Amniotic Fluid Embolism

Amniotic fluid embolism is a rare but severe complication of pregnancy. Entry of amniotic fluid into the maternal circulation was first described in 1926 by J R Meyer; however, the first recorded maternal death from amniotic fluid embolism (AFE) was not until 1941^[1].

Epidemiology

Incidence

• Although rare, it is the fifth leading cause of direct maternal mortality in the UK.
• The 2014 triennial report from Mothers and Babies: Reducing Risk through Audit and Confidential Enquiries across the UK (MBRRACE-UK) into maternal deaths in the UK and Ireland, showed a mortality rate of 0.33 per 100,000 pregnancies. 11 women were reported as having died of AFE in the four years between 2009-2012^[2].
• Internationally it has been found to be significantly associated with induction of labour and maternal age^[3]. Placenta praevia and placental abruption appear to increase the risk 3- to 10-fold. Analysis of UK data has shown an increased risk in older, ethnic-minority women and an association between postnatal AFE and caesarean delivery^[4].
• A prospective, national study of AFE is being undertaken by the United Kingdom Obstetric Surveillance System (UKOSS) and has currently found an estimated incidence in the UK of 1.7 cases per 100,000 maternities^[4].

Presentation

Initial pulmonary symptoms may be minor. Amniotic fluid embolises to the pulmonary circulation and the patient responds with the rapid development of a complex constellation of findings with sudden cardiovascular collapse, acute left ventricular failure with pulmonary oedema, disseminated intravascular coagulation and neurological impairment. These are due to a combination of mechanical blockage of blood vessels with amniotic fluid, an inflammatory reaction in the maternal circulation and an, as yet, poorly understood immunological reaction that has been compared to anaphylaxis or severe sepsis^[5].

The above may give a clue to diagnosis, before collapse and haemorrhage occur.

The classical scenario of AFE involves an older multiparous woman in advanced labour, who suddenly collapses.

It can also occur following:

• Termination of pregnancy.
• Amniocentesis.
• Placental abruption.
• Trauma.
• Caesarean section.
• Delivery - unexpectedly, up to 30 minutes after delivery.

There may be early nonspecific signs including dyspnoea, altered consciousness, sudden anxiety and restlessness and fetal bradycardia. Uterine hypertonus has also been reported^[6].

Diagnosis

AFE is a diagnosis of exclusion and is made clinically. It requires a high index of suspicion on clinical criteria, as above.

• Symptoms occurring during delivery with high likelihood of collapse and incipient disseminated intravascular coagulation.
• Clotting screen is often very abnormal, even before any observable haemorrhage, and will then exclude many other diagnoses.
• CXR may show pulmonary oedema, acute respiratory distress syndrome (ARDS), right atrial enlargement and a prominent pulmonary artery.
• ECG may show right heart strain and arrhythmia.
• Arterial blood gases will determine degree of hypoxaemia.
• Post-mortem will reveal fetal squamous cells and hair (lanugo) in the maternal pulmonary circulation.
• In the future, the measurement of complement, which may be activated following AFE, or the fetal antigen sialyl-Tn may help to diagnose the condition. However, no one test can confirm or disprove the diagnosis of AFE^[6].

Management

Although the diagnosis of AFE may be confused with other causes of collapse, effective resuscitation remains the fundamental treatment irrespective of the cause^[2].

Treatment is supportive, based on the ABCs of adult life support^[6]:

General^{[2, 7]}

• Resuscitation with high-flow oxygen; most patients will require endotracheal intubation.
• Fluids to maintain blood pressure.
• Consider pulmonary artery catheterisation in patients who are haemodynamically unstable.
• If the patient arrests, initiate cardiopulmonary resuscitation (CPR). If she does not respond to resuscitation, perform a perimortem caesarean delivery.
• In 2014 the Confidential Enquiry into Maternal Deaths recommended perimortem caesarean section within five minutes or as soon as possible after cardiac arrest. This is for the benefit of the woman and is fundamental to her resuscitation. It does not require moving her to an operating theatre^[5].
• The full protocol for a massive haemorrhage can be triggered at the time of the decision to proceed to perimortem caesarean section, using locally agreed words - eg, 'ongoing major obstetric haemorrhage. We need compatible blood now.'^[8]
• Signs and symptoms of adequate oxygen delivery and tissue perfusion should be continuously monitored to ensure the effectiveness of replacement and supportive therapy.

Pharmacological^[7]

• Inotropic support is likely to be required.
• Early treatment of coagulopathy should be considered in the presence of, for example, bleeding gums or haematuria.
• Management of coagulopathy should not be delayed^[8]:
  • Fresh frozen plasma (FFP) if activated partial thromboplastin time (aPTT) is  prolonged (more than 1.5 x normal).
  • Cryoprecipitate if fibrinogen level is less than 1 g/L.
  • Transfuse platelets if platelet counts are less than 50 x 10⁹/L.
  • Up to 1 litre of FFP and 10 units of cryoprecipitate (two packs) may be given empirically in the presence of massive haemorrhage, while awaiting the results of coagulation studies.
• Aggressive treatment of uterine atony medically with oxytocics, ergometrine and prostaglandins, and adjunctive techniques - eg, packing, tamponade or Rusch balloons.
• Cardiac output measurement may guide therapy, ensuring fluid overload does not occur.

Surgical

If bleeding cannot be controlled, early recourse to hysterectomy may be life-saving and should not be delayed until the woman is in extremis^[2]. Successful uterine artery embolisation has been described in two cases^[6].

Prognosis

The United Kingdom Amniotic Fluid Embolism Register was established to identify the incidence of the condition and to examine any differences or common factors between survivors and fatalities. It has been incorporated into the UK Obstetric Surveillance System (UKOSS)^[4]. All cases, whether the woman survives or not, should be reported to the register via UKOSS. If the mother collapses in a well-equipped hospital and receives immediate resuscitation, it is no longer the universally fatal condition of the past. The 2011 confidential enquiry report calculates a case fatality of 16.5%^[9]. There appears to have been a reduction in case fatality over a period of 30 years, which is thought to be in part due to improvements in care but also to better identification of women who survive AFE^[2].

Mortality and morbidity^[6]

Of those who die, 25% die within the first hour and most of the remainder by nine hours after presentation. Palliative care may be initiated concurrently with resuscitation. The aim of providing palliative care is both to relieve symptoms and distress in the woman and also to improve communication between the obstetric and intensivist teams and the woman and her relatives.

The majority of women will survive; however, most display some degree of neurological impairment. 7% have severe permanent neurological damage. Many will also have chronic sequelae of end-organ damage.

The perinatal death rate is between 20-25%. 50% of surviving neonates are neurologically intact; hypoxic ischaemic encephalopathy and cerebral palsy are common.