AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In 1862, Zenker first described this syndrome at autopsy. In 1873, von Bergmann clinically diagnosed fat embolism syndrome for the first time.

Pathophysiology

Two theories about the syndrome exist. First, the mechanical theory states that large fat droplets are released into the venous system. These droplets are deposited in the pulmonary capillary beds and travel through arteriovenous shunts to the brain. Microvascular lodging of droplets produces local ischemia and inflammation, with concomitant release of inflammatory mediators, platelet aggregation, and vasoactive amines. Second, the biochemical theory states that hormonal changes caused by trauma and/or sepsis induce systemic release of free fatty acids as chylomicrons. Acute-phase reactants, such as C-reactive proteins, cause chylomicrons to coalesce and create the physiologic reactions described above. The biochemical theory helps explain nontraumatic forms of fat embolism syndrome.

Frequency

United States

Frequency is estimated to be 3-4%. Fat embolism is a clinical diagnosis. Many patients are likely to have a missed diagnosis because of subclinical illness or confounding injury or illness.

Mortality/Morbidity

• The mortality rate is 10-20%.
• Patients with increased age, multiple underlying medical problems, and/or decreased physiologic reserves have worse outcomes than other patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Trauma to long bone or pelvis, including orthopedic procedures
• Parenteral lipid infusion
• Recent corticosteroid administration

Physical

Respiratory symptoms, signs or radiologic disease; cerebral signs without other etiologies; and petechial rash are the major criteria. A pulse that is over 110 beats/min, fever over 38.5ºC, retinal changes of fat globules or petechiae, renal dysfunction, jaundice, acute drop in hemoglobin and/or platelets, and elevated sedimentation rate are the minor criteria. One major and 4 minor criteria, plus fat microglobulinemia, must be present to formally diagnose fat embolism syndrome.

• Cardiopulmonary
• • Early persistent tachycardia may herald the onset of the syndrome.
  • Patients become tachypneic, dyspneic, and hypoxic due to ventilation-perfusion abnormalities 12-72 hours after injury.
  • Patients become febrile with high-spiking temperatures.
• Dermatologic
• • Alert clinicians may notice reddish-brown nonpalpable petechiae developing over the upper body, particularly in the axillae, within 24-36 hours of insult or injury. These petechiae occur in only 20-50% of patients and resolve quickly, but they are virtually diagnostic in the right clinical setting.
  • Subconjunctival and oral hemorrhages and petechiae also appear.
• Neurologic
• • Central nervous system dysfunction initially manifests as agitated delirium but may progress to stupor, seizures, or coma and frequently is unresponsive to correction of hypoxia.
  • Retinal hemorrhages with intra-arterial fat globules are visible upon funduscopic examination.

Causes

• Blunt trauma (associated with 90% of all cases)
• Acute pancreatitis
• Diabetes mellitus
• Burns
• Joint reconstruction
• Liposuction
• Cardiopulmonary bypass
• Decompression sickness
• Parenteral lipid infusion
• Sickle cell crisis
• Pathologic fractures

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Arterial blood gas: An otherwise unexplained increase in pulmonary shunt fraction alveolar-to-arterial oxygen tension difference, especially if it occurs within 24-48 hours of a sentinel event associated with fat embolism syndrome, is strongly suggestive of the syndrome.
• Hematocrit, platelet count, fibrinogen: Thrombocytopenia, anemia, and hypofibrinogenemia are indicative of fat embolism syndrome; however, they are nonspecific.
• Urine studies: Urinary fat stains are not felt to be sensitive or specific enough for diagnosing fat embolism or for detecting a risk of it.
• • Fat globules in the urine are common after trauma.
  • Preliminary investigations of the cytology of pulmonary capillary blood obtained from a wedged pulmonary artery catheter revealed fat globules in patients with FES and showed that this method may be beneficial in early detection of patients at risk.
  • In the future, genotyping for polymorphisms associated with increased susceptibility to inflammatory stimuli may help identify those at risk of fat embolism syndrome.
• Specific antibody therapy targeting inflammatory molecules has not been useful.

Imaging Studies

• Chest radiography: Serial radiographs reveal increasing diffuse bilateral pulmonary infiltrates within 24-48 hours of onset of clinical findings.
• Noncontrast head CT: Findings from head CT performed because of alterations in mental status may be normal or may reveal diffuse white-matter petechial hemorrhages consistent with microvascular injury.
• Nuclear medicine ventilation/perfusion imaging of the lungs: Performed for suspicion of pulmonary embolus, the findings from this scan may be normal or may demonstrate subsegmental perfusion defects.
• Helical chest CT for pulmonary embolism: As the embolic particles are lodged in the capillary beds, helical CT findings may be normal. Parenchymal changes consistent with lung contusion, acute lung injury, or adult respiratory distress syndrome may be evident. Nodular or ground glass opacities in the setting of trauma suggest fat embolism.
• MRI: Scant data exist regarding MRI findings in patients with this syndrome; however, in one small patient group, multiple, nonconfluent, hyperintense lesions were seen on proton-density– and T2-weighted images.
• Transcranial Doppler sonography: In a small case study, 5 patients with trauma were monitored with intracranial Doppler sonography, 2 during intraoperative nailing of long bone fractures.¹ Cerebral microembolic signals were detected as long as 4 days after injury.
• Transesophageal echocardiography (TEE): TEE may be of use in evaluating intraoperative release of marrow contents into the bloodstream during intramedullary reaming and nailing. The density of the echogenic material passing through the right side of the heart correlates with the degree of reduction in arterial oxygen saturation. Repeated showers of emboli have been noted to increase right heart and pulmonary artery pressures. Embolization of marrow contents through patent foramen ovale also has been noted. However, evidence of embolization by means of TEE is not correlated with the actual development of FES.

