Fat embolism syndrome

The signs, symptoms, causes and treatment of fat embolism syndrome had come up in Question 29 from the second paper of 2006. The college answer to this question was unfairly brief. Fat embolism also comes up as the major differential in Question 16 from the first paper of 2017, where it is one of the possible explanations for a post-ORIF hypoxia in a middle-aged trauma patient. Later still, it has resurfaced as Question 16 from the second paper of 2018, where the college expected a rather large amount of detail. 

An attempt to expand on this topic is made here, with the expectation that the time-poor candidate will not squander their time in reading extensively on a topic which has only infrequently merited the examiner's attention. If for whatever reason the candidate has time to squander, there are several excellent sources in the literature:

• Jain et al, 2008
• Mellor et al, 2001
• Gupta et al, 2007 (seems authoritative, as everybody who has written anything since 2007 has extensively referenced this paper)

Pathophysiology of fat embolism syndrome

Mechanical theory:

• Fat cells in long bones are disrupted by fracture, surgery etc
• Fat droplets emerge from those cells
• The fat droplet enter torn veins near the bone, when intramedullary pressure is higher then venous pressure (eg. an arterial haematoma is forming, or an orthopedic surgeon is hammering a nail)
• Venous embolism of fat droplets to the lung occurs, where the big ones clog the pulmonary capillaries and cause hypoxia.
• Smaller droplets can penetrate into the arterial circulation via the lung capillaries and embolise systemically
• The characteristic petechial rash distribution (anterior axillary fold, face and the root of the neck)  develops because the fat droplets accumulate in the aortic arch before embolising to the non-dependent skin.
• Its a great theory, but it does not explain the 72-hour delay which is sometimes seen.

Biochemical theory

• Embolised fat is degraded by hydrolysis in plasma to free fatty acids.
• Free fatty acids have been show to cause ARDS and lung injury
• The time it take to hydrolyse fat could explain the delay in onset.
• Levels of FFAs are moderately elevated in trauma patients

Coagulation theory

• Tissue thromboplastin is released from marrow
• This activates Factor VII directly, and also activates complement.
• DIC then develops
• Moreover the activation of complement tends to create an increase in pulmonary permeability producing subsequent ARDS-like pulmonary transudate.

Risk of fat embolism

Conditions Associated with Fat Embolism
(from Jain et al, 2008 )

Traumatic	Unrelated to trauma
Long bone fractures Pelvic fractures Fractures of other marrow-containing bones Orthopaedic procedures Soft tissue injuries (e.g. chest compression with or without rib fractures) Burns Liposuction Bone marrow harvesting and transplant	Pancreatitis Diabetes mellitus Osteomyelitis and panniculitis Bone tumour lysis Steroid therapy Sickle cell haemoglobinopathies Alcoholic (fatty) liver disease Lipid infusion (TPN or propofol) Cyclosporine A solvent Lymphography Altitude sickness

• One long bone fracture: 1-3% chance
• Chance increases in proportion of number of fractures, and size of involved bones
• 33% with bilateral femoral fractures

Clinical features and diagnostic criteria for fat embolism

Symptoms of fat embolism

• Confusion is usually the earliest symptom (60%), but seizures and focal neurological signs have also been reported (all resolve completely)
• Dyspnoea
• Tachypnoea
• Haemoptysis
• Usually, with a latent period (say, some days after the manipulation of a fracture).

Signs of fat embolism

• Respiratory features are present in 95%: moist crepitations over all lung fields, hypoxia, cyanosis. ARDS-like picture develops
• Fat globules may be seen in the sputum!
• Petechial rash (in 30-60%) - alone, enough to make the diagnosis according to Schonfelds criteria.
• Fever
• Tachycardia
• Purtscher’s retinopathy: 
  • cotton wool exudates
  • macular oedema
  • macular haemorrhage
  • retinal haemorrhages
  • visible fat droplets on ophthalmoscopy
• Jaundice
• Renal impairment
• Anaesthetists often note a sudden drop in end-tidal CO₂ concentration during a stable steady state.

Diagnostic Criteria for  Fat Embolism

Gurd's Criteria Major criteria Axillary or subconjunctival petechiae Hypoxaemia PaO2 <60 mm Hg, FIO2=0.4 Central nervous system depression disproportionate to hypoxaemia Pulmonary oedema Minor criteria Tachycardia >110 bpm Pyrexia >38.5°C Emboli present in the retina on fundoscopy Fat globules present in urine A sudden inexplicable drop in haematocrit or platelet values Increasing ESR Fat globules present in the sputum

Lindeque's criteria Sustained PaO2 <8 kPa Sustained PCO2of >7.3 kPa or a pH <7.3 Sustained respiratory rate >35 breaths min-1 despite sedation Increased work of breathing: dyspnoea, accessory muscle use,tachycardia, and anxiety Schonfeld criteria Petechiae = 5 Chest X-ray changes (diffuse alveolar infiltrates)= 4 Hypoxaemia (PaO2 < 9.3 kPa) = 3 Fever (>38°C) = 1 Tachycardia (>120 beats min–1) = 1 Tachypnoea (>30 bpm) = 1 Confusion = 1 Cumulative score >5 required for diagnosis

Laboratory features of fat embolism syndrome

• Thrombocytopenia
• Anaemia (sudden decrease) -70% of patients
• High ESR
• Fat macroglobulinaemia
• Hypocalcemia (due to free fatty acids binding calcium)
• Elevated serum lipase
• DIC-like coagulopathy
• ABG: respiratory alkalosis with hypoxia and an unexplained shunt
• ECG: right heart strain, RBBB

Characteristic radiologic features of fat embolism syndrome

• CXR: florid embolism may develop into a "flocculent" patchy widespread opacities, "snowstorm appearance".
• CT chest: non specific; focal areas of ground glass opacification
• CT brain: diffuse white-matter petechial hemorrhages consistent with microvascular injury.
• TOE: may actually catch the passing of fatty globules within the heart, but afterwards - useless.

Management of fat embolism

• Preventative management
  • Venting of the medullary cavity during surgery, to prevent rises in intramedullary pressure
  • Albumin infusion in the operating theatre (binds fatty acids)
• Specific management not supported by very strong evidence:
  • Corticosteroids
  • Aspirin
  • Heparin infusion (which supposedly encourage lipase activity and discourages the formation of platelet aggregates).
  • N-acetylcysteine (based on rat studies only)
• Boring, non-specific treatment:
  • O₂ supplementation
  • Positive pressure ventilation
  • Correction of coagulopathy
  • Replacement of platelets
  • Correction of the source problem (i.e. reduction of fractures)

Alcohol intoxication seems to be somehow protective against fat embolism.