Amniotic fluid embolism
Synonyms and keywords: AFE; Amnioembolism; Pulmonary amnioembolism.

# Overview
Amniotic fluid embolism (AFE) is a rare and incompletely understood obstetric emergency in which amniotic fluid, fetal cells, hair or other debris enters the mother's blood stream via the placental bed of the uterus and triggers an allergic reaction. This reaction then results in cardiorespiratory (heart and lung) collapse and coagulopathy. The condition is so rare (less than 1 in 20,000 deliveries) that most doctors will never encounter it in their professional careers, and as a result the exact process is poorly understood. However, it is believed that once the fluid and fetal cells enter the maternal pulmonary circulation a two-phase process occurs. First phase: The patient experiences acute shortness of breath and hypertension. This rapidly progresses to cardiac arrest as the chambers of the heart fail to dilate and there is a reduction of oxygen to the heart and lungs. Not long after this stage the patient will lapse into a coma. 50% die within the first hour of symptoms. Second phase: Although many women do not survive beyond the first stage, about 40 per cent of the initial survivors will pass onto the second phase. This is known as the hemorrhagic phase and may be accompanied by severe shivering, coughing, vomiting and the sensation of a bad taste in the mouth. This is also accompanied by excessive bleeding as the blood loses its ability to clot. Collapse of the cardiovascular system leads to fetal distress and death unless the child is delivered swiftly.

# Historical Perspective
- In 1926, Meyer was first who described the underlying pathophysiology of amniotic fluid embolism (AFE).
- In 1949, Shotton and Taylor described the contemporary symptoms of sudden and profound shock, dyspnea, cyanosis, and pulmonary edema as the associated symptoms.

# Pathophysiology

## Pathogenesis:
- The exact pathophisiology of AFE is unknown. Abnormal maternal response to fetal tissue exposure during vaginal delivery, cesarean, second trimester of pregnancy or even post delivery could be the initial step resulting AFE.
- It has been suggested the main reason of AFE is immune response not embolic process.
- Amniotic fluid caused intravascular coagulation by having procoagulant products such as platelet-activating factor, cytokines, bradykinin, and thromboxane. Also, Complement system activation might play a role in causing AFE.

## Hemodynamic Consequences
- The most common complication and presentation of amniotic fluid embolism is in the pulmonary vessels.
- Hemodynamic complications and the nature of the clinical manifestations of a pulmonary amniotic fluid embolism depends on a number of factors:
The size of the embolus and the degree to which it occludes the vascular tree and its subsequent branches
The presence of any preexisting cardiopulmonary conditions
The role of chemical vasoconstriction as it is insinuated by platelets releasing serotonin and thromboxane in addition to other vasoconstrictors
- The size of the embolus and the degree to which it occludes the vascular tree and its subsequent branches
- The presence of any preexisting cardiopulmonary conditions
- The role of chemical vasoconstriction as it is insinuated by platelets releasing serotonin and thromboxane in addition to other vasoconstrictors
- Pulmonary amniotic fluid embolism results in the elevation of the pulmonary vessel resistance as a consequence of not only mechanical obstruction of the capillary by the embolism, but also due to pulmonary vasoconstriction.  Pulmonary vasoconstriction can be either biochemically mediated, hypoxia induced, or reflex-induced.
- Several mediators are involved the pulmonary vasoconstriction that occurs in the setting of acute pulmonary amniotic fluid embolism, such as:
Thromboxane A2 (end product of arachidonic acid metabolism)
Serotonin (vasoconstrictor in the pulmonary circulation and vasodilator in the systemic circulation)
Endothelin 1
Prostaglandin F2
Thrombin
Histamine
- Thromboxane A2 (end product of arachidonic acid metabolism)
- Serotonin (vasoconstrictor in the pulmonary circulation and vasodilator in the systemic circulation)
- Endothelin 1
- Prostaglandin F2
- Thrombin
- Histamine
- The embolus may start local inflammatory response which will lead to:
Release of cytokines serotonin and thromboxane A2 that are mainly produced by activated platelets
The vascular wall and pulmonary neuroendocrine cells might also be the source of some vasoconstrictors
- Release of cytokines serotonin and thromboxane A2 that are mainly produced by activated platelets
- The vascular wall and pulmonary neuroendocrine cells might also be the source of some vasoconstrictors
- Prostacyclin is a vasodilator produced by the endothelial cells in response to the hemodynamic changes induced by the acute pulmonary amniotic fluid embolism.
- When pulmonary vascular resistance occurs following an acute pulmonary amniotic fluid embolism, the rapid increase in the right ventricular afterload might lead to the dilatation of the right ventricular wall and subsequent right heart failure. In addition, the elevated pulmonary vascular resistance causes a decrease in the left ventricular preload and consequently leads to systemic hypotension. In patients with underlying cardiopulmonary disease, the cardiac output suffers substantial deterioration in overall output as compared to otherwise healthy individuals.
- Right heart failure, as well as systemic hypotension, can attenuate coronary perfusion and contribute to subsequent coronary ischemia.

