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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 56-63

Fat embolism syndrome: A comprehensive review and update


Department of Orthopaedic Surgery, King George Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication19-Dec-2018

Correspondence Address:
Dr. Shailendra Singh
Room No. 421, Department of Orthopaedic Surgery, King George Medical University, Lucknow - 226 003, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joas.joas_18_18

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  Abstract 


Fat embolism syndrome (FES) is a life-threatening situation, which warrants greater emphasis than it receives in the literature. FE occurs following various medical and surgical conditions leading to a cascade of systemic inflammatory process affecting multiple organs of the body, which may lead to end-organ failure. It has high mortality and morbidity. Despite advancement in science and technology, diagnosis of this fatal syndrome is mainly based on clinical symptoms and signs and no major definitive diagnostic tool and treatment method is available. At present, treatment of this disastrous medical condition is only supportive. In this review, we summarize the incidence, etiology, pathophysiology, and management of FES.

Keywords: Fat embolism syndrome, organ failure, polytrauma


How to cite this article:
Singh S, Goyal R, Baghel PK, Sharma V. Fat embolism syndrome: A comprehensive review and update. J Orthop Allied Sci 2018;6:56-63

How to cite this URL:
Singh S, Goyal R, Baghel PK, Sharma V. Fat embolism syndrome: A comprehensive review and update. J Orthop Allied Sci [serial online] 2018 [cited 2019 Jan 17];6:56-63. Available from: http://www.joas.in/text.asp?2018/6/2/56/247959




  Introduction Top


Although a rare clinical condition, fat embolism syndrome (FES) is an alarming multidisciplinary phenomenon difficult to diagnose but if missed, may lead to death. Historically known from very past, it was first described by Zenker in 1861 that it is associated with long-bone fractures and often presents as a combination of neurological, pulmonary, dermatological, and hematological symptoms and observed fat deposition in the pulmonary capillaries during autopsy.[1] Later in 1873, the first clinical case of FES was described by Bergmann in a patient of distal femur fracture.[2] The actual incidence of FES is unknown as it varies significantly according to the cause and mild cases remain unnoticed very often but incidence of FES ranges from 0.5% to 29% in different studies. As reported by Bulger et al.,[3] in their retrospective study, incidence of FES was <1% whereas by Fabian et al. in their prospective study, it was 11%–29%.[4] Overall mortality from FES had been reported from 5% to 15%.[5] It would be wise to know that two clinical conditions “Fat Embolism” and “Fat Embolism Syndrome” although closely related but have completely different meaning. The term FE is described as the asymptomatic mechanical blockage of vascular channels by circulating fat globules in the lung parenchyma and peripheral circulation and term FES is described as the serious consequences of fat emboli producing a distinct pattern of clinical manifestations.[6] Hence, the FES is a rare clinical entity in which circulating fat emboli or fat macroglobules lead to multisystem dysfunction which typically presents 24–72 h after the initial injury.


  Etiology Top


FES may be associated with a variety of clinical conditions both traumatic as well as nontraumatic. Various clinical conditions complicated by FES are enumerated as follows.[7]

Conditions associated with FE:

  1. Trauma related


    1. Long-bone fractures
    2. Pelvic fractures
    3. Fractures of other marrow-containing bones
    4. Orthopedic procedures
    5. Soft-tissue injuries (e.g., chest compression with or without rib fractures)
    6. Burns
    7. Liposuction
    8. Bone marrow harvesting and transplant


  2. Nontrauma related


    1. Pancreatitis
    2. Diabetes mellitus
    3. Osteomyelitis and panniculitis
    4. Bone tumor lyses
    5. Steroid therapy
    6. Sickle cell hemoglobinopathies
    7. Alcoholic (fatty) liver disease
    8. Lipid fusion
    9. Cyclosporine A solvent.


Various risk factors have been identified in the recent studies for increases the risk for development of FES in a patient [Table 1].[8],[9],[10],[11],[12]
Table 1: Risk factors for fat embolism syndrome

Click here to view


It is reported in a study that patients with a single long-bone fracture have a 1%–3% chance of developing the FES, but it increases up to 33% in patients with bilateral femoral fractures.[9]


  Pathophysiology Top


Although FES genesis is an extremely complex phenomenon, various theories had been given in the past regarding this.

Gauss' mechanical theory

In 1924, Gauss established the mechanical theory which points out the necessity of three factors for the development of FES.[13]

  1. Injury to adipose tissue
  2. Rupture of veins within the injury area
  3. Passage of free fat into the open ends of the blood vessels.


According to this theory, the highest incidence of FES in long-bone fractures may be because of the disruption of venules in the marrow, which remain tethered open by their osseous attachments. Detection of FE in the form of passage of “echogenic material” by transesophageal echocardiography (TEE) during an orthopedic procedure supports this.[12]

As FE is initially a venous phenomenon, so it is naturally expected that the lungs will be the first as well as most commonly affected organs. These fat emboli must migrate from venous circulation to arterial circulation to involve other body organs which can happen in various ways.

