Arch Gynecol Obstet (2008) 277:271275

DOI 10.1007/s00404-007-0489-z
1 3
CASE REPORT
Amniotic Xuid embolism managed with success during labour:
report of a severe clinical case and review of literature
A. Peitsidou P. Peitsidis V. Tsekoura A. Spathi
A. Tzaneti E. Samanta G. Siampalioti E. Kioses
Received: 7 July 2007 / Accepted: 4 October 2007 / Published online: 20 November 2007
Springer-Verlag 2007
Abstract
Background AFE (amniotic Xuid embolism) is widely
known as a disastrous rapid-progressing clinical entity. The
incident ranges from 1:800 to 1:8,000. The mortality rate
reaches 6186%. Neonatal survival is reported at 70%.
Methods We describe the case of a healthy 29-year old
primigravida developing amniotic Xuid embolism during
labour. Acute respiratory failure and hypotension combined
with seizures were the initial symptoms. The patient under
went an urgent caesarean section with extreme blood loss,
complicated by disseminated coagulopathy.
Results A total hysterectomy was performed due to pro-
fuse bleeding. Aggressive management was practiced with
continuous transfusion of blood products and administra-
tion of vasocopressors.
Conclusion Amniotic Xuid embolism or anaphylactoid
syndrome of pregnancy is a life-threatening condition.
Diagnosis is one of the exclusion. Its management is very
diYcult and requires quick management and cooperation of
physicians from diVerent specialities.
Keywords AFE Caesarean section Hysterectomy
CPR Coagulopathy
Introduction
Amniotic Xuid embolism (AFE) is a rare, unpredictable
life-threatening complication unique to pregnancy. It was
Wrst described by Meyer in 1926 [1]. Steiner and Luschb-
augh were those who established and recognised AFE as a
clinical entity in 1941, examining eight mortality case
series of women who died suddenly during labour [2].
AFE incidence ranges from 1:800 to 1:8,000 of pregnan-
cies and mortality rate reaches 6186% [3, 4]. It is esti-
mated that 10% of all maternal deaths are caused by AFE
[3, 4]. The clinical presentation encompasses a spectrum of
diseases from mild subclinical organ pathology to severe
cardiopulmonary arrest, coagulopathy and fatal outcome
[3, 4].
Clark et al. [4] have proposed an altered name for AFE
giving the speciWcation anaphylactoid syndrome of preg-
nancy because of the various humoral and immunologic
factors implicated.
Case report
A healthy 29-year-old primigravida at 40 weeks gestation
was admitted for stimulation of labour in our hospital. The
patient showed vertex presentation, cervix dilatation of
5 cm, ruptured uterine membranes and a foetal heart rate of
140 bpm. During the process of labour when cervix dilata-
tion was 7 cm the patient suddenly presented acute respira-
tory failure, cyanosis, tonic-clonic seizures, hypotension
85/45 mmHg, followed by cardiovascular collapse. Severe
A. Peitsidou P. Peitsidis (&) G. Siampalioti E. Kioses
Obstetrics and Gynecology Department,
Alexandra General Hospital, Athens, Greece
e-mail: peitsidi@ath.forthnet.gr
V. Tsekoura E. Samanta
Anesthesiology Department,
Hippokrateion General Hospital, Athens, Greece
A. Spathi A. Tzaneti
Anesthesiology Department,
Alexandra General Hospital, Athens, Greece
272 Arch Gynecol Obstet (2008) 277:271275
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decelerations were shown in cardiotocograph (CTG)
(Fig. 1). Crash intubation was performed immediately
within 2 min with i.v. infusion of propofol 100 mg, fenta-
nyl 100 g and succinylcholine 100 mg.
The patient was transferred to the operating room within
5 min. Emergency caesarean section was performed, result-
ing in the delivery of a viable male infant weighing 3,890 g.
with an APGAR score of 2 at 2 min and severe bradycardia
6070 bpm who, after successful cardiopulmonary resusci-
tation, was transferred to the Neonatal Intensive Care Unit.
