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Amniotic fluid embolism
Jason Moore, MD; Marie R. Baldisseri, MD
Incidence: Amniotic fluid embolism is a catastrophic syndrome
that occurs during pregnancy or in the immediate postpartum
period. Multiple case reports have described the clinical findings
and have reported variable success with supportive care. There
has been discrepancy with respect to the incidence and mortality
of amniotic fluid embolism. One likely explanation for this inconsistency is the lack of sensitive and specific diagnostic studies to
definitively identify cases of amniotic fluid embolism, leading to
both over- and underreporting. Despite the variation in reported
incidence and mortality, amniotic fluid embolism remains a lifethreatening condition with significant morbidity and mortality for
the pregnant woman. It is the fifth most common cause of
maternal mortality in the world.
Diagnosis: The diagnosis of amniotic fluid embolism continues
to be a clinical diagnosis and a diagnosis of exclusion based on
the rapid development of a complex constellation of findings with
sudden cardiovascular collapse, acute left ventricular failure with
pulmonary edema, disseminated intravascular coagulation, and
neurologic impairment. Given the significant morbidity and mor-
A
lthough it was first described
in 1926 (1), amniotic fluid embolism was not recognized as a
syndrome until 1941, when
Steiner and Lushbaugh reported an autopsy series showing fetal mucin and
squamous cells in the pulmonary vasculature of eight women who died of sudden
shock during labor (2). Incidence worldwide varies between 1 in 8,000 and 1 in
83,000 live births, and mortality is between 61% and 86% with many of these
patients dying within the first hour after
presentation (3). A more recent U.S.
study reported an incidence of 1 in
20,646 singleton pregnancies and mortality as low as 26% (4). Amniotic fluid embolism syndrome accounts for approximately 10% of all maternal deaths in the
United States and can result in permanent neurologic deficits in up to 85% of
survivors (5). Clark et al. (5) proposed
changing the name of the syndrome from
From the Department of Critical Care Medicine,
University of Pittsburgh Medical Center, Pittsburgh, PA.
Copyright © 2005 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000183158.71311.28
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
tality associated with this condition, a high index of suspicion is
warranted. Suspected risk factors have included tumultuous labor, trauma, multiparity, increased gestational age, and increased
maternal age. However, many patients who develop amniotic fluid
embolism have no obvious risk factors.
Management: Patients with amniotic fluid embolus are best
managed using a multidisciplinary approach. There are no pharmacologic or other therapies that prevent or treat the amniotic
fluid embolism syndrome, and supportive care typically involves
aggressive treatment of multiple types of shock simultaneously.
In this article we discuss the clinical presentation of amniotic
fluid embolism syndrome as well as current opinions regarding
pathophysiology, diagnosis, and management. (Crit Care Med
2005; 33[Suppl.]:S279 –S285)
KEY WORDS: amniotic fluid embolism; life-threatening condition;
clinical diagnosis; diagnosis of exclusion; hypoxia; hypotension;
cardiogenic shock; neurologic impairment; disseminated intravascular coagulation; anoxic encephalopathy
“amniotic fluid embolus” to “anaphylactoid syndrome of pregnancy,” citing close
similarities between the manifestations of
amniotic fluid embolism and those of
anaphylactic and septic shock. Recent
studies have enhanced the understanding
of amniotic fluid embolism and sparked
new ideas with respect to definition, diagnosis, and management. Additionally,
several blood tests have been suggested as
diagnostic and prognostic indicators (3,
6 –9), and other substances have been implicated in the pathogenesis of amniotic
fluid embolism (10, 11).
Clinical Presentation
Amniotic fluid embolus syndrome
classically occurs acutely during labor
and delivery or in the immediate postpartum period. Rare exceptions to this timing of onset have been reported as late as
48 hrs postpartum or following cesarean
delivery, amniocentesis, or removal of the
placenta or with first and second trimester abortions (12–14). Risk factors that
have been previously attributed to the
development of amniotic fluid embolus
include turbulent labor, trauma, multiparity, use of oxytocin, increased mater-
nal age, increased gestational age, male
fetus, and cesarean section. Support for
the association of these various factors to
amniotic fluid embolus has been inconsistent (4, 5).
The cardinal findings of amniotic fluid
embolus are hypoxia, hypotension with
shock, altered mental status, and disseminated intravascular coagulation (Table 1).
These findings are typically present at or
shortly after initial presentation with an
incidence of between 80% and 100% (5).