  1. Paradoxical embolism: With continued venous embolism, the right atrial pressure rises which promote the passage of fat material through a patent foramen ovale into the arterial circulation.[14] In about 20%–34% of normal adult population, this foramen ovale remains patent. It was also reported that even in individuals in whom this foramen was closed, it might be opened by the occurrence of acute pulmonary hypertension such as those that may occur in a massive FE[14],[15],[16],[17],[18],[19]
  2. Sometimes, the emboli are so small that they can easily pass from the venous to the arterial circulation through the lungs[20]
  3. Fat droplets themselves have a great deformation potential and by taking a more elongated form, these can pass through pulmonary capillaries[21]
  4. In a study, it was proposed that during the period of exercise and hypoxia, there occurs an increase in arteriovenous anastomosis creating a conduit for fat emboli to be systemically released[22]
  5. Gossling et al. reported that there are certain anatomical pulmonary arteriovenous microfistulas in the body through which fat globules even with a diameter 20–40 times larger than pulmonary capillary can reach the systemic flow.[23]


This mechanical theory of FES development has certain limitations:

  1. It does not explain the development of nontraumatic FES
  2. It does not explain the 24–72 h interval delay for FES development following the acute insult.



  Lehman's Biochemical Theory Top


In 1927, Lehman proposed a theory which states that production of toxic intermediates from plasma-derived fat molecules is responsible for development of FES.[24] There are a number of biochemical mechanisms which are involved in FES. The embolized neutral fat globules as found in bone marrow do not cause acute lung injury (ALI). These are degraded into various toxic intermediates such as free fatty acids (FFAs), C-reactive proteins, and catecholamines which initiate the inflammatory cascade causing end-organ injury at various sites such as the brain and lungs. C-reactive proteins cause lipid agglutination which may obstruct blood flow in the microvasculature. It also agglutinates chylomicrons, low-density lipoproteins, and the liposomes of nutritional fat emulsions. In addition, catecholamines release due to circulating FFAs increases further lipolysis. The mobilization and lysis of excess triglycerides lead to the incomplete binding to albumin and eventual triglyceride entry into the circulatory system forming fat globules. Agglutination of chylomicrons into fat globules is enhanced by various mediators such as catecholamines, FFAs, protein degradation products, and C-reactive proteins.[25],[26] FFAs have also been associated with cardiac dysfunction, a probable feature of FES.

This theory explains the delay in development of clinical FES from initiating events as onset of symptoms may coincide with the degradation and agglutination of fat and onset of inflammatory cascade. This theory also explains the development of nontraumatic FES. This theory is further supported by animal studies which reported that neutral fat does not injure the lung; however, if it is hydrolyzed over the course of hours to several products, including FFAs, it may cause ALI or acute respiratory distress syndrome (ARDS).[27]

Hence, from these different theories development of FES can be explained in two different phases, the first phase “Mechanical Phase” and the second phase “Biochemical Phase.”


  Clinical Presentation and Diagnostic Criteria Top


FES is purely a clinical diagnosis. It usually occurs in the second and third decade of life and typically presents 24–72 h after the initiating injury. Rarely, cases can occur as early as 12 h or as later as 2 weeks.[28] Patients of FES typically present with a clinical triad of pulmonary involvement, neurological involvement, and dermatological involvement.

Hypoxia is the most common clinical presentation, and very often, it is presented an hour before the onset of other clinical symptoms.[29] Other manifestations of pulmonary involvement include tachypnea, dyspnea, and cyanosis and may lead to respiratory failure in 10% of the cases. This clinical picture must be distinguished from pneumonia and acute respiratory distress syndrome (ARDS) or ALI. In most of the cases of FES, pulmonary involvement requires mechanical ventilation or positive end-expiratory pressure (PEEP) ventilation.[30]

Neurological features may be present either because of hypoxia or because of actual injury to brain parenchyma by circulating fat globules. Neurological involvement often occurs after the involvement of the respiratory system and is seen in up to 86% of the cases.[31] Often patients with neurological symptoms present in a state of acute confusion, but it can vary from mild confusion to severe seizures and a level of altered consciousness. Various neurological features described in multiple studies are irritability, anxiety, agitation, confusion, drowsiness, delirium, convulsions, coma, hypertonia, rigidity, and decerebration.[6],[9],[27],[29] Focal neurological manifestations such as anisocoria, aphasia, apraxia, hemiplegia, paraplegia, tetraplegia, scotomas, and eye conjugate deviation although less common but have been reported. Almost all neurological deficits are transient and completely reversible most of the times.[19],[32],[33],[34]

Dermatological involvement with characteristic petechial rashes constitutes the last component of the FES clinical triad. These are noticed in up to 60% of cases and can be seen in the conjunctiva, oral mucous membrane, and skin folds of the upper body, especially the neck and axilla. It is observed that petechial rashes do not appear because of abnormality in platelet functions but appears as a result of embolization of small dermal capillaries leading to extravasation of erythrocytes.[35] Typical petechial rashes usually appear within the first 36 h of development of FES and disappear completely within 7 days.

