Fat Embolism Syndrome

Last Updated on March 17, 2025

Fat embolism syndrome occurs due to refers to the passage of fat globules in the lung parenchyma and peripheral circulation. and causing serious consequences resulting in a distinct pattern of clinical symptoms and signs.

It is important to differentiate between fat emboli, fat embolism, and fat embolism syndrome.

Fat Emboli refers to the fat droplets that get into circulation and travel along.

Fat emboli occur in almost all patients the patients with long-bone fractures, but only few develop fat embolism syndrome (FES). Here we review the FES literature under different subheadings.

Fat embolism is the process by which fat emboli get in to the bloodstream to lodge within the vessel.

Fat embolism syndrome [FES]is the clinical serious manifestation of the fat embolism which has potential to cause multi-system dysfunction, especially in lungs and brain.

Fat embolism syndrome is a occurs when embolic fat macroglobules [large size globules, not microscopic] pass into the small vessels of the lung and other sites leading to endothelial damage, respiratory distress, cerebral dysfunction and other symptoms.

Fat embolism occurs in 90% of all trauma patients. Fat embolism syndrome accounts for only 2-5% of patients who have long-bone fractures. 

Thus most of the cases of fat embolism are asymptomatic [That means these cases do not progress to full-fledged fat embolism syndrome.

Asymptomatic fat embolism to the pulmonary circulation almost always occurs with major trauma, including elective surgical procedures such as intramedullary nailing of long bones.

Timely intervention in cases with fat embolism syndrome is life-saving which otherwise is associated with high mortality rate.

An overall mortality of 5-15% has been described as fat embolism syndrome.

Pathophysiology

The exact mechanism of fat embolism and resultant fat embolism syndrome is not clearly understood.

Mechanical and biochemical causes have been proposed.

The fat emboli may occur either by direct entry of fat globules from broken adipose tissue or bone marrow into the bloodstream in areas of trauma.

It is thought that the release of fat emboli leads to occlusion of the small vessels which triggers an inflammatory response leading to skin, lung and neural problems.

It is usually the initial manifestation typically appearing within 24 hours after the injury. T

The chemical theory states that Injury to the pulmonary capillary endothelium by free fatty acids occurs. These are formed by hydrolyzation of fats by that were hydrolyzed by lipoprotein lipase. These free fatty acids release local toxic mediators.

Cerebral and renal effects are caused by fat emboli that pass to the systemic circulation. The fat emboli are thought to pass to systemic circulation from pulmonary by patent foramen ovale which is seen in 20-30% of the normal population.

In the brain, gross encephalopathy, localized cerebral edema, and white-matter changes may occur.

Causes of Fat Embolism Syndrome

Long bone fractures are the major cause of this condition. Fractures of ribs and pelvis are also responsible.

Trauma caused by surgeries such as intramedullary nailing of the long bones, hip or knee replacements or even liposuction may also cause to release the fat globules into the bloodstream.

Massive soft tissue injury, severe burns and bone marrow biopsy are other reasons.

Following non-traumatic settings have been reported to be associated with fat embolism –

• Fatty liver
• Acute pancreatitis
• Sickle cell crisis
• Burns
• Decompression sickness
• Parenteral lipid infusion

Clinical Presentation

There would be a history of trauma or other procedures or another relevant history.

The syndrome typically presents 24-72 hours after the initial injury. Patient presents with respiratory changes, neurological abnormalities, and petechial rash.

Respiratory changes are often the first clinical feature to present.

Most early symptoms are breathlessness and rapid breathing [tachypnoea]. The severity of these symptoms may vary from patient to patient.

There would be a finding of hypoxemia on examination.

In severe cases these progress to respiratory failure and acute respiratory distress syndrome-like condition.

More than half of the patients with FES caused by long bone fractures develop severe hypoxemia and respiratory insufficiency and require artificial ventilation.

Neurological features and skin features often appear after the development of respiratory distress.

Mild confusion and drowsiness are usual neural symptoms. Some may have severe seizures. Focal neurological deficits may occur and are hemiplegia, aphasia [inability to speak], and visual field disturbances etc.

The petechial rash is last to develop and is seen in about 60% case. This pin-point rash develops because emboli lodge in small dermal capillaries and cause extravasation of erythrocytes.

Petechial rashes are commonly seen in the conjunctiva, oral mucous membrane, and skin folds of the upper body, especially the neck and axilla.

Decreased urine output[oliguria], blood in urine[hematuria ] and failure of the kidneys to produce urine [anuria] are associated features.

Diagnostic criteria

The diagnosis of FES is mainly clinical. Gurd’s criteria for diagnosis relies on these findings.

If there are one major criterion and 4 minor ones present, the diagnosis of FES is probable.

