Amniotic fluid embolism (AFE) is a rare and unique obstetric complication characterized by sudden onset, rapid progression, and difficulty in prediction. It results from the entry of amniotic fluid and fetal antigens into the maternal circulation during labor or delivery. This leads to a cascade of pathophysiological changes, including pulmonary hypertension, hypoxemia, circulatory collapse, disseminated intravascular coagulation (DIC), and multi-organ failure. AFE is a significant cause of maternal mortality. The incidence and mortality rates of AFE vary widely across different regions. According to current literature, the incidence is estimated to be between 1.9 and 7.7 per 100,000 deliveries, with a case fatality rate ranging from 19% to 86%. With advancements in medical science and technology in recent years, the maternal mortality rate associated with AFE has shown a noticeable decline.
Etiology
Risk factors that may be associated with AFE include advanced maternal age in primiparas, multiparity, cervical laceration, polyhydramnios, multiple gestation, uterine hyperstimulation, precipitous labor, premature rupture of membranes, placenta previa, uterine rupture, cesarean section, and uterine curettage. The exact cause remains unknown, but several mechanisms are thought to be involved:
Elevated Intra-amniotic Pressure
During labor, especially in the second stage, intra-amniotic pressure can reach 100–175 mmHg. When this pressure exceeds venous pressure, amniotic fluid may be forced into ruptured microvessels and enter the maternal circulation.
Opening of Venous Sinuses
Injury to the cervix or uterus and rupture of venous sinuses during delivery may allow amniotic fluid to enter the maternal bloodstream through damaged vessels or placental sinuses.
Rupture of Fetal Membranes
Most cases of AFE occur after rupture of membranes, allowing amniotic fluid to enter the maternal circulation via small blood vessels in the decidua or cervix.
Pathophysiology
The entry of amniotic components into the maternal bloodstream is a prerequisite for the development of AFE.
Anaphylactoid Reaction
Fetal antigens present in amniotic fluid may trigger a type I hypersensitivity-like reaction. Mast cell degranulation and the abnormal release of arachidonic acid metabolites—including leukotrienes, prostaglandins, and thromboxanes—into the maternal circulation result in an anaphylactoid response.
Pulmonary Hypertension
Cellular elements in the amniotic fluid stimulate the release of vasoactive substances in the lungs, leading to reflex pulmonary vasospasm and pulmonary hypertension. This increases right ventricular load, causing acute right ventricular dilation and failure, reduces left atrial filling, and results in a significant drop in cardiac output. Consequently, peripheral circulatory collapse and hypotension occur, which may lead to sudden maternal death due to ischemia of vital organs.
Inflammatory Injury
The sudden systemic activation of inflammatory mediators in AFE resembles the systemic inflammatory response syndrome (SIRS).
Disseminated Intravascular Coagulation (DIC)
DIC is a hallmark of AFE and may be the only presenting symptom. Amniotic fluid contains large amounts of procoagulant substances similar to tissue thromboplastin, which trigger widespread microthrombosis and consumption of clotting factors and fibrinogen. The simultaneous release of inflammatory mediators and endogenous catecholamines activates the coagulation cascade, leading to DIC and contributing to maternal death.
Clinical Manifestations
AFE usually presents suddenly and is clinically severe. About 70% of cases occur during vaginal delivery, and 19% during cesarean section. Most events take place within two hours before delivery or up to 30 minutes postpartum. Rarely, AFE may occur during mid-trimester induction, amniocentesis, or trauma. Sudden cardiopulmonary collapse may lead to rapid maternal death.
Typical AFE
This is characterized by the classic triad of sudden hypoxemia, hypotension (disproportionate to blood loss), and coagulopathy.
Prodromal Symptoms
About 30%–40% of patients experience nonspecific symptoms such as dyspnea, chest pain, shortness of breath, chills, coughing, dizziness, fatigue, palpitations, nausea, vomiting, numbness, tingling, anxiety, agitation, or a sense of impending doom. Fetal heart decelerations or loss of variability may also be observed. Recognizing these symptoms is helpful for early identification.
Respiratory and Circulatory Collapse
Symptoms may include sudden dyspnea, cyanosis, convulsions, loss of consciousness or coma, weak and rapid pulse, sharp decline in blood pressure, and decreased oxygen saturation. Moist rales may be audible in the lung bases. Electrocardiogram may show signs of right heart strain, and in severe cases, ventricular fibrillation, pulseless ventricular tachycardia, or cardiac arrest may occur, leading to death within minutes.
Coagulopathy
There may be generalized bleeding tendencies, primarily uterine bleeding, as well as bleeding from surgical incisions, mucous membranes, needle puncture sites, hematuria, and gastrointestinal hemorrhage.
Multiple Organ Dysfunction
Multiple organs can be affected, particularly the central nervous system and kidneys, in addition to the heart and lungs.
Clinical presentations may follow a typical sequence or occur in an atypical pattern.
Atypical AFE
This form presents with subtle or milder symptoms and slower progression. Classic features such as acute respiratory or circulatory failure may be absent. When clinical signs cannot be explained by other causes, the possibility of AFE should be considered.
Diagnosis
The diagnosis of amniotic fluid embolism (AFE) is clinical in nature and requires all of the following five criteria to be met:
- Acute onset of hypotension or cardiac arrest.
- Acute hypoxemia, manifested as dyspnea, cyanosis, or respiratory arrest.