Meningococcal septicemia should be ruled out in differential diagnosis of other clinical signs may be present due to released toxic mediators due to initial injury or dysfunctional metabolism. These may include pyrexia, tachycardia, myocardial depression, electrocardiogram (ECG) changes suggestive of right heart strain, Purtscher's retinopathy, coagulation abnormalities as in disseminated intravascular coagulopathy (DIC), and kidney involvement presenting as oliguria, lipiduria, proteinuria, or hematuria.[35],[36],[37],[38]

As described earlier that FES is purely a clinical diagnosis; various clinical manifestations (respiratory failure, neurological features, and petechial rashes) are not pathognomic of FES as it may be seen in other polytrauma patients and also various laboratory tests and imaging findings are nonspecific, so various diagnostic criteria were given time to time for making the diagnosis of FES. Gurd and Wilson proposed clinical criteria for diagnosing FES [Table 2].[29] Lindeque proposed a diagnostic criteria for FES based only on the respiratory status of the patient [Table 3].[39]
Table 2: Gurd and Wilson's criteria

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Table 3: Lindeque's criteria

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More recently, Schonfeld proposed FE Index for diagnosing FES which is a quantitative measure comprised of seven clinical features, each one is given a particular score and a score of >5 is required for making the diagnosis of FES [Table 4].[40]
Table 4: Schonfeld's criteria

Click here to view


Diagnosis of FES is usually made on the basis of clinical findings, but biochemical investigations are also of value.


  Laboratory Investigations and Imaging Techniques Top


As emphasized earlier, various laboratory changes are typical of FES, they are not unique or diagnostic of this syndrome. Anemia, thrombocytopenia, coagulopathies, decrease in hematocrit, and increase in erythrocyte sedimentation rate various nonspecific findings which occur within 24–42 h and attributed to intraalveolar hemorrhage. It is well known that decrease in hematocrit is most common manifestation after a severe trauma, but it usually reaches at its lowest within 1–2 days of trauma and then become stable but a sudden drop in hematocrit after this may be contributed by pulmonary hemorrhages secondary to fatty acids toxicity. Thrombocytopenia is also a feature of FES which can be noted in about 30% of cases.[31] Cases of FES may present laboratory changes similar to DIC and changes often described are reduction of serum calcium and platelets, increase of platelet adherence, prolonged times of activated partial prothrombin and thromboplastin, release of FDPs (fibrin degradation products), and reduction of circulating fibrinogen.[29],[31],[41] As complement cascade have been suspected to be involved in the pathogenesis of FES due to activation of inflammatory cascade, so various laboratory investigations can detect the increase in complement activity; however, it is nonspecific and found in a lot of clinical conditions. An increase in serum level of FFAs, triglycerides, and AGLs is also noticed. These circulating AGLs are bonded to albumin molecules, so decrease in serum level of albumin may also be noticed. Although the most common pattern is the increase of circulating AGL after severe orthopedic injuries, serum levels of AGL have not been correlated to diagnosis or severity grading of FES.[41],[42] It is also noticed in various studies that the levels of lipase enzyme are increased between the 3rd and 5th day after trauma reaching their peaks around the 8th day, but it also lack diagnostic importance in FES.[41],[43] Fat droplets in the blood, urine, and sputum either in free form or inside the macrophages detected with Sudan or Oil Red O staining are noticed in FES, but these findings are also insensitive. It is a very common misconceptions that finding of fat globule in urine, sputum, or blood obtained from wedge pulmonary artery catheter is necessary for diagnosing FES, but in fact, their presence is of uncertain significance because we discussed at the beginning that presence of fat globules in urine or blood define FE, but it does not conclude FES diagnosis since majority of patients of FE do not progress with clinical features of this syndrome.[4],[5],[31] Although early detection of FES may be done by preliminary investigations for the presence of fat globules in pulmonary capillary blood obtained from a wedged pulmonary artery catheter.[44] Fat droplets may also be noticed in bronchoalveolar lavage but its use to aid in the diagnosis or to predict the likelihood of FES is still controversial due to its presence even in patients with sepsis, hyperlipidemia, or in patients on lipid infusions.[45] Arterial blood gas analysis (ABG) with an unexplained increase in pulmonary shunt fraction and an alveolar-to-arterial oxygen tension difference within 24–48 h of trauma is strongly suggestive of FES. ABG will demonstrate hypoxia, with a PaO2 of <60 mmHg along with the hypocapnia. Therefore, monitoring of arterial gases and of transcutaneous arterial saturation of hemoglobin are extremely important measures for follow-up of newly hospitalized FES-suspected patients.[41],[46],[47]

Chest radiography is the initial basic imaging modality and is mandatory in cases of trauma patients. It is found often normal initially but certain findings may be observed in FES in 30%–50% of cases such as diffuse bilateral pulmonary infiltrates, snow-storm' appearance, increased bronchovascular markings, and dilatation of the right side of the heart, but these findings cannot be considered as pathognomic of FES because these can also be noticed in cases of pulmonary congestion, pulmonary contusion, tracheobronchial aspiration of gastric contents, or ARDS.[48],[49]

Pulmonary ventilation/perfusion imaging may be executed for the suspicion of FES but findings from this imaging may be normal or may demonstrate a mottled pattern of subsegmental perfusion defects.