Rapid patient deterioration and death often
result from the abrupt onset and fulminant
course of these symptoms. Mortality has
been reported as high as 50% in the first
hour after presentation due to cardiopulmonary manifestations. Other common
presenting symptoms of amniotic fluid embolus include seizure activity, agitation, evidence of fetal distress, and maternal constitutional symptoms such as fever, chills,
nausea, vomiting, and headache (Table 2).
Since not all of these symptoms are evident
on patient presentation, the differential diagnosis for amniotic fluid embolus syndrome is broad (Table 3). In this section,
the major clinical findings of amniotic fluid
embolus listed above are reviewed in detail.
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Table 1. Cardinal signs/symptoms of amniotic
fluid embolism syndrome
Hypoxemia
Shock (typically obstructive, cardiogenic, or
distributive)
Coagulopathy/disseminated intravascular
coagulation
Altered mental status/hypoxic encephalopathy
Table 2. Other common presenting signs/
symptoms of amniotic fluid embolism
Seizure activity
Confusion
Agitation
Constitutional (fever, chills, headache, nausea,
vomiting)
Evidence of fetal distress (late decelerations,
bradycardia)
Table 3. Differential diagnosis of amniotic fluid
embolism
Pulmonary thromboembolism
Air embolism
Hemorrhage
Aspiration of gastric contents
Anesthetic complications
Anaphylaxis
Sepsis/systemic inflammatory response
syndrome
Myocardial infarction
Cardiomyopathy
Eclampsia
Transfusion reactions
Hypoxia. Hypoxia is an early finding
in amniotic fluid embolism and is present
in 93% of patients according to the national registry (5). It is often seen concomitantly with respiratory arrest and cyanosis during the initial presentation.
This initial hypoxia is likely due to severe
ventilation and perfusion mismatching,
which appears to develop from the inciting embolic event. Another explanation
for this early hypoxia may be cardiogenic
pulmonary edema, which develops as a
result of severe left ventricular dysfunction often seen in amniotic fluid embolism. Bronchospasm seems to be a less
likely cause for respiratory failure and
hypoxia, as it is noted in only 15% of
patients (5).A later phase of hypoxia is
also seen in patients with amniotic fluid
embolism. Although ongoing left ventricular impairment and cardiogenic pulmonary edema certainly may contribute to
this later hypoxia, up to 70% of patients
who survive the first several hours develop noncardiogenic edema coincident
with improvement in left ventricular
S280
function (15). Evidence lending support
to the development of capillary leak syndrome includes exudative edema fluid
that contains high protein concentration
and amniotic fluid debris. Although this
noncardiogenic edema is severe and
seems to result from profound alveolarcapillary membrane damage, the edema
tends to resolve more rapidly than the
typical clinical course of acute respiratory
distress syndrome. Hypoxia in both the
initial and later phases of amniotic fluid
embolism has been implicated in the development of widespread neurologic deficiencies and brain death. The cause of
these neurologic changes is thought to be
due to anoxic encephalopathy and may be
particularly severe when hypoxia is
present during seizure activity.
Although hypoxia is typically present
throughout the entire course of amniotic
fluid embolism, the underlying etiology
of hypoxia over that course seems to vary
over time between obstructive, cardiogenic, and inflammatory sources (Fig. 1).
As we will see in subsequent sections, this
concept seems to prevail in many of the
clinical manifestations to be reviewed.
Hypotension/Shock. Hypotension is
another early manifestation of amniotic
fluid embolism, and it is uniformly
present for patients with severe disease
(5). The etiology of shock most commonly described in case reports has been
cardiogenic shock from left ventricular
failure. Obstructive and distributive etiologies of shock have also been identified
(16 –19). The various causes of shock will
be presented here with respect to the
timing of the early and later phases of the
syndrome.Hemodynamic changes in the
time period immediately following presentation are less well known in humans
because the practice of ongoing invasive
hemodynamic monitoring in otherwise
healthy obstetrical patients is extremely
rare. Despite this, observational data and
results of animal models have provided
some insight into hemodynamic instability during the early phase of amniotic
fluid embolism. Animal models have
shown a transient increase in pulmonary
artery pressure shortly after introduction
of a homogeneous amniotic fluid bolus
(20). This transient pulmonary hypertension is thought to be due to pulmonary
vasospasm and the onset of left ventricular dysfunction (5, 20 –22). Systemic
blood pressure may be increased transiently at this time as well; however, since
the patient usually experiences respiratory distress at this time, causation has
not been established.
