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mniotic fluid embolism: an evidence-based review
gustín Conde-Agudelo, MD, MPH; Roberto Romero, MD
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mniotic fluid embolism (AFE) is arare and often fatal obstetric condi-

ion, characterized by sudden cardiovas-ular collapse, altered mental status, andisseminated intravascular coagulationDIC). The presence of fetal debris in theulmonary blood vessels of a motherho had died suddenly in labor was firstescribed by Meyer1 in 1926, but it wasot until 1941 that death following sud-en collapse during labor or in the im-ediate postpartum period was attrib-

ted to AFE.2

Understanding of the pathogenesis ofFE has increased in the last 2 decades

ince this disorder was recognized as 1 ofhe main causes of maternal mortality inhe United States.3 Evidence on AFE,owever, has been mainly based on indi-idual case reports, autopsy series, or un-ontrolled case series, due to the lowrequency of the condition. Moreover,everal aspects of this condition remain aubject of controversy. This review criti-ally examines, from the best availablevidence, the current knowledge regard-ng the epidemiology, pathogenesis,

rom the Perinatology Research Branch,unice Kennedy Shriver National Institute ofhild Health and Human Development/ational Institutes of Health/Department ofealth and Human Services, Bethesda, MD,

nd Detroit, MI (Drs Conde-Agudelo andomero); and the Center for Molecularedicine and Genetics, Wayne Stateniversity, Detroit, MI (Dr Romero).

eceived Dec. 17, 2008; revised April 10,009; accepted April 23, 2009.

eprints not available from the authors.

his study was supported by the Intramuralesearch Program of the Eunice Kennedyhriver National Institute of Child Health anduman Development, National Institutes ofealth, Department of Health and Humanervices.

002-9378/$36.002009 Published by Mosby, Inc.

ooi: 10.1016/j.ajog.2009.04.052

athophysiology, diagnosis, and treat-ent of AFE.

aterials and methodse searched several databases (all from

nception to March 31, 2009) with theerms “amniotic embolism” and “amni-tic embolus.” We also searched refer-nces in retrieved articles, book chapters,eview articles, and reports on maternalortality from surveillance systems. In-

lusion of individual articles was basedn scientific merit and clinical relevance.he great majority of studies includedere descriptive, mainly case reports and

ase series. We also included 2 popula-ion-based cohort studies and 6 case-ontrol studies. Methodological qualityas assessed using guidelines proposed

or improving the reporting of thesetudies.4,5 Details of methods used in theeview are presented in the Appendix.

esultsncidencen 1941, Steiner and Lushbaugh,2 basedn the occurrence of 3 cases of fatal AFE

n the first 24,200 deliveries at the Newhicago Lying-In Hospital, estimated

he incidence of AFE to be about 1 in000 deliveries (maternal mortality ratio

We conducted an evidence-based review(AFE). The estimated incidence of AFE isAmerica and Europe, respectively. The casewith AFE are 13-30% and 9-44%, respectivrisk of AFE include advanced maternal ageeclampsia, polyhydramnios, cervical laceraresponse in AFE is biphasic, with initial pfailure, followed by left ventricular failure. Prvasodilators and recombinant activated factpresented.

Key words: amniotic fluid embolism, cardiointravascular coagulation, maternal death, mperinatal mortality, pregnancy

Cite this article as: Conde-Agudelo A, Romero R.Am J Obstet Gynecol 2009;201:445.e1-13.

f 12.4 deaths per 100,000 deliveries), O

NOVEMBER 2009 Americ

ut they subsequently realized that thisas an overestimation, since no more

ases were observed in the next 26,000eliveries (corrected maternal mortalityatio of 6.0 deaths per 100,000 deliver-es).6 Forty studies2,6-44 had data on thencidence of AFE and/or associated mater-al and perinatal mortality around theorld. Details of these studies are pro-ided in the supplementary appendixavailable online at www.ajog.org). Ac-ording to recent large population-basedtudies,24,36,38,40,42,43 the incidence ofFE, which includes both fatal andonfatal cases, ranges between 1 in2,953 deliveries in the United States,40

o 1 in 56,500 in the United Kingdom.43

ased on those studies, the pooled esti-ated incidence of AFE would be 1 in

5,200 deliveries (95% confidence intervalCI], 1 in 13,900 to 1 in 16,700 deliveries)n North America24,36,40 and 1 in 53,800eliveries (95% CI, 1 in 48,800 to 1 in9,900 deliveries) in Europe.38,42,43 Thereere no available data on incidence of AFE

n other regions of the world. The true in-idence of AFE, however, is difficult toetermine because the diagnosis of thisyndrome remains one of exclusion, withossible underreporting of nonfatal cases.

nformation about amniotic fluid embolism5,200 and 1:53,800 deliveries in North

ality rate and perinatal mortality associated. Risk factors associated with an increasedcental abnormalities, operative deliveries,s, and uterine rupture. The hemodynamiconary hypertension and right ventricular

ising therapies include selective pulmonaryIIa. Important topics for future research are

scular collapse, DIC, disseminatedernal morbidity, maternal mortality,

iotic fluid embolism: an evidence-based review.

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4

verdiagnosed for medicolegal reasons,ince this complication is widely consid-red to be an unavoidable cause of mater-al death. Additional research will beeeded to evaluate why the incidence ofFE is over 3 times higher in North Amer-

ca than in Europe.

aternal and perinatal mortalityhe maternal mortality ratio associatedith AFE ranged between 0.5-1.7 deaths

TABLE 1Risk factors for amniotic fluid embin large population-based cohort s

Characteristic

Maternal age �20 years...................................................................................................................

Maternal age �35 years...................................................................................................................

Elderly primigravidity...................................................................................................................

Grand multiparity...................................................................................................................

Black race...................................................................................................................

Other minority ethnic groups...................................................................................................................

Previous cesarean section...................................................................................................................

Medical induction of labor...................................................................................................................

Induction of labor...................................................................................................................

Cesarean delivery

...................................................................................................................

Forceps delivery...................................................................................................................

Vacuum delivery...................................................................................................................

Multiple pregnancy...................................................................................................................

Placenta previa...................................................................................................................

Abruptio placenta...................................................................................................................

Placenta previa or abruptio placenta...................................................................................................................

Preeclampsia...................................................................................................................

Eclampsia...................................................................................................................

Diabetes...................................................................................................................

Premature rupture of membranes...................................................................................................................

Chorioamnionitis...................................................................................................................

Fetal distress...................................................................................................................

Dystocia...................................................................................................................

Polyhydramnios...................................................................................................................

Fetal macrosomia...................................................................................................................

