Fat embolism syndrome

       Fat embolism syndrome

                        Dr. KS Dhillon

Fat embolism syndrome (FES) is an ill-defined clinical entity. It arises from the systemic manifestations of fat emboli within the microcirculation. Embolized fat within the capillaries causes direct tissue damage and induces a systemic inflammatory response resulting in neurological, pulmonary, cutaneous, and retinal symptoms. Fat embolism is most commonly seen following orthopedic trauma. Fat embolism can also be seen in patients with bone marrow transplants, pancreatitis, and following liposuction. The diagnosis of FES is difficult because no definitive diagnostic criteria or tests have been developed. Treatment for FES is largely supportive. Early operative fixation of long bone fractures decreases the likelihood of a patient developing FES.

Epidemiology

Fat embolization occurs frequently following orthopedic trauma. A study by Gurd and Wilson [1] found fat globules in the blood of 67% of orthopedic trauma patients. This number increased to 95% when the blood was sampled close to the fracture site [2].

Hypoxemia often suggests fat embolization causing subclinical FES. Almost all patients who are monitored with continuous pulse oximetry following a long-bone fracture have episodes of hypoxemia [3].

Embolization can occur during operative fixation of fractures. During nailing of long bone fractures, intraoperative transesophageal echocardiogram studies have detected fat embolization in 41% of patients [4].

Although fat globules can be detected in the blood of most patients and the patients can develop transient hypoxia, the actual incidence of FES is much lower. Bulger [5] reported a 19% incidence of FES in a group of trauma patients. Since early operative fixation of long-bone fractures has become standard treatment, most recent studies report an incidence of FES between 0.9% and 11% [6-8].

Pathophysiology

In patients with pulmonary embolism, fat particles enter the circulation and cause damage to capillary beds. The lungs are most frequently affected. Fat embolism can also affect the brain, skin, eyes, and heart.

There are two leading theories for the formation of fat embolism. They are the mechanical theory and biochemical theory. 

According to the mechanical theory, fat embolism occurs from the direct release of bone marrow into the venous system following trauma. Elevated intramedullary pressure following trauma leads to the release of fat through open venous sinusoids. The embolized fat obstructs the capillary beds. This can account for embolisms within the pulmonary capillaries. The theory, however, does not explain embolisms within the systemic capillaries beds. 

According to the biochemical theory, an inflammatory response to trauma causes the release of free fatty acids from the bone marrow into the venous system. The elevated free fatty acids and the inflammatory mediators cause damage to capillary beds. In patients with hypoxemia elevated free fatty acid levels have been found [9]. The free fatty acids induce inflammation within the lungs [10].

The end result is an intense inflammatory response. The capillary beds develop increased permeability and the inflammatory mediators damage surrounding tissues. In the lungs, this induces lung injury that is indistinguishable from acute respiratory distress syndrome (ARDS).

Clinical presentation

Embolized fat droplets can travel to microvessels throughout the body. Therefore, FES is a multiorgan disease that can damage any microcirculatory system in the body. Fat is known to embolize to the lungs, skin, brain, liver, retina, kidneys, and even the heart [11]. 

The symptoms usually present within 24 hours of inciting event. The patient complains of feeling short of breath and the patient appears confused. The presenting signs are usually nonspecific and can include tachypnea, tachycardia, and fever. The patient can have a petechial rash. Specific symptoms are dependent on the organ that is involved.

The pulmonary circulation is most commonly affected with up to 75% of patients experiencing respiratory depression [12,13]. The respiratory dysfunction can range from mild hypoxia requiring oxygen to ARDS requiring mechanical ventilation. Patients may decompensate rapidly to respiratory failure. While in the operating room the anesthetized patient can develop acute hypoxia secondary to FES.

FES can also produce nonspecific neurological symptoms. The symptoms arise due to cerebral edema rather than ischemia [14]. Patients can become lethargic or restless. When there is severe cerebral edema the patient may become unresponsive [15].

Dermal involvement produces a petechial rash. The rash may be present in about 50% of patients [16]. The rash tends to be transient. It lasts less than 24 hours. The torso is most commonly affected. The entire dermis and even mucosal membranes can be involved.

Hemorrhagic lesions of the retina can be seen in about 50% of patients [17]. These lesions are usually self-limiting and they disappear within weeks [18]. Residual visual deficit is uncommon.

Patients can also develop thrombocytopenia or a decrease in hemoglobin levels.

Diagnosis

Diagnosis of FES can be challenging since FES is a heterogeneous disease with no pathognomonic features.  Gurd [19] proposed a clinical criteria for diagnosing FES in 1970. He later modified it with Wilson[1] [Table 1]. Schonfeld [20] suggested a scoring system to help in the diagnosis of FES [Table 2]. Lindeque [21] proposed that FES can be diagnosed based on respiratory changes alone [Table 3]. None of these criteria have been validated or have been accepted universally.

