International Journal of Research in Medical Sciences

Shafi A et al. Int J Res Med Sci. 2022 Sep;10(9):2005-2010

www.msjonline.org

pISSN 2320-6071 | eISSN 2320-6012

Case Series

DOI: https://dx.doi.org/10.18203/2320-6012.ijrms20222279

Fat embolism syndrome: a case series and review of literature

Aamir Shafi1*, Tahir Ashraf Kar1, Asif Bashir Thoker2, Aariba Zahoor1

1Department of General Medicine, 2Department of Orthopaedics, SKIMS Medical College and Hospital, Bemina Srinagar, Jammu and Kashmir, India

Received: 30 June 2022

Revised: 28 July 2022

Accepted: 01 August 2022

*Correspondence:

Dr. Aamir Shafi,

E-mail: amirshafi400@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Fat embolism and fat embolism syndrome (FES) is a clinical spectrum characterized by dissemination of fat emboli into the systematic circulation usually as a result of orthopedic trauma and related surgical procedures. we present a case series of three patients who had FES of variable presentation and severity. In our first case patient initially developed FES pre operatively which was complicated by acute pulmonary thromboembolism in the post operative period. In our third case patient developed FES after intra medullary nail fixation of femoral shaft fracture. Fat embolism is relatively rare but fatal complication in orthopedic trauma and during long bone fracture manipulations. In addition, fat embolism is a risk factor for pulmonary thromboembolism as was evident in our first case. So, patients of fat embolism should be closely monitored for the later. Gurd and Wilson are the most commonly used criteria for the diagnosis of FES. Treatment is largely supportive and some preventive measures include early fixation of long bone fractures. Prophylactic use of steroids in a meta-analysis has been found to prevent occurrence of FES in nearly two third of patients. There is no proven role of hypertonic dextrose infusion, heparin or corticosteroids in the treatment of FES and therefore are not routinely recommended. In case of fulminant FES steroids should be considered.

Keywords: Fat embolism syndrome, Long bone fracture, Gurd and Wilson criteria

INTRODUCTION

Fat embolism syndrome (FES) occurs in 0.5-11% of the patients with a mortality of 7-10%. There is increased incidence of pulmonary thromboembolism in these patents. The first clinical presentation of FES was described by Zenker after a patient suffered a crush injury. The clinical diagnosis of this condition was given by Von Bergman.1,2 Finally in early 70’s the clinical criterion for the diagnosis of fat embolism was proposed by Gurd and final modification was done by Wilson in 1974 and established a combined Gurd and Wilson criteria which is most commonly used in clinical practice.3-5 Although this criterion helps in the diagnosis of FES it still remains a diagnostic challenge for majority of the clinicians.

The most commonly used clinical trial of FES includes central nervous system (CNS) manifestations, respiratory failure and skin rash.4,5 Petechial rash occurs in 50-60% of the patients, lasting transiently for 4-6 hours usually seen on anterior thorax and axillae.6,7 Retinal lesions occurs in 50% of the patients, are self-limiting and usually disappear within weeks. There occurs an asymptomatic interval of 12-72 hours after initial injury. The highest incidence is seen in 10-40-years age group with slightly higher incidence in males.8,9

CASE SERIES

Case 1

A 23-year-old young healthy female was brought to orthopedic emergency department with history of road traffic accident. On assessment she had closed bilateral femoral shaft fractures (Figure 1). The fractures were immediately splinted and she was admitted for definitive fixation. 48 hours after admission she developed sudden and progressive shortness of breath and hypoxia with an oximetric saturation of 75% on ambient air, requiring fraction of inspired oxygen (FiO2) of 60% to maintain saturation of >94%. There was no altered sensorium, truncal rash, vision abnormality but she was febrile, restless, tachycardic and in respiratory distress. Cheat X-ray was grossly normal.

