Critical Care Medicine
Also known as: Fat Embolism Syndrome (FES)
1. Description of the problem
What every clinician should know
Fat embolism is the presence of fat in the circulatory system and may be associated with a variety of conditions.
Most commonly associated with long bone and pelvic fractures, fat embolism is thought to be secondary to disruption of the bloodstream with fat entry. Another possibility for the pathogenesis of fat embolus is production of toxins from the degradation and agglutination of fat including free fatty acids and C-reactive protein. Samples taken from the pulmonary vasculature at autopsy after skeletal trauma demonstrate that fat is present in 90% of patients, and fat can be found in the pulmonary arterial blood samples of almost 70% of patients with long bone and pelvic trauma. FES is seen more often in patients with closed fractures as well as an increasing number of fractures. There are variable reports in the literature regarding the development of FES. In 1996, Johnson et al. reported an incidence of up to 33% in patients with bilateral femur fractures.
FES does not develop in all patients with fat embolism but develops when fat globules deposit in the lungs. The classic signs include hypoxemia, decreased mental status and petechial rash, which can progress to acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). FES usually presents within 24-72 hours after the injury but has been seen from 12 hours up to 2 weeks after the insult.
The earliest clinical finding is hypoxemia, dyspnea and tachypnea. A large number of patients develop neurologic symptoms that present as confusion progressing to an altered level of consciousness. The pathognomonic petechial rash above the nipple line is seen in only 20-50% of cases. Other symptoms include fever, cardiac dysfunction, retinopathy and thrombocytopenia. The diagnosis of FES is often one of exclusion as the clinical signs and symptoms are non-specific and can be seen in a variety of disease processes. The clinical presentation plays an important role in aiding the diagnosis, as there is no test for fat embolism or FES.
Key management points
Management of FES is supportive and centers around the management of any patient with ARDS. Ventilator strategies include use of tidal volumes of 6-8ml/kg, high PEEP and maintaining plateau pressures less than 30 mmHg. Seizures and focal neurological deficits have been described but are uncommon. The neurologic sequelae of FES are short and usually reversible. The petechial rash if present typically resolves in a week.
2. Emergency Management
The emergency management of fat embolism or of FES is to follow the ABCs. If the patient's condition deteriorates, supportive care is indicated with hemodynamic monitoring, fluid administration and vasopressors as indicated.
Consideration should be given to managing the patient with noninvasive cardiac output monitoring or echocardiography to assess filling and function.
Management points not to be missed
Management of fat embolism and FES begins with prevention. Early immobilization of fractures and operative correction are key to decreasing the development of these conditions. Robinson demonstrated a 70% decrease in pulmonary complications with early fixation. Some advocate traction until the patient is hemodynamically stable for definitive fixation. Patients with lung contusions have a higher incidence of edema and may have an exaggerated pulmonary response to fat embolism.
Different intraoperative techniques have been shown to reduce the possibility of developing FES. Pitto et al demonstrated that decreasing the intraosseous pressure, which reduces the intravascular accumulation of fat and debris, may reduce the development of FES. These authors randomly assigned patients to receive a venting hole during cemented total hip arthroplasty and found that the group with venting holes had a 20% rate of major embolic events vs. 85%.
A prospective, randomized control trial looking at 20 patients at a Level 1 Trauma Center compared the use of a conventional reamer versus a reamer-irrigator-aspirator (RIA) for IM nailing and found that RIA produced less fat visible in the right atrium using trans-esophageal echocardiography. IM nailing has also been shown to increase pulmonary permeability, activation of leukocytes and development of edema.
Pharmacologic therapies have been tried to reduce the inflammatory response to fat embolus without resounding success or endorsement. In rats, fat embolism was produced with installation of corn oil micelles and ALI was determined by lung weight changes and cytokine levels. Animals were given N-acetylcysteine, which alleviated the pathologic and biochemical changes seen in the lab model of fat embolism. Inhibitors of nitric oxide synthase such as N-omega nitro-L-arginine methyl ester were also able to ameliorate the fat embolism changes seen in rats.
Captopril and Losartan have both been shown to reduce the vasoconstriction, inflammation and fibrosis associated with fat embolism 48 hours after injury in rats. Clinical trials have demonstrated benefit with prophylactic administration of corticosteroids, but this practice has not been widely adopted. A meta-analysis demonstrated a decreased risk of FES by 78%, with NNT of 8 to prevent 1 case.There were no differences in mortality or infection. The evidence is Grade 2C for those at high risk with long bone or pelvic fractures.
Fat embolism or FES is primarily a clinical diagnosis. A heightened awareness of conditions associated with FES and a high index of suspicion are necessary to facilitate this diagnosis.