Shortly after the transient increase in
both pulmonary and systemic pressures,
blood pressure decreases precipitously
and shock develops. The etiology of shock
in this early phase may be multifactorial.
The presence of left ventricular dysfunction has been well documented using
echocardiography and measurements
from pulmonary artery catheters in patients with amniotic fluid embolism and
is likely present in both early and later
phases of the syndrome to some degree
(Fig. 2) (21, 23–29). Cardiac arrhythmias
including bradycardia, asystole, ventricular fibrillation, and pulseless electrical activity may also be present and complicate
management. In addition to cardiogenic
shock, several case reports have shown
evidence of obstructive shock with normal left ventricular function and impaired right ventricular function (16 –18,
30). One case report describes the performance of transesophageal echocardiography during the early phase of disease.
Findings included right ventricular failure, suprasystemic right-sided pressures,
bulging of the interatrial and interventricular septum from right to left, and
severe tricuspid regurgitation (30).
Shock during the later phase of the
syndrome is also likely to be multifacto-
Figure 1. Postulated relative contributions to hypoxemia in patients with amniotic fluid embolism.
Figure 2. Postulated relative contributions to
shock in patients with amniotic fluid embolism.
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
rial. Although evidence of cardiogenic
and obstructive shock may persist into
the later phase of disease, they tend to be
less hemodynamically significant over
time. As previously noted, patients who
survive the first several hours of amniotic
fluid embolism often have improvement
in left ventricular function but may develop noncardiogenic edema (15). Cardiac indexes from various reports range
between 2.1 and 6.9 (23). The higher cardiac index values, particularly when
taken in conjunction with noncardiogenic edema, suggest that a distributive,
“septic shock-like” process may be significant during the later phase of amniotic
fluid embolism due to increased inflammation (Fig. 2).
Hypovolemic or hemorrhagic shock
seems to develop less commonly in patients with amniotic fluid embolism. This
is likely due to the physiologic changes
that are found in pregnant patients including increased red blood cell mass and
plasma volume, as well as the autotransfusion and reclaiming of third-spaced fluids that typically occur shortly after delivery. Additionally, patients are typically
resuscitated with large volumes of crystalloid and colloid, particularly when coagulopathy (reviewed subsequently) develops. It certainly remains possible that
hypovolemic shock could develop, especially if hemorrhage is severe.
Shock is a poor prognostic factor in
patients who develop amniotic fluid embolism. Like hypoxia, the underlying
cause of hypotension in these patients
seems to follow a temporal pattern that
may include all different forms of shock
(31). Considering that these forms of
shock may be present simultaneously, it
is not difficult to see why mortality is
high in severely affected patients.
Coagulopathy/DIC. Disseminated intravascular coagulation (DIC) may be
present in up to 83% of patients with amniotic fluid embolism, and half of these
patients develop coagulopathy within 4 hrs
of initial presentation (5). Typically, the
presenting manifestation of DIC is profound hemorrhage, prompting an extensive
search for anatomical causes of bleeding.
The onset of DIC is variable, and it may be
seen in either the early phase or later
phases of the syndrome. Coagulopathy may
be present concurrently with cardiopulmonary symptoms, following cardiopulmonary symptoms, or without cardiopulmonary symptoms as the main clinical
manifestation (32, 33). DIC in amniotic
fluid embolism may develop early as a reCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
sult of substances in the amniotic fluid
itself or later from the systemic inflammatory response that may arise along with
noncardiogenic edema. Diffuse bleeding
that results from DIC may lead to hemorrhagic shock and death.
Altered Mental Status. Encephalopathy is a common occurrence in patients
with amniotic fluid embolism and is
thought to be due to hypoxia and impaired oxygen delivery to the brain. The
possibility of amniotic fluid having a direct effect on the central nervous system
by either vascular obstruction or other
pathways remains unproven. As many as
85% of patients may suffer permanent
neurologic sequelae as a result of amniotic fluid embolism (5). Similar to DIC,
the onset of encephalopathy is variable
and it is sometimes the only presenting
clinical manifestation. Seizure activity is
present in 50% of patients and may occur
before, during, or shortly after encephalopathy develops. This seizure activity
may exacerbate brain injury, particularly
in the setting of hypoxia. Due to the rapid
progression of hypoxia and high incidence of seizures, encephalopathy remains one of the most common causes of
morbidity in survivors of amniotic fluid
embolism.In most cases, amniotic fluid
embolism syndrome presents with an
abrupt and fulminant course of the clinical manifestations described here. Recent observations have indicated, however, that there is a less severe
presentation of amniotic fluid embolism
with variable incidence of major symptoms and a milder clinical course with
much better survival than for those who
have the full syndrome (21, 34, 35). These
observations may expand the clinical criteria of amniotic fluid embolism in the
future and could result in a lower overall
mortality rate.
