Amniotic Fluid Embolism

Amniotic fluid embolism can be rapidly fatal (within 1-4 hours) and the rates of mortality rates have been documented up to 80%. Amongst the survivors the incidence of severe and permanent neurologic injury is high.

The syndrome occurs unpredictably and is unpreventable.

Diagnosis is one of exclusion and so (premorbidly) is a clinical one, there being no specific test for the condition. Definitive diagnosis in non-survivors can only be can only be established at autopsy.

Essentially clinicians should suspect amniotic fluid embolism in the labour, delivery or immediate post partum setting, (within 48 hours) when there is sudden onset of unexplained shock and/or respiratory compromise.

Treatment is supportive. 

---

History

Amniotic fluid embolism was first reported in 1926 by JR Meyer in a single case report in Brazil Medico (Portuguese). However, it was not widely recognized until 1941 when an autopsy series of eight women who had died from sudden shock during labour reported squamous cells and mucin of foetal origin in the maternal pulmonary vasculature.

Epidemiology

Amniotic fluid embolism syndrome is rare.

Most studies indicate that the incidence rate is around 1-12 cases per 100,000 deliveries.

Pathophysiology

Amniotic fluid probably enters the maternal circulation through:

• The endocervical veins
• The placental insertion site
• A site of uterine trauma

At autopsy squamous cells and mucin of foetal origin are found in the maternal pulmonary vasculature as well as in the maternal vascular beds of the kidneys, liver, spleen, pancreas, and brain.

Once amniotic fluid reaches the maternal circulation, it can precipitate widespread systemic effects principally including:

1. Cardiogenic shock

The exact mechanism for this is unknown.

It may be a combination of right ventricular failure (amniotic fluid can cause occlusion and vasospasm of the maternal pulmonary vasculature, resulting in rapid development of pulmonary hypertension, acute cor pulmonale, and systemic hypotension) and left ventricular failure (due to hypoxic injury and/ or inflammatory mediated myocardial depression).           

2. Respiratory failure

Hypoxemia is a hallmark feature. The mechanism is unclear but may be a combination of:

• Severe ventilation/perfusion (V/Q) mismatching appears to be the primary cause of hypoxemia.
• An ARDS type reaction, i.e an inflammatory non-cardiogenic type of pulmonary oedema:
  • Evidence for damage to the endothelial-alveolar membrane and a capillary leak syndrome includes the high protein concentration in edema fluid and the presence of amniotic fluid debris in the sputum and alveolar spaces
• Cardiogenic pulmonary oedema (if LVF if severe enough)

3. Inflammatory / anaphylactoid type response

It seems unlikely that obstruction of the pulmonary vasculature is the lone cause of since amniotic fluid embolism as there can be a lag of some hours between the entry of amniotic fluid into the maternal circulation and the onset of the symptoms and signs of amniotic fluid embolism.

According to this hypothesis, foetal antigens enter the maternal circulation via the amniotic fluid.

The severity of the clinical manifestations may be related to the degree of immunologic stimulation or the balance of leukotrienes and other arachidonic acid metabolites in the amniotic fluid.

Risk Factors

A number of risk factors have been implicated with amniotic fluid embolism, including:

• Precipitous or tumultuous labour
• Advanced maternal age
• Cesarean and instrumental delivery
• Placenta previa and abruption
• Grand multiparity (≥ 5 live births or stillbirths)
• Cervical /uterine lacerations
• Foetal distress
• Eclampsia
• Medical induction of labour

These factors are possibly associated with amniotic fluid embolism but may not be the direct cause and none are reliably predictive.  

The syndrome is best considered unpredictable and unpreventable.

Clinical features

Diagnosis is one of exclusion and so premorbidly is a clinical diagnosis. Essentially clinicians should suspect amniotic fluid embolism in the labour, delivery or immediate post partum setting, (within 48 hours) when there is sudden onset of unexplained shock and/or respiratory compromise.

Definitive diagnosis in non-survivors can only be can only be established at autopsy.

The onset of the symptoms and signs of amniotic fluid embolism most commonly occurs during labor and delivery, or immediately postpartum. Rarely, it has been reported as late as 48 hours after cesarean delivery or postpartum

The principle clinical features include:

1. Hypotension due to cardiogenic shock
2. Hypoxemia and respiratory failure
3. Coma or seizures
4. Coagulopathy:
   • Disseminated intravascular coagulation
   • Severe haemorrhage may be the presenting sign.

Occasionally, there may be a “partial syndrome” with only respiratory impairment with disseminated intravascular coagulation without progression to the full syndrome.