Umbilical artery cord blood pH value was 7.24. As the
patient was under mechanical ventilation, a catheter on the
right internal jugular vein and radial artery was placed, for
the infusion of intravenous Xuids. After the delivery the
woman presented sinus tachycardia 140 bpm leading to
sudden cardiac arrest. Urgent advanced life support was ini-
tiated, systemic cardiac compressions and i.v. infusion of
noradrenaline 8 g/kg per min were given. The patient
managed to overcome the cardiac arrest and sinus rhythm
was established de novo. At that time patients blood pres-
sure dropped again to 70/30 mmHg, dopamine was infused
10 g/kg per min, suddenly profuse bleeding through the
laparotomy wound, nose, mouth and vagina occurred, thus
inducing coagulopathy. Three units of packed red blood
cells and four units of fresh frozen plasma were infused.
The blood loss was estimated to 3,000 ml. Laboratory Wnd-
ings were: Hgb 6.8 g/dl; arterial blood gases: pH 6.91,
pCO
2
60 mmHg, pO
2
110 mmHg and HCO
3

11 mmol/l;
base excess 21 mmol/l. Liver enzymes and biochemical
examinations were normal. Haemorrhagic control revealed
a severe coagulopathy with a Wbrinogen level of 0.45 g/l,
international normalized ratio (INR) of 1.8, activated par-
tial thromboplastin time (aPTT) of 49 s, prothrombin time
(PT) of 21 s and platelet count of 110,000/l. The level of D-
Dimer Plus was 4,980 with normal range (50228). The
uterus was not contracted (despite continuous massaging
and synchronous i.v. infusion of methergine 0.2 mg). Due
to continuous profuse bleeding worsened by uterine atony,
an abdominal hysterectomy with conservation of the ova-
ries was performed. Aggressive treatment of the coagulopa-
thy consisted of transfusion of three units of packed red
blood cells (RBC), four units of fresh frozen plasma (FFP)
and cryoprecipitate. HypoWbronogenemia was managed
with 2 g i.v. infusion of Wbrinogen. Seven hours after the
onset of acute symptomatology, the patient became haemo-
dynamically stable. Blood pressure was increased reaching
100/65 mmHg. An elevation was noticed in the levels of
Wbrinogen by 1 g/l and aPTT by 39 as well. The level of
INR reached 1.7 s. The bleeding stopped progressively, the
patient was transferred intubated in the Intensive Care Unit
(ICU) under synchronized intermittent mechanical ventila-
tion (SIMV) support and continuous dopamine infusion. A
triple combination of antibiotics was administered. Twenty-
four hours post partum a decrease in the level of Hgb
6.4 g/dl was observed in the ICU. Physical examination
revealed dome-shaped, distented abdomen. U/s conWrmed
the existence of intraabdominal Xuid. The patient under-
went a second exploratory laparotomy resulting in the com-
plete management of the haemorrhage. Haemostasis was
achieved after ligation of a bleeding artery. About 1,000 ml
of the blood was collected from the abdominal cavity.
Another 2 U of packed red-blood cells were transfused,
thus increasing THE levels of Hgb up to 8 g/dl. The patient
remained intubated in the ICU for 3 days. Transfusion with
2 U of RBC and FFP led to the correction of coagulopathy.
Thrombocytopenia was treated with infusion of 4 U of
Fig. 1 CTG changes during
labour and presentation of
decelerations after AFE
Arch Gynecol Obstet (2008) 277:271275 273
1 3
platelets in the rate of 2 U before and 2 U after the laparot-
omy. Its number elevated during the second post-operative
day (Table 1). X-ray of the chest referred about atelectasis
and minimal alveolar inWltrates. Pulmonary scintigraphy
with Tc-99 m MAA (3 mCi) assisted diagnosis, showing
bilateral lack of perfusion (possibility of pulmonary embo-
lism) (Fig. 2). CT of the chest conWrmed the Wnal diagnosis.
After 3 days, the patient was extubated and transferred to
the department in good clinical condition. The patient was
somewhat confused and developed partial loss of orienta-
tion. MRI of the brain was normal. After 10 days the
patients condition gradually improved and she was dis-
charged to home with complete resolution of the patients
symptoms. No pathological complications were observed
during her follow-up. The follow-up included monthly
detailed blood analysis and cardiological examinations with
ultrasound and ECG (electrocardiogram) for 6 months.