Spiral chest computerized tomography scan (CT-scan) may be found normal or may demonstrate focal areas of ground-glass opacities with interlobular septal thickening, centrilobular or subpleural nodules or parenchymal changes similar lung contusion, ALI, or adult respiratory distress syndrome (ARDS).[44]

CT scan of the head although represents a valuable test in many neurological conditions, but it does not add value to the diagnosis of FES and may be found normal. However, it may be used to rule out the cranial trauma or other head injuries which may deteriorate consciousness level. CT scan of the head may reveal diffuse white matter petechial hemorrhages because of microvascular injury of brain parenchyma.[50]

Magnetic resonance imaging (MRI) brain is more sensitive than CT scan and demonstrates earlier and specific damage to brain parenchyma because of circulating fat microemboli. The typical findings of MRI in FES are the low-intensity signs at T1 and high-intensity signs at T2 imaging. Characteristically, cerebral FES lesions are always located in the deep white substance of the basis, brainstem, and cerebellum ganglia. MRI of the brain may also reveal multiple hyperintense punctate lesions disseminated throughout the cerebral white matter on T2-weighted axial images and a so-called starfield pattern on diffusion-weighted images.[34],[51]

Transcranial Doppler sonography may indirectly reveal the most common lesion in cerebral FES that is perivascular edema by its ability detect the slowness of cerebral blood flow secondary to the increase of vascular resistance.[50]

ECG may reveal signs suggestive of the right-sided heart strain.[52],[53]

Intraoperative TEE may be helpful in evaluation of release of bone marrow contents in the bloodstream during intramedullary reaming of the long bones. The density of the echogenic substances going through the right atrium and ventricle of the heart correlates with the level of reduction in arterial oxygen saturation.[54]

As should have been obvious, with respect to what we have evaluated up until now, there is neither pathognomonic clinical picture nor an investigation facility that could close a demonstrative of FES. FES analysis depends, accordingly, on an entire informational collection, and history, signs and symptoms, and imaging tests ought to be constantly considered.


  Treatment and Prevention Top


There is no specific treatment modality for the management of FES; however, early diagnosis, continuous monitoring, supportive treatment, and prevention are the mainstay of treatment. As discussed earlier, hypoxia is the most common and earliest feature of FES, continuous pulse oximetry monitoring in the high-risk patients may help in detecting desaturation early allowing early identification of problem and institution of preventive or supportive measures.

Supportive therapy constitutes the mainstay of treatment as no specific treatment modality is available. It constitutes the early management of shock by volume resuscitation with crystalloid fluids or blood, mechanical ventilation and PEEP for maintenance of adequate oxygenation and ventilation, maintenance of stable hemodynamics, use of vasoactive drugs for maintenance of cardiac output and to decrease the preload on the heart, prophylaxis of deep vein thrombosis and stress-related gastrointestinal bleeding, and maintenance of adequate nutrition.[55] FES affects pulmonary functions severely, however, patients responding great to mechanical ventilation, the inflammatory process of FES is generally settled inside 3–7 days.[5]

Historically, various drugs were instituted in patients of FES as specific pharmacotherapy for management of FES but none show promising results. Ethyl alcohol showed the ability of reducing serum lipase activity and consequently reducing the release of FFAs in circulation and thus indicated as treatment of FES but no useful results were obtained.[56] Hypertonic glucose was also tried as 50 g oral or intravenous (IV) infusion as it reduces the concentration of FFAs within 30 min but results were still disputable.[57],[58] Dextran-40 was also introduced as pharmacotherapy of FES because of the idea that by promoting hemodilution, it would reduce the aggregation of platelets and erythrocytes. Even though its utilization was appeared to be valuable in keeping up or recuperating volemia in polytraumatic patients, no advantage was indicated with respect to incidence reduction or patients' advancement, and its utilization for these reasons was soon left aside. Although its use was shown to be useful in maintaining or recovering volemia in polytraumatic patients, no benefit was shown regarding incidence reduction of FES or patients' evolution and its use for these purposes was soon left aside.[57],[59],[60] Heparin was initially thought of some importance in treatment of FES as it stimulates the lipase and reverses lipemia, but it causes an undesirable increase of circulating fatty acids and creates a high risk of hemorrhage in polytraumatic patients, and hence, it became formally contraindicated for FES treatment.[61],[62],[63]

In the past, FES therapy was targeted toward reduction of lipemia and coagulation changes but today treatment targets the maintenance of oxygen levels and the cardiac output.[64]

Recently, use of human albumin IV was found to reduce the incidence and severity of FES occurring in orthopedic surgeries because of its FFA-chelating property and thus avoiding their toxicity.[65] In light of this evidence, the utilization of albumin IV was proposed and tried for FES treatment, yet it has not been embraced because of the absence of noteworthy evidence. Aprotinin (Trasylol) is also being tried for management of FES because of its platelets aggregation inhibiting, serotonin release reducing, and proteases actions blocking property.[66] Recently, Aspirin has also been used for the management of FES due to some of its beneficial effects in patients of FES.[5],[31] Corticosteroids mainly methylprednisolone are also considered for treatment of FES because of their anti-inflammatory actions both local and systemic (inhibiting the release of proteolytic enzymes of neutrophils', lysosomes, complement activation, systemic inflammatory response, and platelet aggregation), but their efficacy is considered of no more use in the treatment of FES. However, methylprednisolone use shows promising results for the prophylaxis of FES and reducing the severity and mortality of FES.[39],[40],[67]