Cervical laceration or uterine rupture...................................................................................................................a For cephalic presentation; b For noncephalic presentation.

Conde-Agudelo. AFE: an evidence-based review. Am J Ob

er 100,000 live births or deliveries (0.5 l

45.e2 American Journal of Obstetrics & Gynecolo

or Sweden and the United Kingdom, 0.7or Canada, 1.5 for Australia, and 1.0-1.7or the United States). In developingountries, the reported maternal mortal-ty ratios ranged between 1.8-5.9 per00,000 deliveries. Overall, in the last 10ears, AFE accounted for 5.0-15.0% of allaternal deaths in developed countries

5.3% for the United Kingdom, 10.9%or Canada, 13.1% for Australia, and3.7% for the United States), being the

smiesdjusted odds ratio (95%onfidence interval)

ramer et al36 Abenhaim et al40

0.2 (0.1–0.96) 0.4 (0.2–0.9)..................................................................................................................

1.9 (1.4–2.7) 2.2 (1.5–2.1)..................................................................................................................

0.6 (0.2–1.9) 1.0 (0.3–3.3)..................................................................................................................

1.8 (0.3–13.0) —..................................................................................................................

2.4 (1.5–3.6)..................................................................................................................

2.3 (1.5–3.6)..................................................................................................................

0.8 (0.5–1.2) 0.9 (0.6–1.3)..................................................................................................................

1.8 (1.3–2.7) —..................................................................................................................

1.5 (0.9–2.3)..................................................................................................................

2.5 (7.9–19.9)a

8.6 (4.3–17.4)b5.7 (3.7–8.7)

..................................................................................................................

5.9 (3.4–10.3) 4.3 (1.9–6.6)..................................................................................................................

2.9 (1.6–5.3) 1.9 (1.0–3.7)..................................................................................................................

2.5 (0.9–6.2) 1.5 (0.6–4.1)..................................................................................................................

30.4 (15.4–60.1)..................................................................................................................

8.0 (4.0–15.9)..................................................................................................................

3.5 (2.3–5.5) —..................................................................................................................

1.4 (0.8–2.5) 7.3 (4.3–12.5)..................................................................................................................

1.5 (2.8–46.9) 29.1 (7.1–119.3)..................................................................................................................

1.5 (0.6–3.8) 2.3 (0.6–9.2)..................................................................................................................

1.1 (0.6–2.0) 0.7 (0.4–1.5)..................................................................................................................

1.4 (0.6–3.2) 1.6 (0.7–3.4)..................................................................................................................

1.7 (1.2–2.5) 1.5 (1.0–2.2)..................................................................................................................

0.6 (0.4–0.8) 0.4 (0.2–0.7)..................................................................................................................

3.0 (1.2–7.3) —..................................................................................................................

1.6 (0.9–3.0) —..................................................................................................................

3.8 (1.2–12.0) —..................................................................................................................

Gynecol 2009.

eading cause of maternal death in Aus- d

gy NOVEMBER 2009

ralia, the second cause of maternaleath in the United States, the thirdause of maternal death in France andoland, and the second leading cause ofirect maternal death in the Unitedingdom. In China, regional studies re-orted that AFE was the second cause ofaternal death.In 1979, Morgan,11 based on 272 cases

f AFE published in the English litera-ure, reported a maternal fatality rate of6%. In Clark et al’s national registry, theaternal fatality rate was 61% for the pe-

iod 1988-1994.19 More recent popula-ion-based studies have reported a de-rease in case fatality rate from AFE13.3% for Canada, 21.6% for the Unitedtates, 24.0% for the United Kingdom,nd 44.0% for Sweden), justifying theiew that this condition should not beonsidered uniformly lethal. This coulde due to improved reporting, inconsis-ent case definitions, or improvements inreatment. Another possibility is publi-ation bias in previous series, due to se-ective reporting of severe cases. Theerinatal mortality associated with fatalFE in the last decade ranged between 9nd 44%.37,39

isk factorsntil recently, the understanding of the

isk factors for the development of AFEerived from case reports, autopsy series,r cumulative reviews in which there waso control group for comparisons. As ofarly 2009, only 2 large population-ased retrospective cohort studies,36,40

ach using data from 3 million hospitaleliveries, have examined the independ-nt association between AFE and severalotential risk factors after controlling forhe effects of confounders (Table 1). Riskactors found in both studies to be signif-cantly associated with an increased riskf AFE included maternal age of 35 yearsr older, cesarean delivery, forceps-as-isted and vacuum-assisted vaginal de-iveries, placenta previa, abruption pla-enta, eclampsia, and fetal distress.nfortunately, the ability to make infer-

nces about causality is limited, becauseemporal relationships cannot be deter-

ined when using these databases. Thus,lthough operative deliveries and fetal

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le that reverse causality explains thesessociations. Other significant risk fac-ors associated with AFE were polyhy-ramnios and a cervical laceration orterine rupture in the Canadian study36

nd African American race and otherinority ethnic groups in the American

tudy.40 With regard to induction of la-or, the 2 studies yielded conflicting re-ults: the Canadian study36 reported that

edical induction of labor nearly dou-led the risk of AFE compared withpontaneous labor (adjusted odds ratioOR], 1.8; 95% CI, 1.3–2.7), whereas themerican study40 did not find a signifi-ant association (adjusted OR, 1.5; 95%I, 0.9 –2.3). Preeclampsia was found toe a significant risk factor for AFE in themerican study but not in the Canadian

tudy. Maternal age below 20 years andystocia were significant protective fac-ors against the development of AFE inoth studies. Advanced maternal age inhe first pregnancy, primigravidity, higharity, previous cesarean section, diabe-es, multiple gestations, premature rup-ure of membranes, chorioamnionitis,nd fetal macrosomia did not alter theisk of AFE.