The patients infant resuscitated in the Intensive Neona-
tal Care Unit for 20 days and did not present any short- or
long-term neurodevelopmental sequelae. The Wnal diagno-
sis was AFE leading to acute cardiopulmonary insuY-
ciency and post-partum DIC.
Discussion
AFE is a devastating complication of pregnancy. Diagnosis
is diYcult and requires a high level of suspicion. In our case
although it was not conWrmed histologically the co-exis-
tence of pregnancy with cardiopulmonary failure and DIC,
strongly supports the fact that AFE is the most propable
diagnosis for this clinical case.
Clark [4] from USA and TuVnel [5] in UK were worked
systematically on this issue providing a national registry for
suspected AFE. Entry criteria consist of the presence of the
following four factors:
1. Acute hypotension or cardiac arrest.
2. Acute hypoxia.
3. Coagulopathy or severe clinical haemorrhage in the
absence of other explanations.
4. All of these occurring during labour, caesarean deliv-
ery, or D & E or within 30 min post-partum with no
other explanation for the Wndings [4, 5].
Hypotension is the major early manifestation presenting in
100% of all severe cases [4]. The basic pathogenesis
derives from the pulmonary arteriolar vasospasm due to
acute obstruction by foetal debris leading to secondary left
ventricular insuYciency and profound hypotension [6].
Acute hypoxia appears in 90% of the cases and it is the
cause of mismatching of ventilation and perfusion in AFE
[4]. Non-cardiogenic pulmonary oedema is developed in
70% of the patients possibly due to the eVect of various
mediators of anaphylaxis histamine, bradykinins leading to
capillary leak syndrome [7]. Coagulopathy is found in 83%
of the patients with AFE. Half of these patients may
develop coagulopathy within 4 h from the onset of the clin-
ical symptoms. The aetiology of the haemorrhage is
obscure and it is thought that consumptive coagulopathy
may lead to it [8]. In contrast, increased Wbrinolysis has
been shown to occur in AFE and it has been suggested that
an elevated plasminogen activator inhibitor-1 antigen in
amniotic Xuid may become active in the maternal blood and
contribute to DIC [9]. The pathophysiology of AFE is not
completely understood. It is a process that involves a chain
reaction of many mediators of inXammation like the prosta-
glandins (E1, E2, F1), leukotrienes, platelet-activating fac-
tors and complement-activating factors which are elevated
during labour [10]. These pathophysiological mechanisms
present similarity with reactions that take part in anaphy-
laxis and septic shock suggesting the term AFE to be a
Fig. 2 Scintigraphy with Tc99 m, arrows show lack of perfusion
Table 1 Coagulation values
during the diVerent phases
of the clinical case
Preoperative Intraoperative ICU 24 h 48 h Normal range
Hgb (g/dl) 10.6 6.9 6.4 8.0 9.9 11.614.6
Platelets (10
3
) 240 110 87 76 105 156369
PT (s) 11.0 21.0 18.0 14.0 11.9 1015
APTT (s) 28.7 49 39 31.3 26.4 26.036.0
INR (s) 1.0 1.8 1.7 1.24 1.08 0.901.20
Fibrinogen (g/l) 2.50 0.45 1.10 1.30 1.80 1.803.50
D-Dimers (/l) 150 4,980 3,540 2,800 1,670 50228
ICU intensive care unit, Hgb
haemoglobin, PT prothrombin
time, APTT activated partial
thromboplastin time, INR inter-
national normalized ratio
274 Arch Gynecol Obstet (2008) 277:271275
1 3
misnomer [4]. Normally, the intact foetal membranes do
not permit the entrance of the amniotic Xuid in the maternal
circulation. AFE occurs only when there is a breach in this
barrier [11]. There are three routes where the normal barrier
may breakdown. They include endocervical veins, uterine
trauma sites and the placental attachment site. Medical
induction of labour seems to increase the risk of amniotic
embolism [12]. Maternal age of 35 years or older, caesar-
ean or instrumental vaginal delivery, polyhydramnios, cer-
vical laceration or uterine rupture, placenta previa or
abruption, eclampsia and foetal distress were also associ-
ated with an increased risk [12].
