Fat embolism syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

In 1861, Zenker first discovered fat embolism (FES), after he found pulmonary capillary fat deposition in a patient who suffered from crush injury. In 1873, Bergmann described the first clinical case of FES in a patient who suffered a distal femur fracture. In 1875, Czerny explored cerebral symptoms associated with FES.

The historical perspective of fat embolism syndrome is as follows:^[1][2][3]

• In 1861, Zenker first discovered fat embolism (FES), after he found pulmonary capillary fat deposition in a patient who suffered from crush injury.
• In 1873, Bergmann described the first clinical case of FES in a patient who suffered a distal femur fracture.
• In 1875, Czerny explored cerebral symptoms associated with FES.^[4][5]
• In 1924, Gauss proposed the mechanical theory, which explains that three conditions are necessary for the development of fat embolism: injury to adipose tissue, rupture of veins within the zone of injury, and a mechanism that causes the passage of free fat into the open ends of blood vessel.^[6][7]
• In 1927, Lehman established biochemical theory which states that plasma mediators mobilize fat from body stores and cause the agglutination of bigger fat droplets and hence initiate an inflammatory process.

• In1939, Kuntscher was the first to describe the association between increased intramedullary pressure due to intramedullary nailing and fat emboli.^[8][9]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

There is no established system for the classification of fat embolism syndrome.

There is no established system for the classification of fat embolism syndrome.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Fat embolism syndrome (FES) is the presence of fat globules in the circulation post traumatic insult which can lodge into the small sized capillaries in the lung, brain and skin leading to devastating clinical manifestations. The two widely accepted theories which explain the pathophysiology of FES are mechanical and biochemical theory. The mechanical theory proposes that there is mechanical obstruction by fat cells from the bone marrow in the end-capillaries after trauma. Biochemical theory attributes the clinical manifestations of FES to the pro inflammatory effect of fat emboli.

Two major theories have been described to explain the pathophysiology of fat embolism syndrome(FES):^[1][2]

• Mechanical theory
• Biochemical theory

The theory proposes that there is mechanical obstruction by fat cells from the bone marrow in the end-capillaries after trauma.

• Post traumatic insult, the fat cells travel via venous sinusoids to the capillaries.
• These cells have potent prothrombotic and proinflammatory potential.
• They trigger rapid aggregation of platelets and accelerated fibrin generation as they travel through the venous system, eventually lodging in the pulmonary arterial circulation.
• Pulmonary capillary obstruction leads to interstitial hemorrhage and edema, alveolar collapse, and reactive hypoxemic vasoconstriction.
• Massive fat emboli may also lead to macrovascular obstruction and shock.
• Fat cells may also enter the arterial circulation via a patent foramen ovale or directly through the pulmonary capillary bed, causing the characteristic neurological and dermatologic findings of FES.

This theory attributes the clinical manifestations of FES to the pro inflammatory effect of fat emboli.^[3][4][5]

• Tissue lipases break down the fat in the bone marrow, forming high levels of the following toxic intermediaries:^[6][7]
  • Free fatty acids:

Free fatty acids are released into the circulation after hydrolysis and deposit into the end capillaries of the lung, manifesting as acute respiratory distress syndrome.^[8][9]

• Cytokines:

Patients with FES are also found to have high levels of certain cytokines such as tumor necrosis factor alpha, phospholipase A2, interleukin 1 and 6.^[10][11]

• C-reactive proteins:

The elevation in c-reactive proteins is responsible for lipid agglutintion in FES which results in microvasculature obstruction and stagnant blood flow.

• Eventually, these intermediate products lead to end-organ dysfunction.
• In the lung, toxic injury to pneumocytes and pulmonary endothelial cells causes vasogenic and cytotoxic edema as well as hemorrhage.
• Acute lung injury or acute respiratory distress syndrome results from damaged pulmonary endothelium that triggers a proinflammatory cytokine cascade.

Following pathological sequence of events occur after an orthopedic trauma such as long bone fracture.