The results of these studies, however,ould have been influenced by the facthat identification of AFE was based onhe clinical diagnosis as recorded in the

edical record, without other verifyingvidence, and depended on correct cod-ng of that diagnosis. Moreover, nonfatalFE might have been overdiagnosed in

hese studies. A prospective, nationaltudy of amniotic fluid embolism usinghe UK Obstetric Surveillance SystemUKOSS) is currently in the process ofssessing whether these risk factors areresent in this population.43

athogenesishe pathogenesis of AFE is poorly un-erstood. The entrance, by various pro-osed mechanisms and routes, of amni-tic fluid into the systemic maternalirculation, which then triggers clinicalanifestations of the condition, contin-

es to be the principal mechanism in-oked in the pathogenesis of AFE. Tradi-ionally, it has been assumed that inrder for AFE to occur there must be a
reach in the physical barriers between H
he maternal and fetal compartments,ainly at the level of endocervical

eins,45,46 uterine trauma sites,47 and thelacental attachment site.47 A pressureradient that favors the entry of amnioticuid from the uterus into the maternalirculation is thought to be present.48

upport for this hypothesis comes fromhe work of Talbert et al,49 who foundhat significant amounts of 125I-labeledlbumin were transferred from amnioticuid into the maternal circulation fol-

owing intraamniotic injection of hyper-onic saline. This mechanism probablyxplains the increased risk of AFE amongomen with placenta previa, placental

bruption, operative deliveries, cervicalacerations or uterine rupture, and poly-ydramnios. With regard to the mecha-ism for the “late presentation” of AFE,ourtney50 proposed that amniotic fluidnd fetal debris trapped in the uterineeins at the time of delivery may be re-eased into the circulation later duringterine involution.The traditional view has been that

ntry of amniotic fluid into the mater-al circulation results in obstruction ofulmonary capillaries by amnioticuid emboli, leading to cardiovascularollapse. However, the usual absencef physical evidence of pulmonary ves-el obstruction, the high degree in vari-bility in clinical course, and the fail-re to consistently reproduce theisease in animal models51,52 suggesthat physical obstruction to the circu-ation is not the main mechanism ofFE. Some investigators have sug-ested that immunologic factors coulde involved in the pathogenesis of thisyndrome.53-56 In 1984, Hammer-chmidt et al53 found that amnioticuid could activate complement when

ncubated with normal plasma andostulated that complement and gran-locyte activation by amniotic fluidould contribute to the pulmonary col-apse in this syndrome. In 1993, Ben-on55 suggested that AFE might resultrom anaphylaxis to fetal material leak-ng into the maternal circulation,hich would stimulate a cascade of en-ogenous-immune mediators, result-

ng in a reaction similar to anaphylaxis.
owever, in a further study, this same t

nvestigator did not find evidence toupport the role of mast cell degranu-ation (anaphylaxis) in the pathophys-ology of the disease.57 In contrast, allf the 8 women with AFE had abnor-ally low C3 and C4 complement con-

entrations, suggesting that comple-ent activation could play a role in the

athogenesis of AFE. This hypothesisemains to be proved.56

athophysiologyhe entrance into the circulation of am-iotic fluid constituents could result in

he release of various primary or second-ry endogenous mediators, which causehe principal physiologic derangementshat characterize this syndrome. The listf proposed mediators is extensive and

ncludes histamine,56 bradykinin,58 en-othelin,59,60 leukotrienes,61 and otherrachidonic acid metabolites.62

emodynamic changeshe initial explanations for the hemody-amic changes associated with AFE wereased on findings from animal experi-entation.63,64 In general, experimentalFE produced severe pulmonary arteryypertension, leading to acute cor pul-onale without evidence of left ventric-

lar compromise.65 This was attributedo a vasoconstrictor response of the pul-

onary vasculature to the presence ofmniotic fluid or particulate matter inmniotic fluid.11 In 1985, Clark et al66

hallenged this traditional view. Reana-yzing 5 published cases of AFE, whichncluded hemodynamic data derived fromulmonary artery catheterization, as wells a report of a sixth case, these authorseported only mild to moderate in-reases in mean pulmonary artery pres-ure, a variable increase in central venousressure, and a high pulmonary capillaryedge pressure with evidence of left ven-

ricular failure. These findings were con-rmed 3 years later by the same group67

n 4 women suffering from AFE, with he-odynamic data derived from pulmo-

ary artery catheterization performedithin 2 hours of the acute cardiovascu-

ar collapse. In 1999, Shechtman et al68

ublished the first report of transesoph-geal echocardiography findings during
he hyperacute stage of AFE (within 30

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inutes of the collapse). Transesopha-eal 4-chamber images showed severeulmonary hypertension, acute rightentricular failure with a leftward devia-ion of the interatrial and interventriculareptum, and severe tricuspid regurgita-ion. There were no signs of left ventricularysfunction or of pulmonary edema. Sim-

lar findings were subsequently reportedn 4 cases in which transesophageal echo-ardiography was performed during thearly course of AFE.69-72 In all of theseases, transesophageal echocardiogra-hy showed that left ventricular failureas secondary to impaired left ventricu-

ar filling, because of a dilated right ven-ricle with deviation of the interventric-lar septum. These findings suggest thatulmonary vasoconstriction and in-reased pulmonary vascular resistancere the primary mechanisms responsibleor the cardiovascular collapse in AFE. Its important to highlight that most stud-es demonstrating left ventricular failures the main hemodynamic alteration as-ociated with AFE were performed morehan 1 hour after the onset of clinicaligns. In conclusion, the current avail-ble evidence suggests that the hemody-amic response to AFE is biphasic, withn initial increase in pulmonary vascularesistance and right ventricular failure,ollowed by left ventricular failure.54 Ad-itional explanations for the left ventricu-

ar failure include ischemic injury to theyocardium66 and/or a possible directyocardial depressant effect of amniotic

uid or other mediators.54 Hypoxemiaould be explained by the severe ventila-ion-perfusion mismatching due to in-ense vasoconstriction of the pulmonaryasculature that occurs during the initialhase.

oagulopathylthough the precise mechanism induc-

ng DIC from AFE remains unclear, it isrobably multifactorial. In vitro, amni-tic fluid decreases whole blood clottingime, produces a “thromboplastin-likeffect,” induces platelet aggregation andctivates the complement cascade.73 Theurrent hypothesis is that, in AFE, theresence of tissue factor in amnioticuid activates the extrinsic pathway by
inding with factor VII, and this triggers K

lotting by activating factor X, with theubsequent development of a consump-ive coagulopathy.74-76 The activation ofhe clotting cascade in the pulmonaryasculature may cause generation of mi-rovascular thrombosis, which couldhen cause vasoconstriction.74 Addi-ional data report that high levels of a la-ent form of plasminogen activator in-ibitor type 1 in amniotic fluid can beeactivated by a denaturing agent in theaternal circulation, leading to DIC.77

ecently, it has been proposed that DICay be a secondary result of comple-ent activation rather than the direct in-

roduction of procoagulants into theaternal circulation.56

There is controversy about the extent tohich bleeding is due to a consumption

oagulopathy or to massive fibrinolysis.arnett et al,78 using thromboelastogra-

hy analysis, have demonstrated that theddition of amniotic fluid to blood fromregnant women causes a hypercoagulabletate related to the procoagulant activity ofmniotic fluid and enhanced platelet acti-ation, but there was no evidence of fibri-olysis, suggesting that the primary causef bleeding in AFE is consumption coagu-

opathy. Similar results were reported byiu et al,79 using blood from nonpregnantomen.