Male foetus is considered to be a risk factor for the
development of AFE [4]. In our case we had a male deliv-
ery. Diagnosis is assisted by the clinical signs mentioned in
the national registry [13]. In our case all the clinical symp-
tomatology was very clear and obvious. In Clarks series it
is reported that 79% of the infants survived and only 50%
were neurologically normal [4]. In our case, the infant sur-
vived and remained neurologically intact after the emer-
gency caesarean section, but the clinical condition of the
mother deteriorated after the rapid activation of DIC.
The presence of foetal squamous cells in pulmonary
blood received by pulmonary-catheterisation is not always
pathognomic for AFE. Clark et al. [13] stated that foetal-
squamous cells might be found in pregnant women after
pulmonary catheterisation. These patients were catheterised
for several reasons but they did not develop AFE.
New methods for rapid diagnosis have been worked-out.
The detection of zinc-coproporphyrin I in the maternal
plasma and TKH-2 monoclonal antibody reaction with
mucin are known new methods established by Kanayama
[14] and Kobayashi [15], respectively. The detection of the
mediator of anaphylaxis tryptase may also serve as a diag-
nostic tool [16].
There are no speciWc manners of management of AFE.
Treatment is supportive and should be prompt. It has three
basic directives: rapid initiation and continuation of oxy-
genation, circulatory support and correction of coagulopa-
thy [12]. The main aspect is the prevention of hypoxia
leading to multiple organ failure. Normal saturation is
maintained via early intubation and mechanical ventilation
with 100% oxygen. Circulatory stabilisation is achieved
with induction of crystalloids and vasopressor agents like
adrenaline, dopamine and atropine. Transoesophageal
echocardiography can oVer useful assistance in estimating
left ventricular Wlling so that appropriate Xuid therapy is
guided [17]. The coagulopathy depends from the level of
haemorrhage. It may be successfully treated as it was
achieved in our case with the infusion of blood products,
FFP, Wbrinogen, cryoprecipitates and platelets if thrombo-
cytopenia is present. Newer clinical studies suggest the use
of recombinant factor VIIa in the treatment of DIC [18].
Hypersensitivity reactions are treated with corticoste-
roids and antihistamines (H1/H2 blockers). The combina-
tion of uterine atony with DIC is a life-threatening
complication that requires immediate and invasive surgical
intervention. Ligation or embolisation of uterine artery,
ligation of inguinal artery and hysterectomy are cardinal
surgical interventions and we can practice these in AFE
[19]. In our case hysterectomy was aggressive and spoils
the patients fertility state but this surgical solution is heroic
and life-saving.
Critical point in the treatment is the delivery of the foe-
tus, which should be as quick as possible. When a cardiac
arrest is monitored the risk of neonatal hypoxia is
extremely high. OShea [20] states that foetus should be
delivered within 34 min from the onset of cardiac arrest.
Severe vanguard therapeutic options have been used
recently including cardiopulmonary bypass (CPB), extra-
corporeal membrane oxygenation and intra-aortic balloon
counter pulsation [19, 21]. Monitoring of the patient with
suspected AFE includes continuous evaluation with elec-
trocardiography and pulse oximetry. Blood pressure moni-
toring should be performed without interruption if possible.
Large bore intravenous access is essential for resuscitation.
A central venous pressure catheter or pulmonary artery
catheter should be placed early in the resuscitation and may
assist the management of the patient.
Conclusion
AFE is widely recognised as an unpredictable and cata-
strophic complication of pregnancy. Its mortality rate
reaches 86%. Neonatal survival is reported at 70% [12].
Prompt management and resuscitation have succeeded in
improving the prognosis. The exact pathophysiological
mechanisms that boost this lethal clinical entity are not
completely understood. Diagnosis demands a high level of
suspicion and without doubt is one of exclusion. AFE can
occur at any time of gestation. The clinical case we pre-
sented was most likely to be AFE. The maternal and neona-
tal resuscitation was accomplished successfully despite the
sad fact of hysterectomy. The current resuscitation is the
product of a rapid and organised teamwork of many speci-
alities involved in this disastrous clinical event.