Major criteria

• Respiratory insufficiency
• Cerebral involvement
• Petechial rash

Minor criteria

• Tachycardia or increased heart rate
• Fever (usually >39°C)
• Confusion
• Sustained pO₂ <8 kPa
• Sustained respiratory rate >35/minute, in spite of sedation
• Retinal changes – cotton wool exudates and small hemorrhages, occasionally fat globules seen in retinal vessels
• Jaundice
• Renal signs
• Thrombocytopenia [Decerase in platlet count]
• Anemia
• High ESR
• Fat macroglobulinemia [fat in blood]
• Diffuse alveolar infiltrates ‘snow storm appearance’ on chest x-ray

Differential Diagnoses

• Pulmonary Embolism
• Thrombotic Thrombocytopenic Purpura

Lab Studies

Following lab studies may guide the diagnosis of fat embolism syndrome

Routine Blood Examination

Thrombocytopenia [decreased platelet count], anemia, and hypofibrinogenemia are indicative of fat embolism syndrome. However, they are nonspecific.

• Decreased hematocrit
  • Occurs within 24-48 hours due to intra-alveolar hemorrhage.
• Elevated lipase levels [not specific and can occur in any bone trauma.]
• Decreased calcium

Cytological Examination

Examination of urine, blood, and sputum may detect fat globules that are either free or in macrophages. But this test has low sensitivity and a negative result does not exclude fat embolism.

Cytology of pulmonary capillary blood [obtained from a wedged pulmonary artery catheter] may reveal fat globules. This test is beneficial for early detection of the at-risk patients.

Arterial Blood Gas Examination

Blood gases will show low oxygen [hypoxia] and higher carbon dioxide levels [hypocapnia].

Shunt Fraction

Increase in alveolar-to-arterial oxygen tension difference, especially if it occurs within 24-48 hours of a sentinel event is strongly suggestive of the syndrome.

Imaging

Radiography

Serial chest radiographs reveal increasing diffuse bilateral pulmonary infiltrates within 24-48 hours of the onset of clinical findings.

Evenly distributed, fleck-like pulmonary shadows (snow storm appearance), increased pulmonary markings and dilatation of the right side of the heart are features suggestive of the condition.

Computed Tomography

CT shows parenchymal changes consistent with acute lung injury or acute respiratory distress syndrome. However, the findings depend on the burden of secondary lung injury.

If CT shows nodular or ground-glass opacities in the setting of trauma, it is suggestive of fat embolism.  

Transesophageal Echocardiography

Transesophageal echocardiography may show repeated showers of emboli but three is a lack of correlation with the actual development of fat embolism syndrome.

Other Studies

Nuclear ventilation-perfusion imaging of the lungs may be normal or may demonstrate subsegmental perfusion defects.

Bronchoalveolar lavage specimens have been evaluated in trauma patients and sickle-cell patients with acute chest syndrome, and the results have been mixed. At present its use is controversial.

Treatment of Fat Embolism

There is no specific medical therapy for fat embolism and fat embolism syndrome. The supportive treatment aims at compensating or countering physiological derangements which have occurred.

At risk patients [as in trauma] should be put on continuous pulse oximetry for early detection of desaturation. This allows prophylactic administration of oxygen and thereby decreasing the chances of hypoxic injury and systemic complications of fat embolism syndrome.

Prompt surgical stabilization of long bone fractures reduces the risk of the syndrome.

Prophylactic placement of inferior vena cava filters may help reduce the volume of fat that reaches the heart in at-risk patients but the risk of the surgery should be weight against benefits..

Prognosis

• The mortality rate from fat embolism syndrome is 5-15%
• Neural deficit and coma may last for days or weeks. Residual deficits like personality changes, memory loss and cognitive dysfunction may remain.
• Pulmonary residual diffusion capacity deficits may exist even after a year, the time by which other lung deficits resolve.

References

• Habashi NM, Andrews PL, Scalea TM. Therapeutic aspects of fat embolism syndrome. Injury. 2006 Oct. 37 Suppl 4:S68-73.
• Fabian TC. Unraveling the fat embolism syndrome. N Engl J Med. 1993 Sep 23. 329(13):961-3.
• White T, Petrisor BA, Bhandari M. Prevention of fat embolism syndrome. Injury. 2006 Oct. 37 Suppl 4:S59-67.
• Yeo SH, Chang HW, Sohn SI, et al; Pulmonary and cerebral fat embolism syndrome after total knee replacement. J Clin Med Res. 2013 Jun;5(3):239-42. doi: 10.4021/jocmr1251w. Epub 2013 Apr 23.
• Stein PD, Yaekoub AY, Matta F, et al; Fat embolism syndrome. Am J Med Sci. 2008 Dec;336(6):472-7.
• Robinson CM; Current concepts of respiratory insufficiency syndromes after fracture.; J Bone Joint Surg Br. 2001 Aug;83(6):781-91.