istopathologyhe gross pathologic changes are usuallyonspecific and can include pulmonarydema, atelectasis, pulmonary conges-ion, emphysema, and evidence ofhrombosis. Usually, there are no visiblehrombi in the main pulmonary arteries,eart, or elsewhere.2,80 The traditionaliew was that the diagnosis could beased on demonstrating the presence ofetal debris, presumably from the amni-tic fluid, within the pulmonary vascu-

ature. Amniotic fluid contains epithelialquamous cells from the fetal skin, mu-in derived from meconium excreted byhe fetal intestine, fat derived from theernix caseosa, and hair.2,78 These con-tituents can be specifically identified bysing immunohistochemical markers

or cytokeratin AE1/AE3, Alcian blue orucicarmine staining, oil red O staining,

nd polarized light, respectively.81-83

obayashi et al84 reported that immuno- b

gy NOVEMBER 2009

istochemical staining using the mono-lonal antibody TKH-2 is a more sensi-ive method to detect meconium andmniotic fluid-derived mucin in the lungections of patients with AFE than con-entional hematoxylin eosin or Alcianlue staining. Oi et al85 reported positiveKH-2 staining within the pulmonaryasculature in 14 of 15 (93%) womenith AFE. Recently, Fineschi et al86 eval-ated complement C3a expression as aistopathological test for diagnosing fa-al AFE. In all of the 8 women who diedf AFE, the expression of complement3a was lower than in the control group

6 women dying of trauma during preg-ancy). Fetal debris has also been de-

ected in the capillaries of the cervix,ower uterine segment, kidneys, heart,iver, spleen, adrenal glands, pancreas,nd brain.2,45,46,80,87-89 The current view,owever, is that amniotic fluid embolism

s a clinical syndrome, and that the diag-osis depends on the clinical presenta-

ion, rather than on histopathologicxamination.

linical manifestationsFE typically occurs during labor andelivery or in the immediate postpar-um period, although it can occur asate as 48 hours postpartum. About0% of cases occur before deliveryrange, 63–76%).13,19,25,35,40 AFE haslso been reported to occur followingnduced abortion,90,91 feticide,92,93 in-rapartum amnioinfusion,94,95 trans-bdominal amniocentesis,96,97 bluntbdominal trauma,98,99 surgical trau-a,100 removal of a cervical suture,101

nd manual removal of placenta.102

he classic presentation of AFE is char-cterized by sudden cardiovascularollapse, with profound systemic hy-otension, cardiac dysrhythmia, cya-osis, dyspnea or respiratory arrest,ulmonary edema or the adult respira-ory distress syndrome, altered mentaltatus, and hemorrhage. These signsnd symptoms of AFE can occur sepa-ately or in combination and in differ-nt degrees. The precise progression ofigns and symptoms in the initial phasef AFE has been difficult to elucidate,
ecause of the low frequency of the

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Frequencies of the main presentingigns and symptoms of AFE reported inarge case series are summarized in theupplementary appendix available on-ine. It should be emphasized that thisnformation could be affected by under-eporting of signs and symptoms in clin-cal records. The most common present-ng signs and symptoms includedypotension, respiratory distress, andyanosis, which were detected in up to00% of women, DIC in approximately0% (range, 22– 83%), and seizures inbout 20% (range, 10 – 48%). The per-entage of patients experiencing cardiacrrest and dyspnea varied between 30-7% and 48-72%, respectively. Fetal dis-ress was diagnosed in 50-100% of cases.ases of AFE with atypical presentations,

n which coagulopathy43,103-105 or severeetal bradycardia106,107 are the initial orven the only presenting feature haveeen reported in the literature. Maternaleath due to AFE is typically caused byudden cardiac arrest, hemorrhage fromoagulopathy, or the development ofcute respiratory distress syndromend/or multisystem organ failure afternitial survival of the acute event.

remonitory symptomshe seventh report of the confidentialnquiry into maternal deaths in thenited Kingdom39 highlighted that 11 of

7 women who suffered AFE reportedome or all of the following symptoms:reathlessness, chest pain, feeling cold,

ightheadedness, distress, panic, a feelingf pins and needles in the fingers, nausea,nd vomiting. The interval between thenset of these symptoms and the collapsearied (from almost immediately to overhours later). These symptoms might

ndicate hypoxia and might give therst clue to the diagnosis of amnioticuid embolism in progress before col-

apse and hemorrhage occur. Tuffnell35

uggested that monitoring maternal ox-genation by pulse oximetry in these cir-umstances could be considered in theeripartum period to detect at an early
tage women who may develop AFE. s
iagnosishe diagnosis of AFE is based on thelinical presentation and is essentiallyne of exclusion. Although wide consen-us based on objective criteria is still to bechieved, the diagnosis is suspected in aoman experiencing several of the fol-

owing features: hypotension (and/orardiac arrest), respiratory distress, DIC,r coma and/or seizures during preg-ancy or within 48 hours of delivery, in

he absence of other medical conditionr potential explanation for the symptomsnd signs observed.56 Since some womenith AFE may have secondary condi-

ions, the emphasis is on whether thesether medical problems seem to be theost likely cause of the women’s illness.Laboratory tests are nonspecific (a

omplete blood count, coagulation pro-le, arterial blood gases, cardiac en-ymes, and electrolytes). The whitelood cell count may be elevated and, de-ending on the presence of DIC, the he-oglobin and hematocrit values will be

ow. The laboratory manifestations ofIC include prolonged prothrombin

nd partial thromboplastin times, withecreased fibrinogen levels. Thrombo-ytopenia is a rare finding. Cardiac en-ymes may be elevated, and arteriallood gases may show hypoxemia. Thelectrocardiogram may show tachycar-ia, with a right ventricular strain pat-ern in the early stage and ST and T wavebnormalities. Cardiac arrhythmias orsystole can be seen with severe cardio-ascular collapse. Pulse oximetry may re-eal a sudden drop in oxygen saturation.he chief radiographic abnormalities inFE are diffuse bilateral heterogeneousnd homogeneous areas of increasedpacity, which are indistinguishablerom acute pulmonary edema fromther causes.108 Transesophageal echo-ardiography may demonstrate severeulmonary hypertension, acute rightentricular failure with a leftward devia-ion of the interatrial and interventricu-ar septum, and a cavity-obliterated leftentricle during the early phase ofFE.68-72 Occasionally, transient intra-ardiac thrombi109 or embolus110 can be
een. p

