Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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. S279 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 S281 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. S282 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. S283 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) S284 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. REFERENCES 1. Meyer JR: Embolia pulmonar amnio caseosa. Bras Med 1926; 2:301–303 2. Steiner PE, Lushbaugh C: Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. JAMA 1941; 117:1245–1254, 1340 –1345 3. Tuffnell DJ: Amniotic fluid embolism. Curr Opin Obstet Gynecol 2003; 15:119 –122 4. Gilbert WM, Danielsen B: Amniotic fluid embolism: Decreased mortality in a populationbased study. Obstet Gynecol 1999; 93: 973–977 5. Clark SL, Hankins G, Dudley DA, et al: Amniotic fluid embolism: analysis of the national registry. Am J Obstet Gynecol 1995; 172:1158 –1167 6. Oi H, Kobayashi H, Hirashima Y, et al: Serological and immunohistochemical diagnosis of amniotic fluid embolism. Semin Thromb Hemost 1998; 24:479 – 484 7. Benson MD, Kobayashi H, Silver RK, et al: Immunologic studies in presumed amniotic fluid embolism. Obstet Gynecol 2001; 97: 510 –514 8. Martin RW: Amniotic fluid embolism. Clin Obstet Gynecol 1996; 39:101–106 9. Benson MD, Lindberg RE: Amniotic fluid embolism, anaphylaxis, and tryptase. Am J Obstet Gynecol 1996; 175:737 10. Uszynski M, Zekanowska E, Uszynski W, et al: Tissue factor and tissue factor pathway inhibitor (TFPI) in amniotic fluid and blood plasma: Implications for the mechanism of amniotic fluid embolism. Eur J Obstet Gynecol Reprod Biol 2001; 95:163–166 11. Lockwood CJ, Bach R, Guha A, et al: Amniotic fluid contains tissue factor, a potent initiator of coagulation. Am J Obstet Gynecol 1991; 165:1335–1341 12. Hassart TH, Essed GG: Amniotic fluid embolism after transabdominal amniocentesis. Eur J Obstet Gynecol Reprod Biol 1983; 16: 25–30 13. Cromley MG, Taylor PJ, Cumming DC: Probable amniotic fluid embolism after firsttrimester termination. A case report. J Reprod Med 1983; 28:209 –211 14. Meier PR, Bowes WA Jr: Amniotic fluid embolus-like syndrome presenting in the second trimester of pregnancy. Obstet Gynecol 1983; 61(3 Suppl):31S–34S 15. Price TM, Baker VV, Cefalo RC: Amniotic fluid embolism. Three case reports with a review of the literature. Obstet Gynecol Surv 1985; 40:462– 465 16. James CF, Feinglass NG, Menke DM, et al: Massive amniotic fluid embolism: Diagnosis aided by emergency transesophageal echo- Crit Care Med 2005 Vol. 33, No. 10 (Suppl.) 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. cardiography. Int J Obstet Anesth 2004; 13: 279 –283 Stanten RD, Iverson LI, Daugharty TM, et al: Amniotic fluid embolism causing catastrophic pulmonary vasoconstriction: Diagnosis by transesophageal echocardiogram and treatment by cardiopulmonary bypass. Obstet Gynecol 2003; 102:496 – 498 Koegler A, Sauder P, Marolf A, et al: Amniotic fluid embolism: A case with non-cardiogenic pulmonary edema. Intensive Care Med 1994; 20:45– 46 van Haeften TW, Strack van Schijndel RJ, Thijs LG: Severe lung damage after amniotic fluid embolism: A case with haemodynamic measurements. Netherlands J Med 1989; 35: 317–320 Hankins GD, Snyder RR, Clark SL, et al: Acute hemodynamic and respiratory effects of amniotic fluid in the pregnant goat model. Am J Obstet Gynecol 1993; 168:1113–1130 Clark SL: New concepts of amniotic fluid embolism: A review. Obstet Gynecol Surv 1990; 45:360 –368 Locksmith GJ: Amniotic fluid embolism. Obstet Gynecol Clin North Am 1999; 26: 435– 444 Fletcher SJ, Parr M: Amniotic fluid embolism: A case report and review. Resuscitation 2000; 43:141–146 Clark SL, Montz FJ, Phelan JP: Hemodynamic alterations associated with amniotic fluid embolism: A reappraisal. Am J Obstet Gynecol 1985; 151:617– 621 Clark SL: Amniotic fluid embolism. Clin Perinatol 1986; 13:801– 811 Dib N, Bajwa T: Amniotic fluid embolism causing severe left ventricular dysfunction and death: Case report and review of the literature. Cathet Cardiovasc Diagn 1996; 39:177–180 Crit Care Med 2005 Vol. 33, No. 10 (Suppl.) 