Possible Clinical Findings in FES
|Altered mental status|
|Hypotension, Shock, CV Collapse|
|Oliguria and anuria|
Conditions associated with FES
|Surgical including Injury|
|Long bone fractures|
|Other fracture of marrow bone|
|Bone marrow harvest/transplant|
|Gluteal fat injection/liposuction|
|Sickle cell hemoglobinopathies|
|Bone tumor lysis|
|Infusion of lipids|
|Solvent of cyclosporine A|
|Carbon tetrachloride poisoning|
There are no laboratory tests to confirm the diagnosis of fat embolism or FES. Fat globules may be seen on funduscopic exam of the retina and on microscopic exam of the urine, but they are not necessary to make the diagnosis.
Radiographic diagnosis of fat embolism is confirmatory, not diagnostic. Different methods of imaging have been used in patients with presumed FES. CXR's are generally normal. CT of the chest may show bilateral ground-glass opacities and intralobar septal thickening in fat embolism. MRI of the brain can show a diffuse, hyper-intense punctuate signal of T2-weighted images.
Transcranial Doppler has been shown to demonstrate the presence of microemboli in the cerebral circulation. A recent prospective trial evaluated 14 patients with femur fracture by using transcranial Doppler, daily neurologic exam and evaluation for the presence of a right-to-left shunt. The authors found that patients with a right-to-left shunt had larger microembolic signals detected by Doppler. These signals correlated with daily exam findings and can predict the development of neurologic symptoms in patients with femur fracture.
Due to the presence of fat in the lungs, studies have been attempted with bronchoalveolar lavage (BAL) to attempt to differentiate FES from ALI or ARDS. As yet, there is no conclusive test by BAL to diagnose FES.
4. Specific Treatment
Treatment of FES is supportive and, as already stated, a diagnosis of exclusion. When associated with ALI and ARDS, it is imperative that the practitioner have vigilance to monitor for other treatable causes of respiratory compromise.
Refer to Sections 2 and 3, Emergency Management and Diagnosis, for a more in-depth discussion of treatments specific to FES that have been shown to ameliorate the effects in animals and may have promise in humans.
There are two proposed hypotheses for the pathogenesis of fat embolism and FES. This condition is thought to be either mechanical, from entrance of fat globules into the bloodstream, or chemical, from degradation of fat globules releasing toxic intermediates, or a combination of both.
The mechanical theory is that disruptions in bone marrow and adipose tissue or increases in intramedullary pressure allow fat to enter the venous system through the sinusoids. This theory is supported by evidence of fat seen in the heart during orthopedic surgery. Entrance into the arterial circulation occurs with and without the presence of a patent foramen ovale through microemboli.
The chemical theory is that when lipoprotein lipase acts on the fat globules, C-reactive protein and free fatty acids are released. These cause not only a local and systemic inflammatory response but can also lead to direct injury by agglutination and vascular obstruction. Free fatty acids and other mediators are associated with inflammatory reactions in the lungs like pneumonitis and vasculitis. This pathway for inflammatory response is thought to mimic that of ALI and ARDS. A study in rats with corn oil-induced FES revealed not only markers of inflammation but also microvascular obstruction, increases in permeability and pulmonary hypertension. The toxic biochemical mediators that they identified include the inflammatory cytokines as well as phospholipase A2, nitric oxide and inducible nitric oxide synthase.
The delay in development of FES from time of injury lends credence to the theory that this is a multifactorial disease process.
The epidemiology of fat embolus and FES is uncertain, largely due to the lack of diagnostic criteria. In retrospective reviews, the incidence of the clinical syndrome is < 1%. A 10-year review of patients with long bone fractures and symptoms consistent with FES showed an incidence of 0.9%. Data from the National Hospital Discharge Survey from 1979-2005 identified 41,000 patients with FES. Of these patients, those with a single-site fracture had an incidence of 0.12%.
Patients with multiple femur fractures had a 1.29% incidence, while those with single femur fractures had an incidence of 0.54%. Isolated neck fractures of the femur had an incidence of 0.06%. Rarely, if ever, were non-orthopedic patients or children < 9 years old diagnosed with FES. Patients aged 10-39 were most commonly affected. Men had a relative risk of 5.71 of developing FES. Possibilities for low risk among children include decrease in overall fat content. Elderly patient population fractures tend to involve the femur neck and have the lowest incidence of FES from femoral fractures.