No specific laboratory tests are avail-ble for making a diagnosis of AFE, yeteveral tests have been proposed to in-rease the index of suspicion for this di-gnosis (Table 2). In 1976, Resnik et al111

rst reported the identification of amni-tic fluid debris in central venous bloodspirated from the distal lumen of a pul-onary arterial catheter of a survivoroman with AFE. This finding has been

eported several times.112-115 However,n Clark et al’s national registry19 only 4f 8 women (50%) had this finding. Inddition, the detection of squamous cellsn the pulmonary arterial circulation isot pathognomonic for AFE, since theyave been identified in 21-100% of preg-ant women without AFE116-119 and inonpregnant women.118,120 Unfortu-ately, reliable differentiation betweenaternal and fetal squamous cells is still

ifficult in the clinical setting. Thus, theetection of squamous cells in the mater-al pulmonary arterial circulation is notufficient for the diagnosis of AFE. Thedentification of such findings in the ma-ernal pulmonary arterial circulation isupportive of the diagnosis when theyre found in large numbers, are coatedith neutrophils, and/or they are accom-anied by other fetal debris.115,119

Diagnostic markers for AFE based oneripheral blood analysis have also beenuggested. These include zinc copropor-hyrin, sialyl Tn antigen, tryptase, andomplement factors. Kanayama et al121

ound that plasma concentrations of zincoproporphyrin (a characteristic com-onent of meconium) were increased inll of the 4 women with AFE but in only 1f 50 control cases without the diagnosisf AFE. Three studies57,85,122 have evalu-ted the diagnostic accuracy of serumialyl Tn, a fetal antigen present in meco-ium and amniotic fluid, detected

hrough the use of the TKH-2 monoclo-al antibody. Serum concentrationsreater than 50 U/mL yielded sensitivi-ies between 78-100% and the specifici-ies between 97-99%. Increased serumevels of tryptase, a marker of mast cellegranulation, in women with AFE haveeen reported by some authors123,124 butot by others.83,125 Benson et al57 re-
orted that serum tryptase was negative

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n all of the 6 women with AFE. How-ver, they found that decreased serumevels of C3 and C4 complement hadensitivities between 88-100% and apecificity of 100% for the diagnosis ofFE. It should be noted that all of these

aboratory tests are not currently avail-ble in the majority of hospitals. In con-lusion, at the present time there is noest that can reliably confirm the diagno-is of AFE in suspected cases. Serum di-gnostic markers, such as zinc copropor-hyrin, sialyl Tn antigen, and C3 and C4omplement, are promising, but furthertudies are needed.

ifferential diagnosiseveral obstetric and nonobstetric life-hreatening emergencies may presentith a clinical picture similar to AFE.he differential diagnosis of AFE is ex-

ensive and includes disorders of em-olic, cardiac, respiratory, infectious,

TABLE 2Performance of tests proposed for

Author, year Test

DiMarzo,116 1984 Squamous cells incentral venousblood

...................................................................................................................

Kuhlman,117 1985 Squamous cells incentral venousblood

...................................................................................................................

Clark,118 1986 Squamous cells inpulmonary arterialblood

...................................................................................................................

Lee,119 1986 Squamous cells inpulmonary arterialblood

...................................................................................................................

Clark,19 1995 Amniotic fluiddebris in pulmonaryarterial blood

...................................................................................................................

Kanayama,121 1992 Zinc coproporphyrin...................................................................................................................

Kobayashi,122 1993 Sialyl Tn antigen...................................................................................................................

Oi,85 1998 Sialyl Tn antigen...................................................................................................................

Benson,57 2001 Sialyl Tn antigen....................................................

Serum tryptase

....................................................

C3 complement....................................................

C4 complement...................................................................................................................

AFE, amniotic fluid embolism; NR, not reported.

Conde-Agudelo. AFE: an evidence-based review. Am J Ob

nd immunologic nature (Table 3). s


reatmenthe management of AFE is supportivend directed toward the maintenance ofxygenation, cardiac output and bloodressure, and correction of the coagu-

opathy. Treatment should take place inn intensive care unit, if possible. In thevent of maternal cardiac arrest, cardio-ulmonary resuscitation should be initi-ted immediately and, if the gestationalge of an undelivered alive fetus is viable,esarean section could be considered.126

terine evacuation after unsuccessful re-uscitation may be therapeutic for the

other, because the weight of the gravidterus on the inferior vena cava impedeslood return to the heart and decreasesystemic blood pressure.127,128

Monitoring of the patient with sus-ected AFE should include continuousardiac telemetry monitoring to detectnd treat arrhythmias, continuous re-

gnosing amniotic fluid embolism in

Abnormal test resultAFEcases, n No

Presence of squamous cells 0 11

.........................................................................................................................

Presence of squamous cells 1

.........................................................................................................................


.........................................................................................................................


.........................................................................................................................

Presence of amniotic fluiddebris

8

.........................................................................................................................

Serum levels �35 nmol/L 4 5.........................................................................................................................

Serum levels �50 U/mL 4 3.........................................................................................................................

Serum levels �50 U/mL 19 12.........................................................................................................................

Serum levels �50 U/mL 9 2.........................................................................................................................

Increased levels in serum;cutoff point NR

6 2

.........................................................................................................................

Serum levels �70 mg/dL 8 2.........................................................................................................................

Serum levels �16 mg/dL.........................................................................................................................

Gynecol 2009.

piratory monitoring with pulse oxim- d

gy NOVEMBER 2009

try or with an end-tidal CO2 monitor,ontinuous blood pressure monitor-ng, and pulmonary artery catheter for

onitoring cardiac output, central ve-ous pressure, pulmonary capillaryedge pressure, systemic vascular re-

istance, and pulmonary artery pres-ures.129,130 In addition, a pulmonaryrtery catheter guides hemodynamicanagement and provides direct ac-

ess to blood samples for monitoringf arterial gases. Transesophagealchocardiography has also been re-orted to be useful in evaluating car-iac function and guiding fluid ther-py. Initial laboratory data generallyncludes a complete blood count withlatelets; type and cross-matching; ar-erial blood gases; electrolytes; andoagulation studies, including pro-hrombin time, partial thromboplastinime, fibrin degradation products, D-

pected cases

FE cases, nSensitivity,%

Specificity,%

efore delivery)fter delivery)

— 90

..................................................................................................................

100 40

..................................................................................................................

100 0

..................................................................................................................

— 79

..................................................................................................................

50 —

..................................................................................................................

100 98..................................................................................................................

100 96..................................................................................................................

90 99..................................................................................................................

78 NR..................................................................................................................

0 NR

..................................................................................................................

88 100..................................................................................................................