Preventive measures

Early immobilization of the fractures of long bone and pelvis decreases the occurrence of FES. The hazard is additionally diminished by operative intervention, as opposed to nonoperative management.[68] External fixator application or open reduction and internal fixation with plates and screws produces lesser lung injury than nailing the medullary canal.[69] Constraining the rise of intraosseous pressure during orthopedic procedures likewise prevent FE disorder by decreasing the intravasation of intramedullary fat and different debris material.[70],[71],[72],[73],[74] Various modifications have been described during orthopedic surgeries as preventive measures to reduce to the incidence and severity of FES such as cleaning of the medullary cavity with saline solution, followed by aspiration of medullary content, use of fluted intramedullary rods in place of cylindrical rods, overdrilling of entrance port, distal venting by performing a 4–6 cm hole in diaphysis distal to prosthesis, retrograde filling of medullary cavity with cement, using low viscosity cement, using proximal vacuum, using prosthesis without cement, use of narrow reamers, slow insertion of nail, unreamed intramedullary femoral shaft stabilization in patients with associated chest injuries, and use of reamer irrigator aspirator devices.[68],[70],[71],[72],[73],[74],[75],[76],[77],[78],[79],[80],[81]

Corticosteroids prophylaxis

Due to low incidence, unclear risk factors, low mortality, and a good outcome with conservative management, corticosteroid prophylaxis is controversial, but a number of studies report decreased incidence and severity of FES when corticosteroids were given prophylactically as also no complications related to use of corticosteroids observed.[39],[40] Today's rationale would be to give prophylactic steroid therapy only to those patients at high risk for FES, and for this, methylprednisolone 1.5 mg/kg IV can be administered every 8 h for six doses.[82]

Prophylactic placement of the inferior vena cava filters has been advocated as a method to reduce the volume of fat that reaches to the heart and lungs and thus decreasing the chances of FES but this has not been adequately studied and there is a paucity of literature.[83] Moreover, risk of the surgery for placing inferior vena cava filters should be weight against benefits.

Hyperbaric oxygen (HBO) therapy is defined by the Undersea and Hyperbaric Medical Society as a treatment in which a patient intermittingly breathes 100% oxygen under a pressure that is greater than the pressure at sea level.[84] Adequacy of early HBO treatment on cerebral FE has been affirmed. It expands blood oxygen pressure and oxygen content and in addition outspread dissemination of oxygen in the brain capillaries to enhance microcirculation. It likewise stimulates growth of capillaries which helps in establishing collateral circulation.[85]


  Conclusion Top


Most patients with FES recover fully without residual deficits. Mortality rate varies from 5% to 15% in various studies. However, patients with older age, numerous comorbid medical conditions, and diminished physiologic reserve have more terrible results. The fulminant form of FES displays as acute cor pulmonale, respiratory failure or embolism, and prompting to death of patient inside few hours of injury.

Hence in short, a high index of suspicion is needed to diagnose FES and a combination of clinical criteria is needed to accurately diagnose it and early supportive therapy is the mainstay of treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Akoh CC, Schick C, Otero J, Karam M. Fat embolism syndrome after femur fracture fixation: A case report. Iowa Orthop J 2014;34:55-62.  Back to cited text no. 1
    
2.
George J, George R, Dixit R, Gupta RC, Gupta N. Fat embolism syndrome. Lung India 2013;30:47-53.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg 1997;132:435-9.  Back to cited text no. 3
    
4.
Fabian TC, Hoots AV, Stanford DS, Patterson CR, Mangiante EC. Fat embolism syndrome: Prospective evaluation in 92 fracture patients. Crit Care Med 1990;18:42-6.  Back to cited text no. 4
    
5.
Mellor A, Soni N. Fat embolism. Anaesthesia 2001;56:145-54.  Back to cited text no. 5
    
6.
Levy D. The fat embolism syndrome. A review. Clin Orthop Relat Res 1990;261:281-6.  Back to cited text no. 6
    
7.
Shapiro MP, Hayes JA. Fat embolism in sickle cell disease. Report of a case with brief review of the literature. Arch Intern Med 1984;144:181-2.  Back to cited text no. 7
    
8.
Dillerud E. Abdominoplasty combined with suction lipoplasty: A study of complications, revisions, and risk factors in 487 cases. Ann Plast Surg 1990;25:333-8.  Back to cited text no. 8
    
9.
Johnson MJ, Lucas GL. Fat embolism syndrome. Orthopedics 1996;19:41-8.  Back to cited text no. 9
    
10.
Svenningsen S, Nesse O, Finsen V, Hole A, Benum P. Prevention of fat embolism syndrome in patients with femoral fractures – Immediate or delayed operative fixation? Ann Chir Gynaecol 1987;76:163-6.  Back to cited text no. 10
    
11.
Pinney SJ, Keating JF, Meek RN. Fat embolism syndrome in isolated femoral fractures: Does timing of nailing influence incidence? Injury 1998;29:131-3.  Back to cited text no. 11
    
12.
Pell AC, Christie J, Keating JF, Sutherland GR. The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. A study of 24 patients with femoral and tibial fractures. J Bone Joint Surg Br 1993;75:921-5.  Back to cited text no. 12
    
13.
Gauss H. The pathology of fat embolism. Arch Surg 1924;9:592-605.  Back to cited text no. 13
    
14.
Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR, et al. Brief report: Fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med 1993;329:926-9.  Back to cited text no. 14
    