Procedures

• Bronchoalveolar lavage (BAL) with staining of alveolar macrophages for fat
• • BAL specimens have been evaluated in trauma patients and sickle cell patients with acute chest syndrome, and the results have been mixed.
  • Lipid inclusions commonly appear in patients with traumatic and nontraumatic respiratory failure; the standard cut-off of 5% fat-containing macrophages in the BAL studies results in a low specificity for the test. Some authors suggest increasing the cut-off to 30% to improve specificity.
  • Presently, using BAL to aid in the diagnosis or to predict the likelihood of fat embolism syndrome is controversial.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Medical care is supportive in nature and includes maintenance of adequate oxygenation and ventilation, stable hemodynamics, blood products as clinically indicated, hydration, prophylaxis of deep venous thrombosis and stress-related gastrointestinal bleeding, and nutrition.

Continuous pulse oximetry monitoring in at-risk patients (ie, those with long-bone fractures), may help in detecting desaturations early, allowing early oxygen therapy and possibly steroids, decreasing the chances of hypoxic insult and possible systemic complications of FES.

Surgical Care

Early stabilization of long bone fractures is recommended to minimize bone marrow embolization into the venous system. Rigid fixation within 24 hours has been shown to reduce the incidence of ARDS fivefold.

• Surgical technique, particularly of reaming or nailing the marrow, may help reduce the volume of fat embolization. However, a specific technique has not been identified.
• Prophylactic placement of inferior vena cava filters may help reduce the volume of fat reaching the heart.

Consultations

Depending on the mechanism of injury or insult, the specialists recommended to assist in management include orthopedists, neurologists/neurosurgeons, trauma care specialists, critical care specialists, pulmonologists, hematologists, and nutritionists.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Corticosteroids may be used in certain cases. Data does not support the use of one corticosteroid over another one. The best dosing protocol for corticosteroids in the treatment of fat embolism has not been established.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention:

• Corticosteroids as prophylaxis for fat embolism syndrome
• • Several studies have demonstrated varying results using corticosteroids, usually methylprednisolone, in patients identified as being at high risk for the syndrome.
  • Although the data appear compelling, the optimal timing, duration, and dose of steroids are undetermined.

  • Results of Randomized Controlled Trials of Corticosteroids in the Prevention of Fat Embolism Syndrome

    Dose	Model	Timing	Duration of Study	Effect on Disease Incidence
    30 mg/kg	Dog	Pre-event	60 min	None
    10 mg/kg q8h for 24 h	Human trauma	At admission	No data	Declining
    7.5 mg/kg q6h for 12 h or placebo	Human trauma	Within 12 h	2 d	Declining

Prognosis:

• The duration of FES is difficult to predict because FES is often subclinical or overshadowed by other illnesses or injuries.
• • Increased alveolar-to-arterial oxygen gradient and neurologic deficits, including coma, may last days or weeks.
  • Hematologic aberrations due to FES frequently are indistinguishable from other causes common in these patients.
• As in adult respiratory distress syndrome (ARDS), pulmonary sequelae usually resolve almost completely within 1 year.
• • Residual subclinical diffusion capacity deficits may exist.
  • Residual neurologic deficits may range from nonexistent to subtle personality changes to memory and cognitive dysfunction to long-term focal deficits.
  • Fat embolism syndrome alone has not yet been reported to cause global anoxic injury, but it may contribute with other cerebral insults.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Assuming altered mental status, fever, and hypoxia are due to fat embolism, the lack of a search for treatable or life-threatening disorders before making the diagnosis may lead to litigation if such a disorder is discovered later.
• • CT scan of the head is necessary to rule out intracranial pathology.
  • A careful search for infectious agents and possibly the institution of empiric antibiotics are necessary until an infectious source is ruled out.
  • Judicious use of crystalloids, colloids, and diuretics is necessary; volume depletion may precipitate shock and organ dysfunction, but volume overload may worsen the hypoxia.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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21. Vedrinne JM, Guillaume C, Gagnieu MC, Gratadour P, Fleuret C, Motin J. Bronchoalveolar lavage in trauma patients for diagnosis of fat embolism syndrome. Chest. Nov 1992;102(5):1323-7. [Medline].
22. White T, Petrisor BA, Bhandar M. Prevention of Fat Embolism Syndrome. Injury. 2006;37(Supplem 1):S59-67.
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Article Last Updated: Nov 9, 2007