Having suffered bilateral femoral shaft fracture and subsequent immobilization a possibility of fat embolism vs pulmonary embolism was made. Computed tomography pulmonary angiogram (CTPA) was done which showed ground glass opacities in bilateral lung fields more in the lower zones consistent with interstitial hemorrhage associated with fat embolism (Figure 1). Hemogram revealed drop of hemoglobin from 13 mg/dl to 11 mg/dl and thrombocytopenia. Erythrocyte sedimentation rate (ESR) was raised and serum fat macro globules were present fulfilling the Gurd and Wilson criteria for FES. She was managed in intensive care unit (ICU) with oxygen support, aggressive vital monitoring, deep vein thrombosis (DVT) prophylaxis and intravenous methylprednisolone.

She showed progressive improvement in her oxygen saturation over a period of five days and after achieving hemodynamic stability she was subjected to fixation of fractures under spinal anesthesia and immediate post-operative course remained uneventful.

Three days after internal fixation of fracture she again developed hypoxia and was tachycardic and tachypnoeic on clinical examination. There was no fever or any new infiltrates on chest X-ray. Qualifying as high risk on Well’s PTE score CTPA was done which showed thrombi in left interlobar artery and right lower lobe segmental branches (Figure 2). There was no hypotension or right ventricular strain on echocardiography and cardiac biomarkers were negative. She was started on rivaroxaban 15 mg BD. She showed improvement in oxygenation and was discharged after 15 days of complicated hospital course in hemodynamically stable condition on oral anticoagulation.

Figure 1: Shows ground glass opacities in bilateral lung fields (R>L).
Figure 1: Shows ground glass opacities in bilateral lung fields (R>L).
Figure 2: Depicting thrombus in (a) left interlobar artery, and (b) right lower lobe segmental artery.
Figure 2: Depicting thrombus in (a) left interlobar artery, and (b) right lower lobe segmental artery.

Case 2

A 45-year male was referred from a secondary care hospital with sudden onset breathlessness and altered mental status two days after suffering road traffic accident in which he fractured his left tibia. On examination he was agitated, pale and tachypnoeic. X-ray chest revealed no gross infilterates. CT scan of chest revealed bilateral ground glass opacities more in the lower lobes (Figure 3). Hemogram revealed anemia and thrombocytopenia with high ESR. He was managed as fat embolism syndrome (Gurd and Wilson criteria) by immediate fixation of tibial fracture along with oxygen support and other symptomatic treatment. The patient showed signs of recovery and was discharged home after one week in a hemodynamically stable condition.

Figure 3: Depicting groundglass opacities in bilateral lung fields.
Figure 3: Depicting groundglass opacities in bilateral lung fields.

Case 3

A 25-year-old male was admitted to our hospital after suffering a road traffic accident resulting in fracture shaft of femur. After stabilization fixation of the fracture was done by intramedullary nail (Figure 4). 12 hours after the procedure patient developed hypoxia and blood gas revealed type-I respiratory failure. Having normal chest X-ray and moderate probability for PTE as per Wells criteria CTPA was done which did not reveal any thrombus but showed bilateral interstitial infiltrates with areas of ground glassing. Although the patient did not fulfil diagnostic criteria for fess, he was managed on same lines in view of long bone fracture and intramedullary nailing. The patient showed full recovery over a period of one week.

Figure 4: Shows femoral shaft fracture fixated by intramedullary nail.
Figure 4: Shows femoral shaft fracture fixated by intramedullary nail.

DISCUSSION

FES is mostly commonly seen after orthopaedic trauma especially in a background of long bone closed fractures (case 1 and 2). It can also occur as a complication during orthopaedic surgery like after intramedullary nail fixation or manipulation of fracture sites (case 3). The incidence is 0.17% in isolated/multiple orthopaedic fractures, 0.54% in isolated femoral fractures and 1.29% in multiple fractures including femoral fractures.10 Asymptomatic fat embolism is seen in 82% of autopsy specimens. In patients who have received CPR asymptomatic fat embolism has been found in 88 of autopsy specimens.7 However, there are non-traumatic causes of FES which are rare but otherwise well established. These include acute or chronic pancreatitis, sickle cell crises, alcoholic liver diseases, bone marrow harvest/transplantation, liposuction, infusion of fat emulsion, steroids and lymphography.11

Pathophysiology

Two theories have been proposed to explain the pathophysiology of FES.