15.
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 2001;92:49-55.  Back to cited text no. 15
    
16.
Aoki N, Soma K, Shindo M, Kurosawa T, Ohwada T. Evaluation of potential fat emboli during placement of intramedullary nails after orthopedic fractures. Chest 1998;113:178-81.  Back to cited text no. 16
    
17.
Parker RI. Coagulation disorders. In: Civetta JM, Taylor RW, Kirby RR, editors. Critical Care. 3rd ed. Philadelphia: Lippincott-Raven; 1997. p. 2217-30.  Back to cited text no. 17
    
18.
Parmet JL, Horrow J, Rosenberg H. Fat embolism syndrome. N Engl J Med 1994;330:642-3.  Back to cited text no. 18
    
19.
Estèbe JP. From fat emboli to fat embolism syndrome. Ann Fr Anesth Reanim 1997;16:138-51.  Back to cited text no. 19
    
20.
Sulek CA, Davies LK, Enneking FK, Gearen PA, Lobato EB. Cerebral microembolism diagnosed by transcranial Doppler during total knee arthroplasty: Correlation with transesophageal echocardiography. Anesthesiology 1999;91:672-6.  Back to cited text no. 20
    
21.
Schemitsch EH, Jain R, Turchin DC, Mullen JB, Byrick RJ, Anderson GI, et al. Pulmonary effects of fixation of a fracture with a plate compared with intramedullary nailing. A canine model of fat embolism and fracture fixation. J Bone Joint Surg Am 1997;79:984-96.  Back to cited text no. 21
    
22.
Lovering AT, Romer LM, Haverkamp HC, Pegelow DF, Hokanson JS, Eldridge MW, et al. Intrapulmonary shunting and pulmonary gas exchange during normoxic and hypoxic exercise in healthy humans. J Appl Physiol (1985) 2008;104:1418-25.  Back to cited text no. 22
    
23.
Gossling HR, Ellison LH, Degraff AC Jr. Fat embolism. The role of respiratory failure and its treatment. J Bone Joint Surg Am 1974;56:1327-37.  Back to cited text no. 23
    
24.
Lehman EP. Fat embolism, including experimental production without trauma. Arch Surg 1927;14:621-62.  Back to cited text no. 24
    
25.
ten Duis HJ. The fat embolism syndrome. Injury 1997;28:77-85.  Back to cited text no. 25
    
26.
Hulman G. Fat macroglobule formation from chylomicrons and non-traumatic fat embolism. Clin Chim Acta 1988;177:173-8.  Back to cited text no. 26
    
27.
Hulman G. Pathogenesis of non-traumatic fat embolism. Lancet 1988;1:1366-7.  Back to cited text no. 27
    
28.
Carr JB, Hansen ST. Fulminant fat embolism. Orthopedics 1990;13:258-61.  Back to cited text no. 28
    
29.
Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br 1974;56B: 408-16.  Back to cited text no. 29
    
30.
King MB, Harmon KR. Unusual forms of pulmonary embolism. Clin Chest Med 1994;15:561-80.  Back to cited text no. 30
    
31.
Capan LM, Miller SM, Patel KP. Fat embolism. Anesthesiol Clin North Am 1993;11:25-54.  Back to cited text no. 31
    
32.
Byrick RJ. Fat embolism and postoperative coagulopathy. Can J Anaesth 2001;48:618-21.  Back to cited text no. 32
    
33.
Jacobson DM, Terrence CF, Reinmuth OM. The neurologic manifestations of fat embolism. Neurology 1986;36:847-51.  Back to cited text no. 33
    
34.
Kamano M, Honda Y, Kitaguchi M, Kazuki K. Cerebral fat embolism after a nondisplaced tibial fracture: Case report. Clin Orthop Relat Res 2001;389:206-9.  Back to cited text no. 34
    
35.
Kaplan RP, Grant JN, Kaufman AJ. Dermatologic features of the fat embolism syndrome. Cutis 1986;38:52-5.  Back to cited text no. 35
    
36.
Murray DA, Racz GB. Fat embolism syndrome: A rational for treatment. J Bone Joint Surg Br 1974;56:1338-49.  Back to cited text no. 36
    
37.
Jones JP Jr. Fat embolism, intravascular coagulation, and osteonecrosis. Clin Orthop Relat Res 1993;292:294-308.  Back to cited text no. 37
    
38.
Gitin TA, Seidel T, Cera PJ, Glidewell OJ, Smith JL. Pulmonary microvascular fat: The significance? Crit Care Med 1993;21:673-7.  Back to cited text no. 38
    
39.
Lindeque B, Schoeman H, Dommisse G, Boeyens MC, Vlok AL. Fat embolism and the fat embolism syndrome. J Bone Joint Surg 1987;69B: 128-31.  Back to cited text no. 39
    
40.
Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammerschmidt DE, et al. Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients. Ann Intern Med 1983;99:438-43.  Back to cited text no. 40
    
41.
Riseborough EJ, Herndon JH. Alterations in pulmonary function, coagulation and fat metabolism in patients with fractures of the lower limbs. Clin Orthop Relat Res 1976;115:248-67.  Back to cited text no. 41
    