100 100..................................................................................................................

dia sus

n-A

1 (b6 (a

......... .........

5

......... .........

5

......... .........

4

......... .........

0

......... .........

0......... .........

2......... .........

0......... .........

2......... .........

2

......... .........

2......... .........

......... .........

imer, and antithrombin III levels.

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The initial goal is the rapid correctionf maternal hemodynamic instability,hich includes correction of hypoxia

nd hypotension, for preventing addi-ional hypoxia and subsequent end-or-an failure. Oxygen can be administeredmmediately by whatever means neces-ary, including face mask, bag-valve

ask, or endotracheal intubation, inoncentrations adequate to keep oxygenaturation at 90% or higher.129,130 Treat-

ent of hypotension includes optimiza-ion of the preload, with rapid volumenfusion of isotonic crystalloid solutions.luid therapy should be based on pul-onary artery catheter or transesopha-

eal echocardiography monitoring. Inases of refractory hypotension, vaso-ressors such as dopamine or norepi-ephrine may be necessary. Inotropes,uch as dobutamine, dopamine, and

ilrinone, can be added, because �-ad-energic agonists improve myocardialontractility in addition to the �-adren-rgic vasoconstrictor effects. It is desir-ble to maintain systolic blood pressure

TABLE 3Differential diagnosis of amnioticfluid embolismPulmonary thromboembolism...........................................................................................................

Air embolism...........................................................................................................

Anesthetic complications (total spinalor high epidural block)...........................................................................................................

Drug-induced allergic anaphylaxis...........................................................................................................

Myocardial infarction...........................................................................................................

Cardiac arrhythmia...........................................................................................................

Peripartum cardiomyopathy...........................................................................................................

Aortic dissection...........................................................................................................

Aspiration of gastric contents...........................................................................................................

Reaction to local anesthetic drugs...........................................................................................................

Blood transfusion reaction...........................................................................................................

Sepsis...........................................................................................................

Postpartum hemorrhage...........................................................................................................

Uterine rupture...........................................................................................................

Placental abruption...........................................................................................................

Eclampsia...........................................................................................................

Conde-Agudelo. AFE: an evidence-based review.Am J Obstet Gynecol 2009.

t or higher than 90 mmHg, an arterial f

aO2 of at least 60 mmHg, with accept-ble organ perfusion, as indicated by arinary output of at least 0.5 mL/kg/h orreater than 25 mL/h.129,130

Administration of blood componentss considered the first line of treatmentor correcting the coagulopathy associ-ted with AFE. Since DIC is frequentlyssociated with severe hemorrhage,ransfusion of packed red blood cells is ariority in order to maintain oxygen de-

ivery to the tissues. Specific laboratoryoagulation abnormalities are treatedith transfusion of fresh frozen plasma,latelets, and/or cryoprecipitate. Cryo-recipitate is particularly useful, because

t can be administered to replenish clot-ing factors in lieu of fresh frozen plasma.n addition, since cryoprecipitate con-ains fibronectin, it could facilitate theemoval of cellular and particulate mat-er, such as amniotic fluid debris, fromhe blood via the monocyte/macrophageystem.46,131 Recently, recombinant acti-ated factor VIIa has been used to man-ge severe DIC resistant to conventionallood product replacement in womenith AFE.132,133 Uterine bleeding in aoman already delivered can be con-

rolled by massage and use of intrave-ous oxytocin. If uterine bleeding is un-esponsive to these methods, manualxploration to look for fragments of re-ained placenta or membranes or aearch for cervical or uterine lacerationseeds to be considered. If bleeding isrofuse and pharmacological interven-ion is unsuccessful, a hysterectomy maye necessary.Several other less common therapeu-

ic approaches have been reported anec-otally, including aprotinin134,135 anderine proteinase inhibitor FOY136 to

anage DIC, uterine artery embolizationor controlling severe postpartum hemor-hage,125,137 cardiopulmonary bypass forhe treatment of catastrophic pulmonaryasoconstriction,69 cardiopulmonary by-ass and pulmonary artery thromboem-olectomy,138 inhaled aerosolized prosta-yclin as a selective pulmonary vasodilatoror the treatment of severe hypoxemia,139

hrombolysis with tissue-plasminogen ac-ivator,140 continuous hemodiafiltrationor presumably eliminating amniotic fluid
rom the maternal blood stream, removal t

f cytokines, and treatment of metaboliccidosis,141 arteriovenous hemofiltra-ion,142 exchange transfusion,143 extracor-oreal membrane oxygenation and in-raaortic balloon counterpulsation forreating left ventricular failure unrespon-ive to medical therapy.144 The use of hep-rin therapy to treat DIC and corticoste-oids is controversial.

Recently, McDonnell et al72 reportedhe successful use of inhaled nitric oxide,selective pulmonary vasodilator, in the

reatment of acute right ventricular fail-re and pulmonary hypertension in aase of AFE presenting as cardiovascularollapse during labor. Other selectiveulmonary vasodilators that might beeneficial for the treatment of severe pul-onary hypertension of AFE include

rostacyclin and sildenafil.

rognosishe prognosis of a woman experiencingFE has improved with early diagnosisnd prompt and aggressive treatment by

multidisciplinary team.145 Althoughase fatality rates for AFE have fallen,here is still significant morbidity amongurvivors. In Clark et al’s national regis-ry,19 among the survivors, persistingeurological impairment was reported

n 61% of women and 50% of infants. Inhe United Kingdom registry,35 of the 31omen who survived, 6% had persistingeurological impairment, whereas of the3 infants who survived, 18% developedypoxic ischemic encephalopathy and% developed cerebral palsy.

ecurrencetotal of 9 cases of successful pregnancy

ollowing AFE, with no instances of re-urrent AFE, have been reported in theiterature.21,146-151 Therefore, althoughhe available information is limited, theurrent evidence suggests that AFE is notrecurrent disease.

omment and conclusionsith the exception of research on risk

actors and some diagnostic tests, thevailable literature on AFE is mainlyased on case reports or case series.hus, there is a need for future research

o generate information based on aigher level of evidence, and observa-
ional studies are needed. For reliable ev-

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4

dence on rare entities such as AFE, weeed systematic review of case reportsnd case series rather than a haphazardelection of them. Therefore, a world-ide registry of patients with this com-lication in which uniform diagnosticriteria be used is urgently needed to ad-ress comprehensively unanswereduestions. Clinicians should be encour-ged to report cases uniformly for facili-ating direct comparisons of individualeports and the performance of system-tic reviews.