The clinical presentation of amniotic
fluid embolism is complex and has various
clinical manifestations that may or may not
be present depending on the patient. On
closer inspection, the clinical course seems
to have phases that are likely temporally
related to pathophysiologic changes that
will be reviewed in the next section (31).
When amniotic fluid embolism is severe,
obstructive and cardiogenic shock appears
to be dominant during the early phase of
disease, whereas the later phase seems to be
marked by cardiogenic, distributive, and, at
times, hemorrhagic shock. Hypoxia seems
to be severe through both early and later
phases of amniotic fluid embolism but perhaps for different reasons, which may also
correspond to changing pathologic processes over time. As discussed previously,
the reasons for development of DIC may
also vary. Complicating matters is the possibility that these phases may overlap, with
multiple types of shock, hypoxia, and coagulopathy occurring simultaneously.
Pathogenesis
The pathogenesis of the amniotic fluid
embolism syndrome is still unclear. Amniotic fluid embolism occurs when there
is a breach in the barrier between the
maternal circulation and amniotic fluid.
Mechanisms of introduction of amniotic
fluid from the amniotic sac into the maternal venous circulation have been proposed through the endocervical veins, at
a placental site, or at a site of uterine
trauma (36). The introduction of amniotic fluid may also result from placental
abruption and disruption of fetal membranes. Amniotic fluid is typically composed of desquamated skin cells, lanugo
and scalp hairs, prostaglandins, zinc coproporphyrin, and arachidonic acid metabolites. These components have been demonstrated in pregnant women without
clinical evidence of amniotic fluid embolism, in maternal sputum samples, and in
women who are not pregnant. Distinguishing between maternal and fetal cells
is technically difficult and may contribute
to the difficulty in obtaining a histologic
diagnosis in amniotic fluid embolism.
Historically, it was believed that amniotic
fluid debris found by aspirating a blood
sample from the distal port of a pulmonary artery catheter was pathognomonic
of the syndrome. Although not definitively diagnostic, this finding may increase the level of suspicion if the patient
exhibits signs and symptoms consistent
with amniotic fluid embolism. It is therefore unlikely that the mere presence of
amniotic fluid in the maternal circulation
is responsible for the development of the
characteristic clinical changes. Arachidonic acid metabolites have been implicated in the inflammatory response and
may be in part responsible for amniotic
fluid embolism, although supportive data
are lacking. Arachidonic acid metabolites
have been implicated in sepsis and anaphylaxis. The presence of these metabolites in amniotic fluid embolism suggests
a possible humoral mechanism. There
are several clinical findings frequently
seen in sepsis and anaphylaxis, such as
coagulopathy, DIC, left ventricular failure, and hemodynamic compromise, that
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are seen as well in amniotic fluid embolism. Humoral pathways invoking a
proinflammatory response with release of
cytokines and arachidonic acid metabolites in amniotic fluid embolism, anaphylaxis, and shock may be responsible for
the similar clinical presentation. This
complex inflammatory cascade with mediator release will lead to a systemic inflammatory response and the development of multiple-organ system failure.
Figure 3 illustrates possible immunologic
and humoral mechanisms in the development of the syndrome (31). There may
also be immunologic factors involved in
the pathogenesis of amniotic fluid embolism supported by observations that the
syndrome is more common in women
with a male fetus and occurs in more
than a third of women with a prior history of drug allergies (5). Immunologic
factors may be the cause of the significant
coagulopathy and bleeding resulting
from fulminant DIC in the majority of
patients.
Animal data and observational and hemodynamic data from women suggest that
there may be a biphasic physiology in the
development of the amniotic fluid embolism (20, 24). Hemodynamic data from animal studies demonstrate an early response
with acute cor pulmonale, pulmonary hypertension, and systemic hypotension.