27. Porat S, Leibowitz D, Milwidsky A, et al: Transient intracardiac thrombi in amniotic fluid embolism. Br J Obstet Gynaecol 2004; 111:506 –510 28. Girard P, Mal H, Laine JF, et al: Left heart failure in amniotic fluid embolism. Anesthesiology 1986; 64:262–265 29. Vanmaele L, Noppen M, Vincken W, et al: Transient left heart failure in amniotic fluid embolism. Intensive Care Med 1990; 16: 269 –271 30. Shechtman M, Ziser A, Markovits R, et al: Amniotic fluid embolism: Early findings of transesophageal echocardiography. Anesth Analg 1999; 89:1456 31. Aurangzeb I, George L, Raoof S: Amniotic fluid embolism. Crit Care Clin 2004; 20: 643– 650 32. Peterson EP, Taylor HB: Amniotic fluid embolism. An analysis of 40 cases. Obstet Gynecol 1970; 35:787 33. Beller FK: Disseminated intravascular coagulation consumption coagulopathy in obstetrics. Obstet Gynecol Annu 1974; 3:267 34. Kretzschmar M, Zahm DM, Remmler K, et al: Pathophysiological and therapeutic aspects of amniotic fluid embolism (anaphylactoid syndrome of pregnancy): Case report with lethal outcome and overview. Anaesthesist 2003; 52:419 – 426 35. Benson MD: Nonfatal amniotic fluid embolism. Three possible cases and a new clinical definition. Arch Fam Med 1993; 2:989 –994 36. Courtney LD: Amniotic fluid embolism. Obstet Gynecol Surv 1974; 29:169 –177 37. Kanayama N, Yamazaki T, Narusc H, et al: Determining zinc coproporphyrin in maternal plasma—A new method for diagnosing amniotic fluid embolism. Clin Chem 1992; 38:526 –529 38. Nishio H, Matsui K, Miyazaki T, et al: A fatal 39. 40. 41. 42. 43. 44. 45. 46. 47. case of amniotic fluid embolism with elevation of serum mast cell tryptase. Forens Sci Int 2002; 126:53–56 Farrar SC, Gherman RB: Serum tryptase in a woman with amniotic fluid embolism: A case report. J Reprod Med 2001; 46:926 –928 Dorne R, Pommier C, Emery JC, et al: Embolie de liquide amniotique: Evolution favorable après embolisation therapeutique des arteres uterines. Ann Fr Anesth Reanim 2002; 21:431– 435 Hsieh YY, Chang CC, Li PC, et al: Successful application of extracorporeal membrane oxygenation and intraaortic balloon counterpulsation as lifesaving therapy for a patient with amniotic fluid embolism. Am J Obstet Gynecol 2000; 183:496 – 497 Awad IT, Shorten GD: Amniotic fluid embolism and isolated coagulopathy: Atypical presentation of amniotic fluid embolism. Eur J Anaesthesiol 2001; 18:410 – 413 Kaneko Y, Ogihara T, Tajima H, et al: Continuous hemodiafiltration for disseminated intravascular coagulation and shock due to amniotic fluid embolism: Report of a dramatic response. Intern Med 2001; 40: 945–947 Goldszmidt E, Davies S: Two cases of hemorrhage secondary to amniotic fluid embolism managed with uterine artery embolisation. Can J Anaesth 2004; 50:917–921 Waters JH, Biscotti C, Potter PS, et al: Amniotic fluid removal during cell salvage in the cesarean section patient. Anesthesiology 2000; 92:1531–1536 Davies S: Amniotic fluid embolism: A review of the literature. Can J Anesth 2001; 48: 88 –98 Dildy GA, Clark SL: Cardiac arrest during pregnancy. Obstet Gynecol Clin North Am 1995; 22:303–314 S285