doppler andmagnetic resonance imaging techniques.Acta Obstet Gynecol Scand. 1995;74:642–644.

106. Apollon KM, Robinson JN, Schwartz RB,

et al. Cortical blindness in severe pre-eclampsia: Computed tomography, mag-netic resonance imaging and single-photonemission computed tomography findings.Obstet Gynecol. 2000;95:1017–1019.

107. Nag S, Robertson DM, Dinsdale HB. Ce-rebral cortical changes in acute hyperten-sion: An ultrastructural study. Lab Invest.1977;39:150–161.


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