# Causes
It is mostly agreed that this condition results from amniotic fluid entering the uterine veins and in order for this to occur there are three prerequisites:
- Ruptured membranes (a term used to define the rupture of the amniotic sac)
- Ruptured uterine or cervical veins
- A pressure gradient from uterus to vein
Although exposure to fetal tissue is common and thus finding fetal tissue within the maternal circulation is not significant, in a small percentage of women this exposure leads to a complex chain of events resulting in collapse and death.
- Drugs causing amniotic fluid embolism
- Dinoprostone

# Differentiating Amniotic fluid embolism from other Diseases
- Anaphylaxis
- Septic shock
- Air embolism
- Cholestrole embolism

# Epidemiology and Demographics
The exact incidence of AFE is unknown but it  has been reported between 1 in 8000 and 1 in 80,000 deliveries.
The mortality rate is between 13-26%. If it happens during pregnancy the mortality death in neonate is around 10%.

## Age
- Although older maternal age is considering a risk factor, but AFE can happen in all pregnant ladies in all ages.

## Gender
AFE happens in female.

## Race
- There is no racial predilection for AFE.

# Risk Factors
Maternal risk factors: 
- Multiparity
- intense contraction during labor
- History of eclampsia
Fetal risk factors:
- Male baby

# Natural History, Complications and Prognosis
The overal prognosis of AFE is very poor. Early diagnosis and resuscitative measures can save the patient's life. Neurological impairment, renal failure, respiratory and cardiac failure are the complications of AFE.

# Diagnosis

## Diagnostic Criteria
AFE is a diagnosis of exclusion. Classic triad of sudden hypoxia, hypotension, and subsequent coagulopathy in mother especially after labor could be AFE. 

## Symptoms
- Dyspnea
- cough
- Bleeding
- Confusion
- Seizure 

## Physical Examination
- Hypoxia
- Hypotension
- Coagulopathy
- encephalopathy
- Uterine atony 

## Laboratory Findings
- There are no specific laboratory test for diagnosing AFE. How ever there are some changes in some lab tests which include:
- Arterial blood gas: hypoxemic changes like respiratory acidosis.
- CBC: Anemia, Prothrombin time prolongation.
- Decrease in complement system.
- Increased serum tryptase. 

## Imaging Findings
- There are no specific findings associated with AFE.

## Other Diagnostic Studies
Transesophageal echocardiography:  right ventricular dilation due to pulmonary vasoconstriction 

# Treatment
The important key in treating AFE is diagnosing it as soon as possible.

## Medical Therapy 
- Keep patient's vital sign stable by fluid resuscitation, giving oxygen and transfusion of packed red blood cells if needed.
- Platelet transfusion if platelets are <20,000/L without any bleeding, or platelets are 20,000-50,000/L with bleeding, transfuse platelets at 1-3 U/10 kg/day.
- If any coagulopathy is present, it can be treated with activated recombinant factor VIIa. Acticated recombinant factor VIIa can be used with a dosage of 20-120 mcg/kg in order to prevent serious bleedings associated with amniotic fluid embolism.
- If coagulopathy is present,the first line treatment is to start with FFP for a prolonged aPTT, cryoprecipitate for lower than 100 mg/dL fibrinogen level, and platelet transfusion if thrombocytopenia is present.

## Surgery
In case of severe persistent uterine hemorrhage, hysterectomy should be done.

## Prevention
- Avoid any trauma to the uterus during labor.