Although the understanding of AFEas improved in the last decade, this en-ity continues to be associated with aigh rate of maternal and perinatal mor-idity and mortality. The possible asso-iation between AFE and both cesareanection and induction of labor deservesecular monitoring, given the increasingse of these interventions. More researchn promising serum diagnostic tests,uch as zinc coproporphyrin, sialyl Tnntigen, and C3 and C4 complement, iseeded. In addition, it is a priority to de-elop reliable histologic or immunologicethods to differentiate adult from fetal

quamous cells in pulmonary arteriallood from surviving women. The rou-ine use of transesophageal echocardiog-aphy in patients with AFE for evaluatingemodynamic changes to guide treat-ent more precisely should be encour-

ged. Selective pulmonary vasodilators,uch as nitric oxide for the treatment ofevere pulmonary hypertension duringhe acute phase of AFE, and recombinantctivated factor VIIa for managing severeIC resistant to conventional treat-ents deserve further study. Finally, fu-

ure research about the pathophysiology,arly diagnosis, and management can fo-us on the role of inflammatory media-ors, such as histamine, prostaglandins,nd leukotrienes, whose biologic activityan explain many of the events that oc-ur with AFE. f

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4

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us managed with uterine artery embolization.an J Anaesth 2003;50:917-21.38. Esposito RA, Grossi EA, Coppa G, et al.uccessful treatment of postpartum shockaused by amniotic fluid embolism with cardio-ulmonary bypass and pulmonary artery throm-oembolectomy. Am J Obstet Gynecol990;163:572-4.39. Van Heerden PV, Webb SA, Hee G, Cor-eron M, Thompson WR. Inhaled aerosolizedrostacyclin as a selective pulmonary vasodi-

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UPPLEMENTARY APPENDIX. Material and methodse searched Medline, Embase, Lilacs,

opline, and Cinahl (all from their in-eption to March 31, 2009), with noanguage restrictions and using the keyords “amniotic embolism” or “amni-tic embolus” to identify potentially eli-ible studies. The electronic search wasupplemented with additional studiesited as references in retrieved articles,ook chapters, and review articles, asell as reports on maternal mortality

rom surveillance systems. All of the po-entially relevant studies were retrievednd reviewed by the investigators, whoetermined inclusion based on scientificerit and clinical relevance. Method-

logical quality of observational studies,ase reports, and case series included inhe review were carefully assessed follow-ng the guidelines proposed for improv-ng the reporting of these studies, andnly articles agreed on by the authors toontain relevant and sufficient data fornterpretation were included in the re-iew. We gave priority to articles that
rovided the highest quality of evidence n
NOVEMBER 2009 American

nd drew the strongest conclusions pos-ible.

The searches produced 1071 articles,f which 147 were included in the review143 from computer search, 3 from re-orts on maternal mortality from sur-eillance systems, and 1 from referencesited in articles). No clinical trials (ran-omized or nonrandomized) on AFEere found. We identified only 2 popu-

ation-based cohort studies that investi-ated the association between AFE andeveral potential risk factors and 6 case-ontrol studies that evaluated tests pro-osed for the diagnosis of AFE in sus-ected cases. Thus, the majority oftudies identified were descriptive,

ainly case reports and case series.The overall incidence of AFE with 95%

onfidence interval (CI) was calculatedsing data from homogeneous largeopulation-based studies, which wereombined in a pooled analysis using aeighted method. Each incidence rateas multiplied by the number of deliver-

es in the study. This result was thenummed for all the studies and then di-ided by the sum of the weights. We didot consider it appropriate to performetaanalysis of studies evaluating other

opics on AFE, such as risk factors orests proposed for diagnosing AFE inuspected cases, because of the small
umber of studies included in the review.
Journal of Obstetrics & Gynecology 445.e11

2


4

. Incidence of amniotic fluid embolism and associated maternal and perinatal mortality around the world

Study, year Region, country PeriodNo. ofcases Incidencea

Maternalmortalityratio �100,000b

Maternalfatalityrate,% (95% CI)

Perinatalfatalityrate,% (95% CI)

Percentageof allmaternaldeaths

Steiner,2 1941 Chicago, USA, hospitalbased

1925-1940 8c NA 12.4 NA 63 (29–96) NA

................................................................................................................................................................................................................................................................................................................................................................................

Steiner,6 1949 Chicago, USA, hospitalbased

1932-1948 8c NA 6.0 NA NA NA

................................................................................................................................................................................................................................................................................................................................................................................

Barno,7 1959 Minnesota, USA 1952-1958 15c NA 2.7 NA NA NA................................................................................................................................................................................................................................................................................................................................................................................

Anderson,8 1967 Michigan, USA 1960-1965 32c NA 2.9 NA NA NA................................................................................................................................................................................................................................................................................................................................................................................

Liban,9 1969 Israel 1952-1966 14c NA 2.5 NA NA NA................................................................................................................................................................................................................................................................................................................................................................................

Watananukul,10 1979 Thailand, hospital based 1975-1978 5c NA 3.7 NA NA NA................................................................................................................................................................................................................................................................................................................................................................................

Morgan,11 1979 Several countries 1941-1978 272 NA NA 86 (82–90) NA NA................................................................................................................................................................................................................................................................................................................................................................................

Shinagawa,12 1983 Japan 1964-1980 15c NA NA NA NA 4.9................................................................................................................................................................................................................................................................................................................................................................................

Högberg,13 1985 Sweden, nation based 1951-1980 38c NA 1.2 67 (40–94)d 54 (38–69) 16.5d

................................................................................................................................................................................................................................................................................................................................................................................

Phuapradit,14 1985 Thailand, hospital based 1969-1982 3c NA 4.1 NA NA 11.5................................................................................................................................................................................................................................................................................................................................................................................

Agüero,15 1985 Venezuela, hospitalbased

1975-1981 4c NA 1.9 NA NA 1.0

................................................................................................................................................................................................................................................................................................................................................................................

Atrash,16 1990 USA, nation based 1979-1986 264c NA 0.9 NA NA 10.0................................................................................................................................................................................................................................................................................................................................................................................

Högberg,17 1994 Sweden, nation based 1980-1988 9c NA 1.0 NA NA 15.5................................................................................................................................................................................................................................................................................................................................................................................

Montiel,18 1994 Costa Rica, nationbased

1979-1988 12c NA 1.8 NA NA 4.7

................................................................................................................................................................................................................................................................................................................................................................................

Clark,19 1995 USA, nation based 1988-1994 46 NA NA 61 (47–75) 21 (6–36)e NA................................................................................................................................................................................................................................................................................................................................................................................

Pan,20 1995 Beijing, China, regionbased

1989-1993 29c NA 5.9 NA NA 15.5

................................................................................................................................................................................................................................................................................................................................................................................