42.
Nixon JR, Brock-Utne JG. Free fatty acid and arterial oxygen changes following major injury: A correlation between hypoxemia and increased free fatty acid levels. J Trauma 1978;18:23-6.  Back to cited text no. 42
    
43.
Peltier LF, Adler F, Lai SP. Fat embolism: The significance of an elevated serum lipase after trauma to bone. Am J Surg 1960;99:821-6.  Back to cited text no. 43
    
44.
Van den Brande FG, Hellemans S, De Schepper A, De Paep R, Op De Beeck B, De Raeve HR, et al. Post-traumatic severe fat embolism syndrome with uncommon CT findings. Anaesth Intensive Care 2006;34:102-6.  Back to cited text no. 44
    
45.
Vedrinne JM, Guillaume C, Gagnieu MC, Gratadour P, Fleuret C, Motin J, et al. Bronchoalveolar lavage in trauma patients for diagnosis of fat embolism syndrome. Chest 1992;102:1323-7.  Back to cited text no. 45
    
46.
Lindeque BG, Schoeman HS, Dommisse GF, Boeyens MC, Vlok AL. Fat embolism and the fat embolism syndrome. A double-blind therapeutic study. J Bone Joint Surg Br 1987;69:128-31.  Back to cited text no. 46
    
47.
Burnstein RM, Newell JP, Jones JG. Sequential changes in gas exchange following traumatic fat embolism. Anaesthesia 1998;53:373-8.  Back to cited text no. 47
    
48.
Muangman N, Stern EJ, Bulger EM, Jurkovich GJ, Mann FA. Chest radiographic evolution in fat embolism syndrome. J Med Assoc Thai 2005;88:1854-60.  Back to cited text no. 48
    
49.
Eriksson EA, Schultz SE, Cohle SD, Post KW. Cerebral fat embolism without intracardiac shunt: A novel presentation. J Emerg Trauma Shock 2011;4:309-12.  Back to cited text no. 49
[PUBMED]  [Full text]  
50.
Satoh H, Kurisu K, Ohtani M, Arita K, Okabayashi S, Nakahara T, et al. Cerebral fat embolism studied by magnetic resonance imaging, transcranial Doppler sonography, and single photon emission computed tomography: Case report. J Trauma 1997;43:345-8.  Back to cited text no. 50
    
51.
Takahashi M, Suzuki R, Osakabe Y, Asai JI, Miyo T, Nagashima G, et al. Magnetic resonance imaging findings in cerebral fat embolism: Correlation with clinical manifestations. J Trauma 1999;46:324-7.  Back to cited text no. 51
    
52.
Gossling HR, Pellegrini VD Jr. Fat embolism syndrome: A review of the pathophysiology and physiological basis of treatment. Clin Orthop Relat Res 1982;165:68-82.  Back to cited text no. 52
    
53.
Forteza AM, Koch S, Romano JG, Zych G, Bustillo IC, Duncan RC, et al. Transcranial Doppler detection of fat emboli. Stroke 1999;30:2687-91.  Back to cited text no. 53
    
54.
Wenda K, Runkel M, Degreif J, Ritter G. Pathogenesis and clinical relevance of bone marrow embolism in medullary nailing – Demonstrated by intraoperative echocardiography. Injury 1993;24 Suppl 3:S73-81.  Back to cited text no. 54
    
55.
Richards RR. Fat embolism syndrome. Can J Surg 1997;40:334-9.  Back to cited text no. 55
    
56.
Myers R, Taljaard JJ. Blood alcohol and fat embolism syndrome. J Bone Joint Surg Am 1977;59:878-80.  Back to cited text no. 56
    
57.
Horne RH, Horne JH. Fat embolism prophylaxis: Use of hypertonic glucose. Arch Intern Med 1974;133:288.  Back to cited text no. 57
    
58.
Stoltenberg JJ, Gustilo RB. The use of methylprednisolone and hypertonic glucose in the prophylaxis of fat embolism syndrome. Clin Orthop Relat Res 1979;143:211-21.  Back to cited text no. 58
    
59.
Filomena LT, Carelli CR, Figueirdo da Silva NC, Pessoa de Barros Filho TE, Amatuzzi MM. Fat embolism: A review for current orthopaedics Practice. Acta Ortop Bras 2005;13:196-208.  Back to cited text no. 59
    
60.
Freeman JI, Enneking FK. Orthopedic complications. In: Civetta JM, Taylor RW, Kirby RR, editors. Critical Care. 3rd ed. Philadelphia: Lippincot-Raven; 1996. p. 1231-52.  Back to cited text no. 60
    
61.
Ross AP. The value of serum lipase estimations in the fat embolism syndrome. Surgery 1969;65:271-3.  Back to cited text no. 61
    
62.
Scroggins C, Barson PK. Fat embolism syndrome in a case of abdominal lipectomy with liposuction. Md Med J 1999;48:116-8.  Back to cited text no. 62
    
63.
King EG, Weily HS, Genton E, Ashbaugh DG. Consumption coagulopathy in the canine oleic acid model of fat embolism. Surgery 1971;69:533-41.  Back to cited text no. 63
    
64.
Murray DG, Racz GB. Fat-embolism syndrome (respiratory insufficiency syndrome). A rationale for treatment. J Bone Joint Surg Am 1974;56:1338-49.  Back to cited text no. 64
    