Most likely, acute right heart failure results
from embolization of amniotic fluid and
fetal debris (squamous cells, mucin) with
occlusion and vasospasm of the maternal
pulmonary vasculature. These hemodynamic changes resolve rapidly within
15–30 mins in the animal model, and because of this resolution are not often detected in women with amniotic fluid em-
bolism. The clinical changes characteristic
of women with amniotic fluid embolism
encompass acute left heart failure with pulmonary edema and cardiogenic shock with
severe hemodynamic instability. These
clinical changes are consistent with hemodynamic data obtained with the pulmonary
artery catheter and by echocardiography.
They demonstrate elevated left heart filling
pressures with an increase in pulmonary
artery and pulmonary artery occlusion
pressures and diminished myocardial contractility reflected by a decrease in the left
ventricular stroke work index. These hemodynamic data support a humoral etiology
rather than a thromboembolic event.
Changes in right heart pressures, in particular central venous pressure, are variable
and may depend on the timing of the placement of the pulmonary artery catheter and
measurement of the pressure readings in
relation to the presenting symptoms. The
hemodynamic values obtained will be altered as well by resuscitative measures with
volume replacement, inotropic, and vasopressor support. The clinical findings of left
heart failure, coagulopathy, and cardiovascular instability may represent the second
pathophysiologic phase of this syndrome.
These findings may be directly influenced
by the early profound hypoxia demonstrated in the animal model that may subsequently result in multiple organ failure.
Diagnosis
Figure 3. Postulated mechanism for the pathogenesis of amniotic fluid embolism. DIC, disseminated
intravascular coagulation. Reproduced from Ref. 31 Copyright © 2004, with permission from Elsevier.
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The diagnosis of amniotic fluid embolism is a clinical diagnosis and essentially a
diagnosis of exclusion. It is made on the
basis of the clinical presentation of a
woman in labor or after delivery most commonly. The clinical diagnosis of amniotic
fluid embolism is strongly suspected in the
pregnant woman or the postpartum
woman who acutely, abruptly, and dramatically presents with profound shock and
cardiovascular collapse associated with severe respiratory distress. Other acute fulminant events such as pulmonary embolism,
anaphylaxis, sepsis, and myocardial infarction must be excluded. Although most patients initially present with cardiac and respiratory failure, there is a subset of
patients in whom severe hemorrhage with
DIC may be the first sign. Although most
patients present with a dramatic onset of
signs and symptoms, there may be early
subtle signs that indicate hypoxia and impending cardiopulmonary failure, such as
restlessness and alterations in mental status. The clinical diagnosis is made most
frequently in 65–70% of cases during labor
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
and much less frequently, in 11% of cases,
in the postpartum patient. There are reports as well that amniotic fluid embolism
may produce a less complex and less acute
constellation of symptoms (35). There have
been instances described when the woman
experienced early signs of DIC and respiratory failure but not to the degree and extent
of the more severe syndrome. Recovery
from this abridged form of amniotic fluid
embolism is good, and the diagnosis is
made by exclusion of other acute events
producing similar symptomatology.
There are no specific laboratory tests
that confirm the diagnosis of amniotic
fluid embolism, but some tests may support the diagnosis. Initial laboratory data
should include an arterial blood gas to
determine adequacy of ventilation and
the degree of hypoxemia. Other laboratory values such as electrolytes, calcium
and magnesium levels, complete blood
count including platelets, and a coagulation profile should be obtained after the
initial stabilization of the patient. As an
acute phase reactant, the white blood cell
count may be elevated. Depending on the
presence of DIC and the rate of associated
hemorrhage, the hemoglobin and hematocrit values will be diminished. Typical
laboratory manifestations of DIC with elevated prothrombin and thromboplastin
values and a decreased fibrinogen level
will be detected. Thrombocytopenia is a
rare finding. Radiographic findings are
not diagnostic. Patients with cardiogenic
and noncardiogenic pulmonary edema
will have radiographic evidence of pulmonary edema with interstitial and alveolar
infiltrates distributed bilaterally. Acute
left heart failure is not usually associated
with cardiomegaly, although the heart
size of the pregnant woman appears tends
to appear larger on the chest radiograph
because the heart is normally pushed upward and outward because of the enlarged uterus. This is particularly more
noticeable on a portable anterior posterior chest radiograph. A 12-lead electrocardiogram is necessary to look for signs
of ischemia and infarction. If there is a
suspicion of cardiac ischemia, creatine
phosphokinase isoenzymes and troponin
levels should be measured. The electrocardiogram may show tachycardia, ST
and T-wave abnormalities, or findings
consistent with right ventricular strain.