Mechanical theory

It was proposed by Gasling who suggested that fat cells after getting released from bone marrow mount a pro inflammatory cascade in addition to having a prothrombotic potential. After lodging in pulmonary circulation there occurs interstitial hemorrhage, edema, alveolar collapse resulting in reactive hypoxemic vasoconstriction. Massive fat embolism can lead to obstructive shock and even death mimicking a massive pulmonary thromboembolism.12-14

Biochemical theory

It was proposed by Baker et al it suggested that the fat released from the bone marrow into systemic circulation is lysed by serum lipases into glycerol and toxic free fatty acids which damage pneumocytes and endothelial cells with release of phospholipase A2, TNF alpha, interleukin 6 and CRP leading to ARDS.12-14

Clinical spectrum

The cardinal manifestations of FES include CNS, pulmonary and skin/integumentary disturbances. The CNS manifestations include agitation, anxiousness, restlessness and severe manifestations can be in the form of seizures and coma. Petechial rash is caused by post obstructive haemorrhage at capillary level. It is located in non-dependent regions like conjunctiva, head and neck, anterior thorax or axillae (Figure 5).15 Ocular manifestations include cotton wool spots, exudates, retinal haemorrhage and macular edema (Figure 6).16

Figure 5: Classical petechial rash on thorax and axilla in a patient with fat embolism syndrome.15
Figure 5: Classical petechial rash on thorax and axilla in a patient with fat embolism syndrome.15
Figure 6: Image of fundus showing cotton wool spots, macular edema and few superficial hemorrhages suggestive of ocular fat embolism syndrome.16
Figure 6: Image of fundus showing cotton wool spots, macular edema and few superficial hemorrhages suggestive of ocular fat embolism syndrome.16

Diagnosis

Following three set of criteria have been proposed for the diagnosis of FES of which Gurd and Wilson stands the most reliable and commonly used criteria (Table 1).17

Table 1: Diagnostic criteria for FES.
Table reproduced from source PDF page 4

ESR=Erythrocyte sedimentation rate, bpm= beats per minute, FES=fat embolism syndrome

Ancillary investigations

In addition to the above-mentioned criteria some ancillary investigations are recommended as a part of diagnostic workup of FES.

Haemogram reveals anemia and thrombocytopenia in two third of the patients. Biochemical parameters may reveal azotemia and metabolic acidosis. Arterial blood gas analysis reveals ventilation perfusion mismatch which is hallmark of FES. It also reveals low partial pressure of oxygen with increased A-a gradient.18

Imaging

Chest X-ray is grossly normal but can have florid presentation varying from bilateral lung infiltrates to a full-fledged pulmonary edema, diffused interstitial infiltrates and snow storm appearance (Figure 7).18,19

Figure 7: Chest X-ray showing bilateral diffuse infiltrates snow storm appearance.18
Figure 7: Chest X-ray showing bilateral diffuse infiltrates snow storm appearance.18

CT scan of chest

CT scan of the chest reveals areas of vascular congestion, crazy paving, ground glass opacities in geographic distribution with interlobular septal thickening, areas of consolidation and inflamed pulmonary lymph nodes or hemorrhage (Figure 8).20-23 CT imaging of brain has low sensitivity for fat embolism but is done to rule out alternative causes for altered mental status.

MRI of brain

MRI of the brain is most sensitive to reveal fat embolism related changes. The chief areas of brain which are involved are centrum semi ovale, sub cortical white matter, ganglionic regions and thalamus (Figure 9).24,31,32

Management

No definitive management till date has proven to decrease the mortality in FES. The treatment lies strictly on symptomatic care and intensive ventilatory support.28-30 Early fixation of fractures (<24 hours) has been found to prevent the occurrence of FES.28,29 External fixation should be attempted in high-risk patients.29 Hypertonic Dextrose infusion has been found to decrease free fatty acid mobilization. Ethanol has been tried due to its inhibitory effect on lypolysis but none of the above therapies has proved beneficial.30 Heparin is not recommended in view of bleeding risk.