Burrows,21 1995 Brisbane, Australia,hospital based

1984-1993 9 1/6594 3.4 22 (0–49) 33 (2–64) NA

................................................................................................................................................................................................................................................................................................................................................................................

Jenkins,22 1996 Ireland, nation based 1989-1991 2c NA 1.3 NA NA 10.5................................................................................................................................................................................................................................................................................................................................................................................

Fuentes,23 1998 Cuba, hospital based 1986-1995 4c NA NA NA NA 8.7................................................................................................................................................................................................................................................................................................................................................................................

Gilbert,24 1999 California, USA, statebased

1994-1995 53 1/20,646 1.3 26 (14–38) NA NA

................................................................................................................................................................................................................................................................................................................................................................................

Yang,25 2000 Suzhou, China, regionbased

1985-1999 38 NA NA 89 (80–99) NA 15.0

................................................................................................................................................................................................................................................................................................................................................................................

Maria,26 2001 France, nation based 1996-1997 16c NA NA NA NA 13.0................................................................................................................................................................................................................................................................................................................................................................................

Jegasothy,27 2002 Malaysia, nation based 1995-1996 16c NA NA NA NA 2.5................................................................................................................................................................................................................................................................................................................................................................................

Lau,28 2002 Singapore, nation based 1990-1999 16c NA 3.3 NA 60 (30–90)f 31.4................................................................................................................................................................................................................................................................................................................................................................................

Berg,29 2003 USA, nation based 1991-1997 275c NA 1.0 NA NA 8.6................................................................................................................................................................................................................................................................................................................................................................................

Troszynski,30 2003 Poland, nation based 1991-2000 90c NA 2.0 NA NA 19.5................................................................................................................................................................................................................................................................................................................................................................................

Welsch,31 2004 Bavaria, Germany,region based

1983-2000 18c NA 0.8 NA NA 7.8

................................................................................................................................................................................................................................................................................................................................................................................

Sullivan,32 2004 Australia, nation based 1973-1996 41c NA 0.7 NA NA 7.0................................................................................................................................................................................................................................................................................................................................................................................

King,33 2004 Australia, nation based 1997-1999 7c NA 0.6 NA NA 7.8................................................................................................................................................................................................................................................................................................................................................................................

Health Canada,34

2004Canada, nation based 1997-2000 7c NA 0.7 NA NA 10.9

................................................................................................................................................................................................................................................................................................................................................................................

Tuffnell,35 2005 United Kingdom, nationbased

1997-2004 44 NA 0.8 30 (17–45) 25 (12–38) NA

................................................................................................................................................................................................................................................................................................................................................................................

Conde-Agudelo. AFE: an evidence-based review. Am J Obstet Gynecol 2009. (continued )

45.e12 American Journal of Obstetrics & Gynecology NOVEMBER 2009

2(

3


. Incidence of amniotic fluid embolism and associated maternal and perinatal mortality around the worldcontinued)

Study, year Region, country PeriodNo. ofcases Incidencea

Maternalmortalityratio �100,000b

Maternalfatalityrate,% (95% CI)

Perinatalfatalityrate,% (95% CI)

Percentageof allmaternaldeaths

Kramer,36 2006 Canada, populationbased

1991-2002 185 1/16,318 0.8 13 (8–18) NA NA

................................................................................................................................................................................................................................................................................................................................................................................

Sullivan,37 2006 Australia, nation based 2000-2002 11c NA 1.5 NA 9 (0–26) 13.1................................................................................................................................................................................................................................................................................................................................................................................

Samuelsson,38 2007 Sweden, nation based 1971-1999 57 1/51,947 0.8 44 (31–57) NA NA................................................................................................................................................................................................................................................................................................................................................................................

Lewis,39 2007 United Kingdom, nationbased

1985-2005 77c NA 0.5 NA 44 (21–67)g 5.3

................................................................................................................................................................................................................................................................................................................................................................................

Abenhaim,40 2008 USA, population based 1999-2003 227 1/12,953 1.7 22 (16–28) NA NA................................................................................................................................................................................................................................................................................................................................................................................

Clark,41 2008 USA, health care systembased

2000-2006 13c NA 0.9 NA NA 13.7

................................................................................................................................................................................................................................................................................................................................................................................

Pallasmaa,42 2008 Finland, nation based 1997, 2002 2 1/55,359 NA NA NA NA................................................................................................................................................................................................................................................................................................................................................................................

Knight,43 2008 United Kingdom, nationbased

February2005-January2008

38 1/56,500 NA 24 (11–40) NA NA

................................................................................................................................................................................................................................................................................................................................................................................

Zhu,44 2009 Shanghai, China, regionbased

1996-2005 16 NA 1.8 NA NA 6.6

................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval; NA, not applicable or not available.a The denominator is the number of deliveries; b The denominator is the number of either live births or deliveries; c Only included fatal cases; d For the period 1972-1980; e For fetuses alive in utero

at the time of the event; f For 10 fatal cases; g For the triennium 2003-2005.

Conde-Agudelo. AFE: an evidence-based review. Am J Obstet Gynecol 2009.

. Signs and symptoms of amniotic fluid embolism recorded in large case series

Signs andsymptoms

Anderson,8

1967(n � 32), %

Peterson,88

1970(n � 40), %

Morgan,11

1979(n � 272), %

Clark,19

1995(n � 46), %

Gilbert,24

1999(n � 53), %

Yang,25

2000(n � 38), %

Hypotension 56 NR 27 100 47 100................................................................................................................................................................................................................................................................................................................................................................................

Pulmonary edemaor ARDS

NR NR 51 93 NR 100

................................................................................................................................................................................................................................................................................................................................................................................

Cardiopulmonaryarrest

59 30 NR 87 NR NR

................................................................................................................................................................................................................................................................................................................................................................................

Dyspnea 72 50 NR 48 NR NR................................................................................................................................................................................................................................................................................................................................................................................

Cyanosis 72 50 51 83 NR 100................................................................................................................................................................................................................................................................................................................................................................................

Coagulopathy 22 45 49 83 66 32................................................................................................................................................................................................................................................................................................................................................................................

Seizure 41 20 10 48 NR 16................................................................................................................................................................................................................................................................................................................................................................................

Fetal distress NR NR NR 100 49 NR................................................................................................................................................................................................................................................................................................................................................................................

ARDS, adult respiratory distress syndrome; NR, not reported.Conde-Agudelo. AFE: an evidence-based review. Am J Obstet Gynecol 2009.

NOVEMBER 2009 American Journal of Obstetrics & Gynecology 445.e13

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embolia amniótica - revisão 2009