Cardiac arrhythmias or asystole can be
seen with severe cardiovascular collapse.
Transthoracic or transesophageal echocardiography may demonstrate acute left
heart failure with diminished left ventricCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
ular contractility. Porat et al. (27) demonstrated intracardiac thrombi in the
right atrium and in the right ventricular
outflow tract. Some investigators have
used an immunostaining technique of
the monoclonal TKH-2 antibodies in maternal serum and lung tissue. TKH-2 reacts with meconium and the mucin derived from amniotic fluid and stains the
lung tissue of women with amniotic fluid
embolism (6). Another method described
has been the measurement of zinc coproporphyrin, a component of amniotic
fluid found in the maternal serum, which
is elevated in patients with amniotic fluid
embolism (37). One study found the levels of tissue factor significantly higher in
amniotic fluid compared with maternal
plasma levels (10). The level of tissue
factor pathway inhibitor was lower in
plasma of pregnant women than in nonpregnant controls. This study may suggest that amniotic fluid in the maternal
venous circulation acts as a trigger for
intravascular coagulation. A number of
reports have described an increase in the
tryptase level, suggesting an association
with anaphylaxis (38, 39). Other investigators found normal levels of tryptase but
low levels of complement (7, 40). This
may suggest a role for complement activation in amniotic fluid embolism. The
practical utility of these laboratory assays
is limited and their presence has not been
validated in the diagnosis of amniotic
fluid embolism. The diagnosis is definitively confirmed postmortem by the presence of fetal squamous cells and other
elements of fetal debris in the pulmonary
vessels.
Management
Monitoring of the patient with suspected amniotic fluid embolism includes
continuous cardiac telemetry and respiratory monitoring with pulse oximetry or
with an end-tidal CO2 monitor. If the
patient has not yet delivered, a continuous fetal monitoring device should be
placed. Blood pressure monitoring is performed with frequent serial noninvasive
measurements or by insertion of an intraarterial catheter for continuous blood
pressure readings. Obtaining intravenous
access is paramount. Insertion of a central venous catheter or a pulmonary artery catheter may guide the hemodynamic management of this patient, but
insertion of the catheters should never
delay appropriate and expeditious treatment. There are no prophylactic measures to prevent the development of amniotic fluid embolism except for constant
vigilance of the parturient, especially if
she suddenly becomes restless and agitated and complains of dyspnea. One difficulty in the initial treatment of amniotic fluid embolism is the rapidity at
which signs and symptoms can occur
that should prompt the clinician to be
vigilant and ready to implement therapy
as needed. The time from delivery to the
onset of symptoms has ranged from 15 to
45 mins and the time from collapse to
death has been reported as 1–7 hrs.
The management of amniotic fluid embolism is supportive and focuses initially on
rapid maternal cardiopulmonary stabilization (Table 4). The majority of patients will
require intensive care unit admission after
initial stabilization. The most important
goal of therapy is to prevent additional hypoxia and subsequent end-organ failure. Oxygen is given immediately to prevent the
initial acute hypoxia seen in amniotic fluid
embolism and to prevent the subsequent
severe neurologic impairment seen in a significant number of survivors. Irrespective
of whether oxygen is delivered by face
mask, bag-valve mask, or endotracheal intubation, the immediate therapy is to deliver oxygen expeditiously. Fluid resuscitation is imperative to counteract
hypotension and hemodynamic instability.
Transthoracic or transesophageal echocardiography may guide fluid therapy with
evaluation of left ventricular filling (16).
For refractory hypotension, vasopressor
therapy will be required. Dopamine or norepinephrine may be ideal agents because of
the additional ␤-adrenergic effects, which
improve cardiac function in addition to the
␣-adrenergic vasoconstrictor effects. Ino-
Table 4. General supportive measures in the treatment of amniotic fluid embolism
1.
2.
3.
4.
5.
Treat
Treat
Treat
Treat
Treat
hypoxia with 100% oxygen.
hypotension by fluid resuscitation with isotonic solutions and vasopressors.
left ventricular diminished contractility with fluids and inotropic therapy.
DIC and coagulopathy with FFP, cryoprecipitate, fibrinogen, and factor replacement.
hemorrhage with RBC transfusions and thrombocytopenia with platelets.
