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Consultant, Critical Care and Amniotic fluid embolism (AFE) is a rare complication of pregnancy carrying a high mortality
Anaesthesia, Wirral University Teaching rate. The exact pathogenesis of the condition is still not known. Diagnosing AFE needs a
Hospital, NHS Foundation Trust, high suspicion as it is essentially a clinical diagnosis of exclusion. Patients with AFE are
Upton, Wirral, UK, 1Department of best-managed in a critical care unit by a multidisciplinary team and management is largely
Anaesthesiology, All India Institute of supportive. This review compiles the currently available information on AFE.
Medical Sciences, New Delhi, India
Address for correspondence:
Dr. Girendra Sadera,
Consultant, Critical Care and Anaesthesia,
Wirral University Teaching Hospital, NHS
Foundation Trust, Upton, Wirral, CH49 5PE, UK.
E-mail: girendra.sadera@nhs.net Key words: Amniotic, embolism, fluid, pregnancy
Journal of Obstetric Anaesthesia and Critical Care / Jan-Jun 2015 / Vol 5 | Issue 1 3
Sadera and Vasudevan: Amniotic fluid embolism
RISK FACTORS this could not explain the entire clinical manifestations of the
syndrome. Moreover, this mechanism could not be proved in
Many risk factors have been associated with AFE, but causality animal studies.[15,16]
has not been proved for most of them though a consistent
At present, AFE is thought to result from an immune-mediated
association has been observed with older maternal age and
mechanism, given its similarity to septic shock or anaphylactic
medical induction of labor.[1] According to data from the UK
shock. It results from an abnormal immunological response of
and Ireland, confidential enquiries into maternal deaths and
the mother following exposure to fetal antigens leading to the
morbidity 2009-2012 labor induction or augmentation was done
release of various pro-inflammatory mediators.[13] Clark et al. even
in six out of eleven women who died of AFE in 2009-12 and three
proposed to rename the syndrome as “anaphylactoid syndrome
out of eleven had uterine hyper-stimulation.[6] The associated risks
of pregnancy,”[11] though it was not widely accepted. The exact
are mentioned in Table 1.[8-12] Instrumental delivery, caesarean
immunological mechanism is still unknown. Amniotic fluid itself
delivery, cervical trauma or uterine rupture may be the result
contains various vasoactive and prothrombotic substances such as
of attempting to deliver the fetus after an AFE and may not
platelet activating factor, interleukin 1 (IL-1), tumor necrosis factor-
be causative.[8] Some authors are of the opinion that uterine
alpha (TNF α), leukotrienes C4 and D4, endothelin, tissue factor,
stimulation is the least likely time for amniotic fluid to come into
arachidonic acid, and others which when released into the maternal
contact with the maternal circulation, thereby questioning the
circulation can lead to vasoconstriction, bronchoconstriction and
causative role of uterine stimulation.[13] Thus, no significant risk coagulation.[17] An anaphylactic mechanism is supported by
factor has been proved yet to change the current obstetric practice. studies showing increased mast cell degranulation[18] and refuted
The risk of recurrence of the condition is also not known, though by studies that failed to show a rise in serum tryptase levels.[19]
there are a few reports of successful subsequent pregnancies.[14] Complement activation as the primary mechanism has been
proposed.[20] The levels of complement factors C3 and C4 have
PATHOGENESIS been found to be reduced in patients with AFE. Furthermore, mast
cells can be secondarily activated after complement activation.
Exposure of the maternal circulation to amniotic fluid or fetal Platelet aggregation and neutrophil activation are also other
antigens is universally accepted as a prerequisite for AFE to occur. mechanisms proposed for the release of inflammatory mediators
This can occur through one of the three routes - uterine trauma that ultimately lead to the clinical syndrome.[17]
sites, endocervical veins or placental attachment site.[14] Minor
uterine trauma occurs at the time of normal labor as well as The reason for activation of the coagulation cascade is
instrumental or cesarean delivery. The exact mechanism underlying incompletely understood. Tissue factor in amniotic fluid and
the occurrence of AFE after this exposure is still not known. apoptotic amniotic cells may initiate the coagulation cascade,
but it is still doubtful if the small quantities of these factors
Historically, AFE was thought to be caused due to mechanical could lead on to the disseminated intravascular coagulation
obstruction of pulmonary vessels by amniotic fluid embolus (DIC) picture that is seen in AFE.[13]
consisting of fetal squames, vernix caseosa, lanugo hair,
trophoblasts, fetal gut mucin, and bile stained meconium. But Recently, an integrated mechanism was proposed. According
to this theory, activation of the coagulation cascade can
Table 1: Risk factors associated with amniotic fluid
lead to microthrombi in pulmonary vessels and add on to
embolism the mechanical obstruction by amniotic fluid components.
Age >35 years This, along with the various inflammatory mediators like
Multiparity leukotrienes can cause the complete picture of the syndrome.[21]
Male fetus An overview of the pathogenesis of AFE is shown in Figure 1.