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• There is no genetic association of FES.

There is no characteristic gross pathology associated with fat embolism.

Hematoxylin and eosin staining shows the following changes in the lungs, kidneys and brain:^[12]

Lung:

• Alveolar haemorrhagic edema
• Fat droplet deposition
• Fibrin thrombi
• Multiple fat droplets

Immunohistochemical staining shows the following changes:

• Raised levels of iNOS in the alveolar macrophages.

Kidney:

• Hematoxylin and eosin staining shows fat deposits in the glomeruli.

Brain:

• Fat droplets are seen in vessels.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

The causes of fat embolism syndrome can be divided into trauma and non-trauma related. The most common cause of fat embolism syndrome is long bone fracture especially the femur. Other causes include orthopedic procedures, liposuction, pelvic fractures and soft tissue injury.

The causes of fat embolism syndrome can be divided into trauma and non-trauma related.

The common causes of fat embolism are divided into trauma-related and non-trauma related.^{[1][2][3][4][5]}

Rare causes of fat embolism syndrome are as follows:^[12][13][14]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Fat embolism syndrome should be differentiated from other diseases presenting with chest pain, shortness of breath, tachypnea and neurological deficits. FES must be differentiated from meningitis, pneumonia, pulmonary embolism, stroke, thrombotic thrombocytopenic purpura.

Fat embolism syndrome should be differentiated from other diseases presenting with chest pain, shortness of breath and tachypnea. The differentials include the following:^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

The exact incidence of FES is unknown and is estimated to be of <1% to >30% of all trauma cases. It commonly affects individuals 10-40 years of age. Fat embolism syndrome more commonly affects men more than women.

• The exact incidence of FES is unknown.
• The estimated annual incidence of FES in the orthopedic and trauma literature, has ranged from <1% to >30% of cases.
• This varying incidence is attributed due to difference in the diagnostic criteria employed.

• The incidence of fat embolism syndrome increases with age.
• It commonly affects individuals 10-40 years of age.^[1]

• There is no racial predilection to fat embolism syndrome.

• Fat embolism syndrome more commonly affects men more than women.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

The risk factors playing an important role in the development of fat embolism are blunt trauma, acute pancreatitis, diabetes mellitus, long bone fractures and liposuction.

The following risk factors play an important role in the development of fat embolism.^[1][2][3]

• Blunt trauma
• Male sex
• Acute pancreatitis
• Diabetes mellitus
• Burns
• Long bone fracture^[4][5]
• Joint reconstruction
• Liposuction
• Alcoholic liver disease
• Sickle cell crisis
• Cardiopulmonary bypass
• Decompression sickness

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Fat embolism syndrome commonly occurs 12-24 hrs after the inciting event. It can occur as early as 12 hrs and as late as 2 weeks. Patients are often dyspneic, tachypneic and hypoxic. Complications of fat embolism syndrome include disseminated intravascular coagulation, right ventricular dysfunction, acute respiratory distress syndrome and shock. Most patients recover with supportive treatment. Mortality occurs in 5-15% of patients.

Fat embolism syndrome commonly occurs 12-24 hrs after the inciting event. It can occur as early as 12 hrs and as late as 2 weeks. Patients are often dyspneic, tachypneic and hypoxic. if left untreated, patients can progress to develop the following features:

• 50% of patients with FES require mechanical ventilation
• Progression to adult respiratory distress syndrome (ARDS)
• Majority of patients develop neurologic abnormalities.
• Acute confusional state
• Coma
• Disseminated intravascular coagulation (DIC)
• Cardiogenic shock

The complications of fat embolism syndrome are as follows:

• Disseminated intravascular coagulation
• Right ventricular dysfunction
• Acute respiratory distress syndrome
• Shock
• Biventricular failure
• Death

The prognosis of fat embolism syndrome is as follows:^[1]

• Most patients recover spontaneously.
• With supportive care alone, the outcome of the disease is relatively better.
• Mortality occurs in 5-15% of patients.