Differential diagnosis

The differential diagnosis of amniotic fluid embolism is extensive and includes many other life threatening conditions and this makes the diagnosis challenging.

Differential diagnoses include:

1. Pulmonary embolism
2. Anaphylaxis
3. Septic shock
4. Eclampsia
5. Peripartum cardiomyopathy
6. Myocardial infarction.
7. Air embolism
8. Anaesthetic causes include high spinal anaesthesia and local anaesthetic toxicity.
9. Massive aspiration
10. Transfusion reaction

Investigations

The diagnosis of amniotic fluid embolism is essentially a clinical one of exclusion there being no specific test for the condition. Some serological tests are being investigated, including:

• TKH-2 (a fetal antigen that can also be observed in maternal lung samples)
• An insulin-like growth factor binding protein-1

However, these methods have not been fully validated and cannot be recommended for routine clinical practice at this stage.

Investigations therefore are directed at excluding other causes, as well as assessing the degree of severity and to help guide management decisions

The following should be considered:

1. Blood tests:
   • FBE
   • U&Es/ glucose
   • LFTs
   • Coagulation profile:
     • Disseminated intravascular coagulation is diagnosed by a rapid decline in platelet count, prolonged clotting times, the presence of fibrin degradation products in the plasma and low levels of coagulation inhibitors (such as anti-thrombin III) and low levels of fibrinogen.
   • ABGs/ VBGs/ lactate level
2. 12 lead ECG
3. CXR

Management

There is no specific treatment for amniotic fluid embolism and so treatment is supportive.

The principle goals of therapy will be:

• Correction of hypoxemia/ support of ventilation.
• Support of the circulation
• Urgent delivery/ cesarean section in women who have not delivered.

In general terms, management will consist of:

1. Immediate attention to ABC issues: Maintenance of maternal oxygenation is vital.
   • 100% oxygen
   • Intubation and ventilation
   • IV fluid resuscitation as required
2. Establish monitoring:
   • Arterial line
   • CVC
   • IDC
   • Continuous ECG monitoring.
3. Inotropes:
   • Vasopressors (noradrenaline) as required.
4. Seizures:
   • IV benzodiazepines, as usual
5. Correct coagulopathy:
   • Transfusion with blood products such as platelets and fresh frozen plasma and cryoprecipiate if there is a low fibrinogen
6. Treat haemorrhage as required:
   • Transfusion
   • Hysterectomy may be required for uterine atony
7. Delivery of baby:
   • When amniotic fluid embolism occurs intrapartum, the need for immediate delivery must be determined.
   • The decision is made on a case-by-case basis, but factors that favor urgent delivery include:
     • Fetal distress
     • Rapid and progressive deterioration of the mother’s condition.
     • Obstetric opinion that delivery of the fetus may facilitate maternal resuscitative efforts.
   • Operative vaginal delivery may be reasonable if the cervix is fully dilated and the fetal head has descended to a station of at least +2/5. Otherwise, an emergency cesarean delivery is indicated.

Disposition

If amniotic fluid embolism is suspected there must be immediate referral to

• Obstetric Unit
• Anaesthetic Unit
• ICU
• Paediatric Unit (if child not delivered)

Prognosis

In Australia and New Zealand amniotic fluid embolism is the leading cause of direct maternal morality (McDonnell, 2015).

Previous studies suggest mortality rates of up to 80%, but recent estimates have suggested a fatality rate of 13-26%. ⁴ A recent Australia-New Zealand population-based study reported a 15% fatality rate.

References

History

• Meyer JR. Embolia pulmonar amnio caseosa. Brasil-Medico 1926; 40: 301–303
• Steiner PE, Lushbaugh CC. Landmark article, Oct. 1941: Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. By Paul E. Steiner and C. C. Lushbaugh. JAMA. 1986 Apr 25;255(16):2187-203.

FOAMed

• Nickson C. Amniotic Fluid Embolism (AFE). CCC

Publications

• Benson MD. Amniotic fluid embolism: the known and not known. Obstet Med. 2014 Mar;7(1):17-21.
• Rafael A, Benson MD. Amniotic fluid embolism: Then and now. Obstet Med. 2014 Mar;7(1):34-6. 
• McDonnell, N., Knight, M., Peek, M.J. et al. Amniotic fluid embolism: an Australian-New Zealand population-based study. BMC Pregnancy Childbirth 15, 352 (2015).
• Kaur K, Bhardwaj M, Kumar P, Singhal S, Singh T, Hooda S. Amniotic fluid embolism. J Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):153-9.