Medical induction of labor
Instrumental delivery CLINICAL FEATURES
Caesarean delivery
Cervical trauma
Uterine rupture About 70% of cases occur during labor, 19% during cesarean
Uterine hyperstimulation section, and 11% after delivery in the immediate postpartum.[22]
Preeclampsia There have been reports of delayed AFE occurring up to 48 h
Eclampsia after delivery.[14] There are also reports of cases occurring after
Placenta previa second-trimester abortions, amniocentesis, blunt abdominal
Placental abruption trauma, abdominal surgeries, dilatation and evacuation, and
Ethnic minority
intrapartum amnioinfusion with normal saline.[23,24]
4 Journal of Obstetric Anaesthesia and Critical Care / Jan-Jun 2015 / Vol 5 | Issue 1
Sadera and Vasudevan: Amniotic fluid embolism
The classical form of AFE presents as a sudden onset respiratory with the classical subtype which was associated with a higher
distress followed by a sudden cardiovascular collapse. This incidence of sudden death.[26]
is followed by cardiac arrest and/or coagulopathy.[13] The
signs and symptoms in this early phase include dyspnea, DIAGNOSIS
desaturation, hypotension, cardiac arrhythmias, seizures, loss
of consciousness, bleeding, and cardiac arrest.[13] Fetal hypoxia Amniotic fluid embolism is essentially a clinical diagnosis and a
and bradycardia are almost universal if AFE occurs prior diagnosis of exclusion as there is no available laboratory test to
to delivery. Premonitory symptoms of tingling, numbness, confirm the diagnosis. The classical triad of respiratory distress,
restlessness, and agitation have been described and are thought cardiovascular collapse, and coagulopathy makes it easy to
to occur from early hypoxia.[9] The cause of cardiac arrest can be diagnose the classical form.[13] Different national registries
hypoxia, direct myocardial suppression or excessive bleeding.[11] have their own entry criteria but share common features
Lung injury and acute respiratory distress syndrome (ARDS) involving the classical triad along with a criterion to describe
are seen in the late phase. Multiple organ dysfunction and the timing of occurrence of the syndrome.[11,25] Other similar
hypoxic brain damage are common in those who survive the conditions need to be excluded before a diagnosis of AFE is
initial cardiac arrest. Infants born to these mothers are at risk made [Table 2].[6,14,27,28] The UK Obstetric Surveillance System
for hypoxic ischemic encephalopathy and cerebral palsy.[25] diagnostic criteria for AFE are given in Table 3.[10]
In the atypical form, coagulopathy manifesting as severe bleeding Table 2: Differential diagnoses of AFE
occurs in the absence of cardiopulmonary manifestations.[13] Nonobstetric causes
Uterine atony can additionally contribute to the hemorrhage. Pulmonary embolism (air, fat, thrombi)
Pulmonary edema
Tension pneumothorax
Studies utilizing transesophageal echocardiography have
Cardiac - myocardial infarction, heart failure, arrhythmias, tamponade
found that the cardiac abnormalities in AFE are biphasic – an
Anaphylaxis
early transient phase of intense pulmonary vasoconstriction, Septic shock
pulmonary hypertension, and right ventricular failure, and a Aspiration
late phase of left ventricular dysfunction leading to hypotension Anesthesia related - local anesthetic toxicity, high spinal
and cardiogenic pulmonary edema.[14] Other reversible causes - toxins, hypo/hyperkalemia, metabolic,
hypothermia
Obstetric causes
Tsunemi et al. attempted to classify 136 cases of AFE into
Eclampsia
three subtypes: Abruptio placenta
1. Classical subtype with early respiratory distress and hypoxia, Uterine rupture
2. Anaphylactoid subtype with early cardiac dysfunction and Postpartum hemorrhage
arrhythmias and Peripartum cardiomyopathy
3. DIC subtype with coagulopathy. AFE: Amniotic fluid embolism
They found considerable overlap of features in many patients. Table 3: UKOSS diagnostic criteria
The DIC subtype carried a lesser mortality when compared Either - In the absence of any other clear cause
Acute maternal collapse with one or more of the following
Acute fetal compromise
Cardiac arrest
Cardiac arrhythmias
Hypotension
Maternal hemorrhage
Coagulopathy
Premonitory symptoms
Seizure
Shortness of breath
Excluding women with maternal hemorrhage as the first presenting
feature in whom there was no evidence of early coagulopathy or
cardio-respiratory compromise
Or
Women in whom the diagnosis was made at postmortem examination
with fetal squames or hair in the lungs
Figure 1: Pathophysiology of amniotic fluid embolism UKOSS: UK obstetric surveillance system
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Sadera and Vasudevan: Amniotic fluid embolism
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Sadera and Vasudevan: Amniotic fluid embolism
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Cite this article as: Sadera G, Vasudevan B. Amniotic fluid embolism. J Obstet
Anesth 2013;22:329-36.
Anaesth Crit Care 2015;5:3-8.
36. Johnston TA, Grady K. Maternal Collapse in Pregnancy and the
Puerperium. Green-top Guideline No. 56. London (UK): Royal College Source of Support: Nil, Conflict of Interest: None declared.
8 Journal of Obstetric Anaesthesia and Critical Care / Jan-Jun 2015 / Vol 5 | Issue 1
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