References
1. Meyer JR (1926) Embolia pulmonar amnio caseosa. J Bras Med
2:301303
2. Steiner PE, Lushbaugh CC (1941) Maternal pulmonary embolism
by amniotic Xuid. JAMA 117:12451254
3. Morgan M (1979) Amniotic Xuid embolism. Anaesthesia 34:20
32
Arch Gynecol Obstet (2008) 277:271275 275
1 3
4. Clark SL, Hankins GD, Dudley DA, Dildy GA, Porter TF (1995)
Amniotic Xuid embolism: analysis of the national registry. Am J
Obstet Gynecol 172:11581167
5. TuVnell DJ (2005) United Kingdom amniotic Xuid embolism reg-
ister. BJOG 112:16251629
6. Girard P, Mal H, Laine JP et al (1986) Left heart failure in amni-
otic Xuid embolism. Anesthesiology 64:262265
7. Turner R, Gusack M (1984) Massive amniotic Xuid embolism.
Ann Emerg Med 13:359361
8. Harnett MJP, Hepner DL, Datta S et al (2005) EVect of amniotic
Xuid on coagulation and platelet function in pregnancy: an evalu-
ation using thromboelastography. Anaesthesia 60:10681072
9. Estelles A, Gilabert J, Andres C et al (1990) Plasminogen activator
inhibitors type 1 and type 2 and plasminogen activators in amni-
otic Xuid during pregnancy. Thromb Haemost 64:281285
10. Karetzky M, Ramirez M (1998) Acute respiratory failure in preg-
nancy. An analysis of 19 cases. Medicine 77:4149
11. Roche WD Jr, Norris HJ (1974) Detection and signiWcance of mater-
nal pulmonary amniotic embolism. Obstet Gynecol 43:729731
12. Kramer MS, Rouleau J, Baskett TF, Joseph KS, The Maternal
Health Study Group of the Canadian Perinatal Surveillance
System (2006) Amniotic Xuid embolism and medical induction of
labour: a retrospective, population-based cohort study. Lancet
368(9545):14441448
13. Clark SL, Pavlova Z, Geenspoon J, Horenstein J, Phelan JP (1986)
Squamous cells in the maternal pulmonary circulation. Am J
Obstet Gynecol 154:104106
14. Kanayama N, Yamazaki T, Naruse H, Sumimoto K, Horiuchi K,
Terao T (1992) Determining zinc coproporphyrin in maternal plas-
maa new method for diagnosing amniotic Xuid embolism. Clin
Chem 38:526529
15. Kobayashi H, Ohi H, Terao T (1993) A simple, noninvasive,
sensitive method for diagnosis of amniotic Xuid embolism by
monoclonal antibody TKH-2 that recognizes NeuAc 2-6GalNAc.
Am J Obstet Gynecol 168:848853
16. Benson MD, Lindberg RE (1996) Amniotic Xuid embolism, ana-
phylaxis, and tryptase. Am J Obstet Gynecol 175:737
17. James CF, Feinglass NG, Menke DM et al (2004) Massive amni-
otic Xuid embolism: diagnosis aided by emergency transesopha-
geal echocardiography. Int J Obstet Anesth 13:279283
18. Lim Y, Loo CC, Chia V et al (2004) Recombinant factor VIIa after
amniotic Xuid embolism and disseminated intravascular coagulop-
athy. Int J Obstet Anesth 87:178179
19. Stanten RD, Iverson LI, Daugharty TM et al (2003) Amniotic Xuid
embolism causing catastrophic pulmonary vasoconstriction: diag-
nosis by transesophageal echocardiogram and treatment by cardio-
pulmonary bypass. Obstet Gynecol 102:496498
20. OShea A, Eappen S (2007) Amniotic Xuid embolism. Int Anes-
thesiol Clin 45(1):1728
21. Hsieh YY, Chang CC, Li PC et al (2000) Successful application of
extracorporeal membrane oxygenation and intra-aortic balloon
counterpulsion as lifesaving therapy for a patient with amniotic
Xuid embolism. Am J Obstet Gynecol 183:496497