DIC, disseminated intravascular coagulation; FFP, fresh frozen plasma; RBC, red blood cells.
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tropic support with dobutamine or milrinone may be needed for inotropic support.
DIC with hemorrhage is treated based on
the degree of hemorrhage with RBC transfusions and platelets, if thrombocytopenia
is present. Specific coagulation laboratory
abnormalities are treated with fresh frozen
plasma, cryoprecipitate, fibrinogen, and/or
factor replacement. Several newer therapies have been described in the treatment
of amniotic fluid embolism, although they
only have been reported anecdotally and in
very small case reports (Table 5) (41– 46).
In 65% of the cases of amniotic fluid
embolism, delivery has not yet occurred.
In these instances, immediate delivery of
the fetus is mandated to prevent further
hypoxic damage to the fetus and to facilitate cardiopulmonary resuscitative efforts. A perimortem Cesarean section is
initiated within several minutes, and
standard advanced cardiac life support
medications are given to restore maternal
circulation and to treat arrhythmias if
present. There should never be a delay in
the administration of advanced cardiac
life support medications because of the
fear of inducing uterine hypoperfusion or
fetal toxicity. The goal of drug therapy is
prompt restoration of normal maternal
hemodynamics in conjunction with delivery of the fetus within 3 to 4 mins after
the onset of asystole or a malignant arrhythmia (47). During cardiopulmonary
resuscitation and chest compressions and
before delivery, the uterus should be displaced to the left to avoid compression of
the aorta and the inferior cava that compromise maternal venous return to the
heart. The uterus can be displaced manually or by placing a wedge under the
woman’s right hip. Because of the association of coagulopathy with DIC and
uterine atony in amniotic fluid embolism, the clinician should be prepared to
treat the uterine atony with standard
medical and surgical resuscitative methTable 5. Newer strategies in the treatment of
amniotic fluid embolism
1. Intra-aortic balloon counterpulsation (41)
2. Extracorporeal membrane oxygenation (41)
3. Cardiopulmonary bypass (17)
4. Plasma exchange transfusions (42, 43)
5. Uterine artery embolization (40, 44)
6. Continuous hemofiltration (43)
7. Cell-salvage combined with blood filtration
(45)
8. Serum protease inhibitors (46)
9. Inhaled nitric oxide (46)
10. Inhaled prostacyclin (46)
11. High-dose corticosteroids (46)
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ods, including aggressive blood product
replacement, uterotonic medications,
and a hysterectomy if the bleeding cannot
be controlled medically. If the patient
survives, multiple organ systems may be
affected and the clinician must be prepared to manage the sequelae to reduce
the significant morbidity associated with
this syndrome (Table 6).
Prognosis
The prognosis and mortality of amniotic fluid embolism have improved significantly with early recognition of this syndrome and prompt and early resuscitative
measures. Specialized courses in resuscitation, such as Advanced Cardiac Life
Support, Acute Life Support in Obstetrics, and Managing Obstetrical Emergencies and Trauma, may improve mortality
by standardization of care. The decrease
in the mortality rate results solely from
early diagnosis and prompt treatment
rather than prevention of the syndrome,
since the cause is unknown. Those
women who survive long enough to be
transferred to the ICU have a better
chance of survival. In some cases, death is
inevitable despite early and appropriate
management. Although mortality rates
have declined, morbidity remains high
with severe sequelae, particularly neurologic impairment. Neonatal survival is reported at 70%. There are no data to support reoccurrence of the syndrome with
subsequent pregnancies if the woman
survives. Amniotic fluid embolism remains largely unpreventable and unpredictable although our efforts at early diagnosis and resuscitation have
dramatically improved the devastation of
this syndrome. Although there are many
new developments with respect to our
knowledge of the disease, amniotic fluid
embolism continues to be a catastrophic
Table 6. Sequelae of amniotic fluid embolism
1. Cardiac failure with left ventricular
impairment, cardiogenic pulmonary edema,
arrhythmias, or myocardial ischemia and
infarction
2. Respiratory failure with noncardiogenic
pulmonary edema and refractory
bronchospasm
3. Neurologic compromise with seizures and
altered mentation
4. Acute oliguric or nonoliguric renal failure
5. Hematologic compromise with disseminated
intravascular coagulation, hemorrhage, or
thromboses
illness requiring a high index of suspicion, a multidisciplinary approach, and
rapid resuscitation efforts in order to
have a desirable clinical outcome.
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