65.
Hofman WF, Ehrhart IC. Albumin attenuation of oleic acid edema in dog lung depleted of blood components. J Appl Physiol (1985) 1985;58:1949-55.  Back to cited text no. 65
    
66.
Sari A, Miyauchi Y, Yamashita S, Yokota K, Ogasahara H, Yonei A, et al. The magnitude of hypoxemia in elderly patients with fractures of the femoral neck. Anesth Analg 1986;65:892-4.  Back to cited text no. 66
    
67.
Shivaprakash SS, Sen RK. Steroids in the Prophylaxis of Fat Embolism Syndrome. 2012;1:381. doi:10.4172/scientificreports.381.  Back to cited text no. 67
    
68.
Behrman SW, Fabian TC, Kudsk KA, Taylor JC. Improved outcome with femur fractures: Early vs. delayed fixation. J Trauma 1990;30:792-7.  Back to cited text no. 68
    
69.
Wheelwright EF, Byrick RJ, Wigglesworth DF, Kay JC, Wong PY, Mullen JB, et al. Hypotension during cemented arthroplasty. Relationship to cardiac output and fat embolism. J Bone Joint Surg Br 1993;75:715-23.  Back to cited text no. 69
    
70.
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 1999;119:146-50.  Back to cited text no. 70
    
71.
Pitto RP, Koessler M, Kuehle JW. Comparison of fixation of the femoral component without cement and fixation with use of a bone-vacuum cementing technique for the prevention of fat embolism during total hip arthroplasty. A prospective, randomized clinical trial. J Bone Joint Surg Am 1999;81:831-43.  Back to cited text no. 71
    
72.
Kröpfl A, Davies J, Berger U, Hertz H, Schlag G. Intramedullary pressure and bone marrow fat extravasation in reamed and unreamed femoral nailing. J Orthop Res 1999;17:261-8.  Back to cited text no. 72
    
73.
Kim YH, Oh SW, Kim JS. Prevalence of fat embolism following bilateral simultaneous and unilateral total hip arthroplasty performed with or without cement: A prospective, randomized clinical study. J Bone Joint Surg Am 2002;84-A: 1372-9.  Back to cited text no. 73
    
74.
Pitto RP, Hamer H, Fabiani R, Radespiel-Troeger M, Koessler M. Prophylaxis against fat and bone-marrow embolism during total hip arthroplasty reduces the incidence of postoperative deep-vein thrombosis: A controlled, randomized clinical trial. J Bone Joint Surg Am 2002;84-A: 39-48.  Back to cited text no. 74
    
75.
Pape HC, Giannoudis PV, Krettek C, Trentz O. Timing of fixation of major fractures in blunt polytrauma: Role of conventional indicators in clinical decision making. J Orthop Trauma 2005;19:551-62.  Back to cited text no. 75
    
76.
Cox G, Tzioupis C, Calori GM, Green J, Seligson D, Giannoudis PV, et al. Cerebral fat emboli: A trigger of post-operative delirium. Injury 2011;42 Suppl 4:S6-10.  Back to cited text no. 76
    
77.
Müller C, Frigg R, Pfister U. Effect of flexible drive diameter and reamer design on the increase of pressure in the medullary cavity during reaming. Injury 1993;24 Suppl 3:S40-7.  Back to cited text no. 77
    
78.
Richards JE, Guillamondegui OD, Archer KR, Jackson JC, Ely EW, Obremskey WT, et al. The association of reamed intramedullary nailing and long-term cognitive impairment. J Orthop Trauma 2011;25:707-13.  Back to cited text no. 78
    
79.
Volgas DA, Burch T, Stannard JP, Ellis T, Bilotta J, Alonso JE, et al. Fat embolus in femur fractures: A comparison of two reaming systems. Injury 2010;41 Suppl 2:S90-3.  Back to cited text no. 79
    
80.
Dorr LD, Merkel C, Mellman MF, Klein I. Fat emboli in bilateral total knee arthroplasty. Predictive factors for neurologic manifestations. Clin Orthop Relat Res 1989;248:112-8.  Back to cited text no. 80
    
81.
Byrick RJ, Bell RS, Kay JC, Waddell JP, Mullen JB. High-volume, high-pressure pulsatile lavage during cemented arthroplasty. J Bone Joint Surg Am 1989;71:1331-6.  Back to cited text no. 81
    
82.
Kallenbach J, Lewis M, Zaltzman M, Feldman C, Orford A, Zwi S, et al. ‘Low-dose’ corticosteroid prophylaxis against fat embolism. J Trauma 1987;27:1173-6.  Back to cited text no. 82
    
83.
Kwiatt ME, Seamon MJ. Fat embolism syndrome. Int J Crit Illn Inj Sci 2013;3:64-8.  Back to cited text no. 83
[PUBMED]  [Full text]  
84.
Calvert JW, Cahill J, Zhang JH. Hyperbaric oxygen and cerebral physiology. Neurol Res 2007;29:132-41.  Back to cited text no. 84
    
85.
Zhou Y, Yuan Y, Huang C, Hu L, Cheng X. Pathogenesis, diagnosis and treatment of cerebral fat embolism. Chin J Traumatol 2015;18:120-3.  Back to cited text no. 85
    



 
 
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