 

 

Table 1

Gurd and Wilson's criteria for FES

 

 

 

 

Table 2

Schonfeld's scoring system for FES

Table 3

Lindeque's criteria for FES

Respiratory distress is the most clinically significant feature of FES in the acute setting. Respiratory distress from FES is usually indistinguishable from ARDS which is seen in polytrauma patients. White [22] has defined FES as ARDS with additional organ involvement due to long bone trauma.

Laboratory and imaging tests can help in the diagnosis of FES, but the tests are nonspecific. Patients will demonstrate hypoxemia on arterial blood gas while on room air. A chest x-ray will often show diffuse interstitial infiltrates. A chest CT scan will show diffuse areas of vascular congestion and pulmonary edema.

Microscopic examination of urine, blood, or sputum may show fat globules, but this finding is nonspecific.

Bronchoalveolar lavage (BAL) has been investigated as a diagnostic tool for FES [23-25]. Lipid inclusions within macrophages can be quantified.  BAL is invasive and time consuming. It is not widely used in diagnosing FES.

Treatment

Pharmacologic interventions

Pharmacologic therapeutic interventions developed specifically for FES have been largely unsuccessful. The use of dextrose to decrease free fatty acid mobilization or ethanol to decrease lipolysis has not shown clinical benefit [26,27]. Anticoagulation with heparin has been found to be beneficial in animal models but it is no longer used in clinical practice due to the risk of bleeding and unproven benefit [28-30].

Corticosteroid therapy has been proposed as a potential therapy for FES. It limits free fatty acid levels, stabilizes membranes, and inhibits complement mediated leukocyte aggregation. A meta-analysis of seven randomized trials by Bederman et al [31] showed that the use of prophylactic corticosteroids in patients with long-bone fractures reduced the risk of FES by 77%. The meta-analysis also showed no difference in mortality, infection, and avascular necrosis in patients treated with corticosteroids as compared to the control patients. 

Some clinicians administer corticosteroids to patients with long-bone fractures as FES prophylaxis. The most commonly used steroid is methylprednisolone in dosages ranging from 6 to 90 mg/kg.

There have been suggestions to place inferior vena cava filters to reduce the showering of emboli to the pulmonary vasculature. The use of IVC filters as a prophylactic treatment to prevent FES has not been sufficiently studied.

Supportive treatment

The definitive treatment for a patient who has developed FES is supportive care of the involved organ. Supplemental oxygen is usually needed to improve oxygenation. If ARDS develops the patient may require mechanical ventilation. Intravenous fluid may be required for resuscitation if the blood pressure is low. In severe cases where there is right ventricular failure due to pulmonary embolism, ionotropic support with dobutamine may be necessary [32].

Patients who have neurological manifestations require frequent neurological examinations and documentation of the Glasgow Coma Scale. Rapid deterioration can develop from increased cerebral edema [15]. Patients with FES and cerebral edema may need an intracranial pressure monitor in order to monitor the treatment of cerebral edema [33].

Operative fixation of fractures

Early operative fixation of long-bone fractures reduces the incidence of FES. When long bone fractures are treated conservatively with prolonged immobilization, the incidence of FES is about 22% [34]. The movement of fracture ends has been shown to result in transient showering of fat emboli [35]. Cytokines remain elevated in patients undergoing conservative treatment and they return to normal after operative treatment of the fracture [36].

The incidence of FES is reduced by early internal fixation of long bone fractures [37]. There are several retrospective studies that have reported reduced incidence of FES with the use of internal fixation devices [7,38-43]. A study by Johnson et al [39] showed that patients undergoing fixation urgently had an incidence of ARDS of 7% compared to an incidence of ARDS of 39% in patients who had fixation delayed by more than 24 hours.

An increase in intramedullary pressure during fracture fixation increases the amount of fat emboli entering the circulation [44].

Although reaming can increase intramedullary pressure, reaming has not been shown to increase the incidence of FES. A randomized trial by Anwar et al [45] comparing pulmonary complications in patients undergoing bone fixation with reamed nailing and unreamed nailing found no difference between the two groups. In patients undergoing bone fixation with reamed and unreamed nails there is visible pulmonary embolism seen on transesophageal echocardiography [46].

Various surgical techniques to reduce embolization such as drilling holes in the cortex to reduce intramedullary pressure, lavaging bone marrow prior to fixation to reduce marrow for embolization, venting of the femur, use of a bone-vacuum, and use of tourniquets have been tried but none of them have reduced FES [47-51].

Morbidity and mortality

The outcome of FES is favourable with supportive care and early fixation of fractures. The development of ARDS is the most significant morbidity in patients with FES. Most patients, however, can expect a complete recovery from the pulmonary, neurologic, and retinal involvement. Mortality rates of between 7% and 10% have been reported from FES in modern studies utilizing supportive measures and early operative fixation [5,6].

Conclusion

Orthopedic trauma patients with FES usually present with respiratory distress. There are no specific diagnostic tests or criteria for diagnosis of FES, hence the syndrome is most often a diagnosis of exclusion. Treatment is usually directed at the treatment of ARDS and support of other organ systems affected by fat embolization. Early operative fixation of long-bone fractures reduces the incidence of FES.

References

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