Fat Embolism Syndrome

Fat embolism syndrome is a systemic reaction, most often after fracture of long bones or the pelvis, in which fat globules in the circulation cause respiratory, neurological and skin manifestations.

Embolization of fat occurs in up to 90% of long bone fractures, but the clinical syndrome affects only 1 to 5% of isolated long bone fractures and more of multiple or bilateral femoral fractures.

It follows reaming and nailing of the femur and tibia, joint replacement and spinal fusion, and rarely liposuction, sickle cell crisis, pancreatitis, burns and bone marrow transplantation.

Two mechanisms

• Mechanical: marrow fat enters torn veins and lodges in the pulmonary capillaries, crossing to the systemic circulation through a patent foramen ovale or by pulmonary shunts.
• Biochemical: lipase breaks fat into free fatty acids that injure the endothelium and cause inflammation, capillary leak and the respiratory distress, along with platelet aggregation.

Risk factors: closed fractures of the femur or tibia, young males, multiple fractures, delay in fixation and reaming of the intramedullary canal. Onset is 12 to 72 hours after injury (rarely after 5 days). Mortality is 5 to 15% in severe cases. Most survivors recover within days to weeks, including neurological function. Complications: acute respiratory distress syndrome, coma and seizures, retinal changes, thrombocytopenia and anemia.

• Respiratory: dyspnea, tachypnea, hypoxemia and crackles, from mild to acute respiratory distress syndrome (the earliest and most common feature)
• Neurological: confusion, drowsiness, agitation, focal deficit, seizures and coma, often out of proportion to the hypoxemia
• Petechial rash over the upper anterior chest, axillae, neck, conjunctivae and oral mucosa, appearing within 24 to 36 hours, lasting 5 to 7 days
• Fever, tachycardia, jaundice, renal changes, retinal exudates and hemorrhages
• Major criteria: petechiae, respiratory insufficiency and cerebral involvement. Minor criteria: fever, tachycardia, retinal changes, jaundice, renal changes, anemia, thrombocytopenia, raised erythrocyte sedimentation rate and fat globules in sputum
• Red flags: falling saturation after a fracture, new confusion, petechiae and unexplained fall in platelets

1. Clinical diagnosis using the major and minor criteria (usually at least two major criteria, or one major plus four minor criteria), after exclusion of other causes.
2. Arterial blood gas: hypoxemia and respiratory alkalosis early. PaO2 under 8 kPa on air is common.
3. Chest radiograph: may be normal initially, then bilateral patchy infiltrates ("snowstorm"). CT chest: ground-glass opacities and nodules.
4. MRI brain: multiple small hyperintense lesions on diffusion-weighted imaging in a "starfield" pattern, mainly in the white matter and watershed areas.
5. Blood tests: full blood count (falling platelets and hemoglobin), coagulation studies, creatinine, liver tests, calcium (low), lipase, and urine for fat globules (not specific).
6. Echocardiography: right ventricular strain and an intracardiac shunt if present (bubble study).
7. Fundoscopy for retinal exudates, hemorrhages and cotton wool spots.

Differentials: pulmonary embolism, acute respiratory distress syndrome of other cause, pneumonia, aspiration, sepsis, head injury, hemorrhagic shock and cerebral infarction.

Treatment is supportive, and early prevention matters most.

1. Prevention:
   • Early stabilization of long bone and pelvic fractures within 24 hours, since delay raises risk.
   • Careful nailing technique (venting of the canal, lavage and low reaming pressures).
   • Adequate resuscitation with balanced crystalloid and blood to preserve intravascular volume, and gentle handling of fractures.
   • Corticosteroid prophylaxis (methylprednisolone 1.5 mg/kg IV every 8 hours for 3 doses) has reduced hypoxemia in high-risk fracture patients in small trials. It is not universal because of infection risk and uncertain benefit.
2. Oxygen and ventilation: oxygen to maintain saturation over 94%, high-flow nasal oxygen or non-invasive ventilation, and early intubation for respiratory failure. Lung-protective ventilation with tidal volume 6 mL/kg ideal body weight, plateau pressure under 30 cmH2O and positive end-expiratory pressure 8 to 15 cmH2O.
3. Circulation: IV balanced crystalloid 500 mL boluses to maintain euvolemia, red cell transfusion for hemoglobin under 70 g/L (under 80 g/L with cardiac disease), and norepinephrine 0.05 to 0.5 micrograms/kg/min IV for hypotension. Avoid fluid overload.
4. Neurological care: treat seizures with lorazepam 4 mg IV, protect the airway, and keep head up 30 degrees with normal carbon dioxide, glucose and sodium.
5. Thromboprophylaxis: enoxaparin 40 mg SC once daily from 12 to 24 hours after bleeding is controlled (adjust in renal impairment). Therapeutic heparin does not treat fat embolism.
6. Refractory hypoxemia: prone positioning, neuromuscular blockade for early severe disease, inhaled nitric oxide 5 to 20 parts per million and extracorporeal membrane oxygenation.
7. Steroid treatment of established syndrome is not recommended, and albumin, heparin, alcohol and dextran have no proven role.
8. Definitive fracture management once the patient is stable, and early mobilization.

Follow-up: neurological and cognitive review at 6 weeks and 3 months, fracture healing and rehabilitation, and repeat imaging only if deficits persist. Counsel the patient on recovery over weeks to months.