Factors that influence the development of FES in patients include but are not limited to age, gender, number and location of fractures (
FES Risk Factors
|Fractures with Greatest Risk|
|IM femur nailing|
|Lower extremity joint replacement|
The estimated mortality rate of patients with FES is 5-15%. The majority of the morbidity and mortality associated with this condition is due to the development of ARDS. Meta-analysis of 166 patients with long bone fractures and FES reported only two deaths, for a mortality rate of 1.2%. The etiology of ARDS in a patient may be difficult to determine, and this is the most likely reason for the discrepant incidence and mortality rates reported in the literature. Worst outcomes are seen in patients with severe neurologic injury. Survivors have an excellent prognosis with minimal long-term sequelae of FES.
What's the evidence?
Hulman, G. "The pathogenesis of fat embolism". J Pathol. vol. 176. 1995. pp. 3-9.(This article describes the two basic mechanisms that cause fat to embolize: direct deposit of fat due to trauma and agglutination of endogenous or infused exogenous fat with embolism.)
Akhtar, S. "Fat embolism". Anesthesiol Clin. vol. 27. 2009. pp. 533-50.(Extremely well-written, thorough review of fat embolism defining the disease, epidemiology, etiology, pathophysiology, clinical presentation, diagnosis, management and prognosis of FES. If you have time for only one reference, this is it.)
Johnson, MJ, Lucas, GL. "Fat embolism syndrome". Orthopedics. vol. 19. 1996. pp. 41-8.(Review article of classic literature on FES including cause, pathophysiology, presentation, diagnosis and treatment. This article specifies that clinical suspicion and diagnosis is the key. Treatment modalities are summarized well for the learner.)
Carr, JB, Hansen, ST. "Fulminant fat embolism". Orthopedics. vol. 13. 1990. pp. 258-61.(Often-cited article that summarizes content, theory and practical treatment measures for patients with fat embolism.)
Kaplan, RP, Grant, JN, Kaufman, AJ. "Dermatologic features of the fat embolism syndrome". Cutis. vol. 38. 1986. pp. 52-5.(Dermatologic review of manifestations, features of fat embolism syndrome.)
Robinson, CM. "Current concepts of respiratory insufficiency syndromes after fracture". J Bone Joint Surg Br. vol. 83. 2001. pp. 781-91.(This article describes that early fixation of major orthopedic injuries has significantly reduced pulmonary complications from these injuries. The best treatment option is prevention.)
Pitto, RP, Schramm, M, Hohmann, D, Kössler, M. "Relevance of the drainage along the linea aspera for the reduction of fat embolism during cemented total hip arthroplasty. A prospective, randomized clinical trial". Arch Orthop Trauma Surg. vol. 119. 1999. pp. 146-50.(This article prospectively randomized 40 patients to drainage via a venting hole or not in patients undergoing total hip arthroplasty. TEE was used to observe as well as hemodynamic and blood gases. Severe embolic events were found in 85% of patients without vent and in 20% of patients with vent for drainage.)
Volgas, DA, Burch, T, Stannard, JP, Ellis, T, Bilotta, J, Alonso, JE. "Fat embolus in femur fractures: a comparison of two reaming systems". Injury. vol. 41. 2010. pp. S90-3.(Prospective, randomized trial in Level 1 trauma center using two reamer systems for placement of IM nail for femur fracture by monitoring right heart fat via TEE. The reamer-irrigator-aspirator showed a nearly significant decrease in volume of fat as a conventional reamer.)
Liu, DD, Kao, SJ, Chen, HI. "N-acetylcysteine attenuates acute lung injury induced by fat embolism". Crit Care Med. vol. 36. 2008. pp. 565-71.(This study used lungs from 36 rats and randomized them to receive saline solution, FE or FE with N-acetylcysteine treatment. The corn oil micelle model induces acute lung injury with associated biochemical changes. Treatment with N-acetylcysteine alleviates the pathologic and biochemical changes from FE.)
Chen, HI. "From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome". Chin J Physiol 2009 Nov. vol. 52. 30. pp. 339-44.(These authors used a corn oil model to induce FES in fourteen rats to examine the biochemical markers produced. They found release of cytokines, nitric oxide and others and demonstrated that antioxidants and NOS inhibitors abrogated fat embolism changes.)
McIff, TE, Poisner, AM, Herndon, B, Lankachandra, K, Molteni, A, Adler, F. "Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism". J Trauma. vol. 70. 2011. pp. 1186-91.(Rats were given triolein intravenously to mimic FES. One hour later they were given captopril (Ang I converting enzyme inhibitor) or losartan (Ang II type 1 receptor blocker). Histology 48 hours later revealed decreased inflammatory, vasoconstrictor and profibrotic effects in lungs of rats treated with either captopril or losartan.)
