Pathophysiology of Fat Embolism Syndrome
The pathophysiology of FES and specifically of CFE is not widely understood. Two main theories on the development of FES have been advanced.
The mechanical theory suggests that exposing intramedullary long-bone contents allows fat to mobilize into the bloodstream.19 This occurs in the setting of long-bone fracture and in canal preparation during joint replacement surgery. More fat extravasates into the venous system after femur fracture than after tibia fracture, which accounts for the higher risk for FES in femoral shaft fractures and the even higher risk in concomitant femur and tibia fractures.4 In addition to there being a risk of fat embolism from the fracture itself, placing the patient in traction or reaming the intramedullary canal may exacerbate this effect by increased extravasation of fat from the medullary canal. With extravasation of fatty bone marrow into the venous system, fat emboli are free to travel back to the lungs, where they can cause infarcts within the lung parenchyma.
In the mechanical theory, presence of PFO may allow fat globules to pass into the systemic circulation and cause end-organ emboli. In the event of cerebral emboli, neurologic symptoms may vary widely and may include diffuse encephalopathy and global deficits.20 Dog studies have found a possible mechanism for CFE in the absence of PFO. One such study, which used femoral pressurization to replicate cemented femoral arthroplasty, found that many fat globules had traversed the lungs after release into bone marrow,21 supporting the theory that fat droplets can traverse the pulmonary system without sequestration in the lung parenchyma. Riding and colleagues22 reported finding pulmonary arteriovenous shunts, which are thought to allow CFE to occur in the absence of PFO. More studies are needed to determine the prevalence of shunts and their overall contribution to CFE development in patients with long-bone fracture.
The biochemical theory holds that bodily trauma induces the release of free fatty acids (FFAs) from the capillaries into the bloodstream.23 This stress response is mediated by catecholamines, which activate the adenyl cyclase pathway, which activates lipase, which hydrolyzes stored triglycerides to FFAs and glycerol. The concentration of circulating FFA was increased in 9 of 10 patients in one study.23 Increased FFAs in the bloodstream can accelerate local and end-organ clotting, leading to thrombocytopenia and endothelial injury. In addition, patients with hypercoagulable diseases are at higher risk for postoperative thromboembolism.24 However, with a negative hypercoagulable work-up and with negative chest helical CT and EKG, which did not demonstrate PFO, the explanation for CFE in our patient may more likely reside with the arteriovenous shunt theory proposed by Riding and colleagues.22
Diagnosis and Treatment
Proper care of orthopedic patients who potentially have FES/CFE involves prompt diagnosis, immediate symptomatic care, and early coordination with neurology and medical services to rule out other causes of symptoms. Obtaining advanced imaging to rule out other potential causes and to confirm the diagnosis is crucial. The patient in this case report did not exhibit any focal neurologic deficits, but emergent CT of the brain was indicated to rule out a hemorrhagic event. If a stroke secondary to FES is clinically suspected, MRI should be obtained as soon as possible. Multiple studies have found that the “starfield” pattern, which is best seen as multiple punctate hyperintensities on T2 imaging, is the typical radiographic manifestation of CFE.9 This applies to patients who are in the 24- to 72-hour window after long-bone fracture or fixation and who fit Gurd and Wilson1 criteria or Lindeque1,2criteria, or who exhibit a change in mental status but have a negative CT scan of the brain, as was the case with our patient. Once the diagnosis is made, treatment involves addressing the symptoms (Figure 4).
Fat Embolism Syndrome in Reamed and Unreamed Nailing
Over the past several decades, the number of long bones fixed with intramedullary nails has increased significantly.26 There is debate regarding whether use of reamed intramedullary nails increases the risk of fat emboli relative to use of unreamed nails, but multiple studies have found no significant difference.26,27 Pulmonary shunting occurs in both reamed and unreamed nailing; neither technique has an advantage in terms of cardiopulmonary complications. In multiple studies, reamed nails have the advantage of improved healing rates.27 A sheep study compared reamed and unreamed femoral nailing.28 After nailing, sheep lungs were examined histologically for the presence of bone marrow fat embolism. The embolism rate was higher with unreamed nailing (10.25%) than with reamed nailing (6.66%). One large study of the adverse effects of reamed and unreamed nailing in 1226 patients with tibial shaft fracture found that those with open fractures had higher rates of a negative event (nonunion, infection, fasciotomy, hardware failure, need for dynamization) after reamed nailing.29 Patients with closed fractures had fewer events after reamed nailing. The authors concluded there is a potential benefit in outcome with reamed intramedullary nailing in patients with closed tibial shaft fractures, but they did not comment on development of FES. In a study of the effect of subject position on intramedullary pressure and fat embolism release, dogs were positioned either supine or lateral for tibial and femoral reaming.30 The authors measured various physiologic parameters, including cardiac output, pulmonary arterial wedge pressure, arterial and venous blood gas, and blood cell counts. There were no statistically significant differences in values between the 2 groups in any variable, indicating that position does not affect FES development in the orthopedic trauma setting.