- Coagulopathy, supported by laboratory evidence of intravascular consumption of coagulation factors or hyperfibrinolysis, or clinically by severe hemorrhage without another identifiable cause.
- Onset of the above symptoms during labor, cesarean section, curettage, or shortly after delivery (most occur within 30 minutes after placental expulsion).
- The signs and symptoms described above cannot be explained by other medical conditions.
AFE should be considered in cases of unexplained acute cardiopulmonary failure in pregnant or postpartum patients, particularly if accompanied by one or more of the following: hypotension, arrhythmia, dyspnea, seizures, acute fetal distress, cardiac arrest, coagulopathy, hemorrhage, fatigue, numbness, restlessness, paresthesia, or other prodromal symptoms.
It is important to note that there is currently no internationally standardized diagnostic criteria or definitive laboratory test for AFE. The presence of fetal or amniotic components in maternal blood is no longer required for diagnosis. Even if amniotic components are found in blood or tissue samples, AFE cannot be diagnosed without supporting clinical features. Conversely, if amniotic components are not found but clinical signs strongly support the diagnosis, AFE should still be considered.
Differential Diagnosis
The diagnosis of AFE requires exclusion of other conditions that can cause cardiac, respiratory, or circulatory failure. These include pulmonary embolism, myocardial infarction, arrhythmia, peripartum cardiomyopathy, aortic dissection, cerebrovascular accident, drug-induced allergic reactions, transfusion reactions, anesthesia complications, uterine rupture, placental abruption, and eclampsia. It is also essential to distinguish AFE-related coagulopathy from coagulopathy due to massive postpartum hemorrhage.
Treatment
Once AFE is suspected, immediate resuscitation is critical. Timely intervention involving a multidisciplinary team—including obstetrics, anesthesiology, respiratory medicine, cardiology, and critical care—is essential for survival and prognosis. Treatment focuses on maintaining vital functions, supporting organ systems, and correcting coagulopathy and shock.
Respiratory Support
Airway patency should be maintained, and supportive measures should be implemented based on severity. Oxygenation may be enhanced using a face mask, noninvasive ventilation, endotracheal intubation, or extracorporeal membrane oxygenation (ECMO), depending on the patient's condition.
Circulatory Support
Since AFE initially presents with pulmonary hypertension and right heart failure leading to systemic circulatory collapse, continuous hemodynamic monitoring and interventions to maintain cardiac output and blood pressure are critical.
Hemodynamic Stabilization
Vasoactive and inotropic agents such as norepinephrine, dobutamine, and phosphodiesterase inhibitors may be used to support cardiac function and maintain blood pressure.
Reduction of Pulmonary Hypertension
Pulmonary vasodilators such as epoprostenol, sildenafil, iloprost, treprostinil, inhaled nitric oxide, or endothelin receptor antagonists (e.g., bosentan) may be considered. Other agents like papaverine, atropine, theophylline, and phentolamine have limited efficacy.
Volume Resuscitation
Regardless of the cause, effective circulating volume is insufficient in shock. Rapid fluid replacement and blood component therapy are required to correct hypovolemia. Central venous pressure should be monitored to assess cardiac preload and guide therapy.
Management of Cardiac Arrest
High-quality cardiopulmonary resuscitation (CPR) and advanced life support should be initiated immediately. Left uterine displacement should be applied to prevent inferior vena cava compression. After successful resuscitation, homeostasis should be maintained, infection prevented, neurologic protection reinforced, and vital organ functions supported.
Anti-allergic Therapy
The use of high-dose corticosteroids remains controversial, but early administration based on clinical experience may be beneficial. Common regimens include intravenous hydrocortisone 500–1,000 mg/day or methylprednisolone 80–160 mg/day. Dexamethasone 20 mg may also be given intravenously, followed by a continuous infusion of 20 mg.
Correction of Coagulopathy
Due to the high incidence of coagulopathy in AFE, early assessment and continuous monitoring of coagulation function are essential. Prompt initiation of massive transfusion protocols should include red blood cell suspension, large volumes of fresh frozen plasma, cryoprecipitate, fibrinogen, and platelets. Antifibrinolytic therapy may be applied. Heparin is not recommended.
Stabilization of Internal Environment and Prevention of Renal Failure
Metabolic acidosis and renal impairment often accompany circulatory and respiratory failure. Arterial blood gas and electrolyte levels should be monitored, and acid-base and electrolyte disturbances corrected promptly. Renal failure and infections should also be prevented.
Obstetric Management
If AFE occurs before fetal delivery, labor should be expedited via assisted vaginal delivery or emergency cesarean section while maternal resuscitation continues. If cardiac arrest occurs in pregnancies over 23 weeks, emergency cesarean delivery may improve outcomes.
Postpartum hemorrhage should be actively managed with uterotonic agents and, if necessary, surgical hemostasis. When bleeding is uncontrollable, timely hysterectomy may be required to save the patient's life.
Prevention
During artificial rupture of membranes, membrane stripping is not recommended to minimize injury to cervical blood vessels. Artificial rupture should not be performed during uterine contractions. During cesarean delivery, care should be taken to protect open uterine vessels before rupturing the amniotic sac. The indications for oxytocin should be well understood to avoid excessive uterine contractions. In cases of stillbirth or placental abruption, coagulation function should be closely monitored and managed appropriately. Additionally, trauma, uterine rupture, and cervical lacerations should be avoided to prevent complications.