Bederman, SS, Bhandari, M, McKee, MD, Schemitsch, EH. "Do corticosteroids reduce the risk of fat embolism syndrome in patients with long-bone fractures? A meta-analysis". Can J Surg. vol. 52. 2009. pp. 386-93.(This article reviewed randomly assigned groups to corticosteroids or standard treatment of FES from 1966 to 2006. Primary outcome was development of FES. Of the 104 studies identified, 7 met criteria. Steroids reduced development of FES and risk of hypoxia with no difference in mortality of infection.)
Malagari, K, Economopoulos, N, Stoupis, C, Daniil, Z, Papiris, S, Müller, NL, Kelekis, D. "High-resolution CT findings in mild pulmonary fat embolism". Chest. vol. 123. 2003 Apr. pp. 1196-201.(This article, retrospective and prospective, reviews nine patients with FES using high-resolution CT of chest. Patterns of CT were recorded and analyzed. CT findings document ground-glass opacities in seven patients with thickened interlobular septa in five patients, patchy distribution in four patients and nodular pattern in two patients. Abnormalities resolved on average within 16.4 days.)
Shobha, N, Bermejo, PG, Bhatia, R, Choi, Y, Smith, EE, Demchuk, AM. "Multimodal imaging tools for diagnosis of fat embolism". J Emerg Trauma Shock. vol. 4. 2011. pp. 306-8.(This case study discusses a patient with probable FES whose diagnosis was confirmed by transcranial Doppler embolic signals and magnetic resonance imaging changes.)
Forteza, AM, Koch, S, Campo-Bustillo, I, Gutierrez, J, Haussen, DC. "Transcranial Doppler detection of cerebral fat emboli and relation to paradoxical embolism: a pilot study". Circulation. vol. 123. 2011. pp. 1947-52.(This prospective study looked at forty-two patients with femoral shaft fracture and evaluated for right-to-left shunt. They used a transcranial Doppler to see if there was evidence of emboli and if it was more pronounced with patients who had a shunt. Presence of shunt had more embolic brain signals and predicted neurologic symptoms.)
Karagiorga, G, Nakos, G, Galiatsou, E, Lekka, ME. "Biochemical parameters of bronchoalveolar lavage fluid in fat embolism". Intensive Care Med. vol. 32. 2006. pp. 116-23.(This article prospectively studied thirteen patients with FES and compared them to eleven patients with other causes of ALI/ARDS by comparing BAL fluid. They found higher levels of total cholesterol, lipid esters, monoglycerides, and phospholipase A2 in FES group.)
Koessler, MJ, Fabiani, R, Hamer, H, Pitto, RP. "The clinical relevance of embolic events detected by transesophageal echocardiography during cemented total hip arthroplasty: a randomized clinical trial". Anesth Analg. vol. 92. 2001. pp. 49-55.(This prospective study looked at relationship between embolic events during cemented total hip arthroplasty techniques and TEE. The modified technique with decreased intramedullary pressure had 13% embolic events vs. 93%. There were no clinical signs of fat embolism.)
Eriksson, EA, Schultz, SE, Cohle, SD, Post, KW. "Cerebral fat embolism without intracardiac shunt: A novel presentation". J Emerg Trauma Shock. 2011. pp. 309-12.(This case report describes a posttraumatic death from diffuse fat embolization to brain and lungs without a right-to-left shunt.)
Mellor, A, Soni, N. "Fat embolism". Anaesthesia. vol. 56. 2001 Feb. pp. 145-54.(Review article that looks at incidence, etiology, pathophysiology, diagnosis and treatment of fat embolism. Supportive treatment results in good outcomes.)
Bulger, EM, Smith, DG, Maier, RV, Jurkovich, GJ. "Fat embolism syndrome. A 10-year review". Arch Surg. vol. 132. 1997. pp. 435-9.(This article was a ten-year review of patients diagnosed with FES at a Level 1 trauma center from 1985 to 1995. Twenty-seven patients were identified with incidence of 0.9% with long bone fractures. The authors divided patients and found 96% had hypoxia, 59% had mental status changes and 33% had petechial rash. This remains a diagnosis of exclusion.)
Stein, PD, Yaekoub, AY, Matta, F, Kleerekoper, M. "Fat embolism syndrome". Am J Med Sci. vol. 336. 2008. pp. 472-7.(These authors reviewed patients discharged from 1979 to 2005 from the National Hospital Discharge Summary using ICD-9 codes. They demonstrated that the incidence of FES depends on bone involved, number of fractures, age and gender of patient. They conclude that FES rarely is the result of a medical condition.)
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