Steroids

Steroids should be considered in case of fulminant FES. These work by inhibiting compliment activated leucocyte aggregation, limiting free fatty acids levels and membrane stabilization. Meta-analysis from seven randomized controlled trials have revealed that the use of prophylactic steroids with long bone fractures reduces the incidences of FES by 78%.27,28 The number needed to prevent one episode of FES was eight but large trials are needed to confirm the above findings. Some techniques which have been advocated to decrease the leakage of fat cells into systemic circulation but have not found beneficial in reducing the occurrence of FES are: bone marrow lavage prior to fixation, femoral bone venting, and creation of small holes by drilling the cortex of long bone to reduce intra medullary pressure.29

Figure 8: CT image of chest showing extensive bilateral crazy paving pattern more in perihilar regions.20
Figure 8: CT image of chest showing extensive bilateral crazy paving pattern more in perihilar regions.20
Figure 9: Fluid attenuated inversion recovery MR image of brain showing multiple focal lesions in periventricular and deep white matter characteristic of cerebral FES.24
Figure 9: Fluid attenuated inversion recovery MR image of brain showing multiple focal lesions in periventricular and deep white matter characteristic of cerebral FES.24

CONCLUSION

The mortality in FES ranges from 7-10% with some studies quoting up to 20%. The cause of mortality is usually ARDS followed by cerebral edema. Prognosis depends on early fixation of long bone fracture. Most of the patients who receive adequate supportive therapy show full recovery from respiratory, neurological and retinal complications. Our case series highlights the rare presentation of FES in which one patient (case 1) developed concomitant FES and acute PTE. Another patient (case 3) developed FES after fixation of fracture with intramedullary nail. Finally, these patients are at increased risk of pulmonary thromboembolism (case 1) and therefore close monitoring of hemodynamics and DVT prophylaxix should be strongly considered.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

  1. 1. Talbot M, Schemitsch EH. Fat embolism syndrome: history, definition, epidemiology. Injury. 2006; 37(4):S3-7.
  2. 2. 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.
  3. 3. Stein PD, Yaekoub AY, Matta F, Kleerekoper M. Fat embolism syndrome. Am J Med Sci. 2008;336:472-7.
  4. 4. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg. 1997;132:435-9.
  5. 5. Fukumoto LE, Fukumoto KD. Fat Embolism Syndrome. Nurs Clin North Am. 2018;53(3):335-47.
  6. 6. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg. 1997;132:435-9.
  7. 7. Eriksson EA, Pellegrini DC, Vanderkolk WE, Minshall CT, Fakhry SM, Cohle SD. Incidence of pulmonary fat embolism at autopsy: an undiagnosed epidemic. J Trauma. 2011;71:312-5.
  8. 8. Scarpino M, Lanzo G, Lolli F, Grippo A. From the diagnosis to the therapeutic management: cerebral fat embolism, a clinical challenge. Int J Gen Med. 2019;12:39-48.
  9. 9. Shaikh N, Mahmood Z, Ghuori SI, Chanda A, Ganaw A, Zeeshan Q, Ehfeda M, Mohamed Belkhair AO, Zubair M, Kazi ST, Momin U. Correlation of clinical parameters with imaging findings to confirm the diagnosis of fat embolism syndrome. Int J Burns Trauma. 2018;8(5):135-44.
  10. 10. Riska EB, Myllynen P. Fat embolism in patients with multiple injuries. J Trauma. 1982;22:891-4.
  11. 11. llardyce DB, Meek RN, Woodruff B, Cassim MM, Ellis D. Increasing our knowledge of the pathogenesis of fat embolism: A prospective study of 43 patients with fractured femoral shafts. J Trauma. 1974;14:955-62.
  12. 12. Wong MW, Tsui HF, Yung SH, Chan KM, Cheng JC. Continuous pulse oximeter monitoring for inapparent hypoxemia after long bone fractures. J Trauma. 2004;56:356-62.
  13. 13. Olivera Arencibia Y, Vo M, Kinaga J, Uribe J, Velasquez G, Madruga M, Carlan SJ. Fat Embolism and Nonconvulsive Status Epilepticus. Case Rep Neurol Med. 2018;5057624.
  14. 14. Kao SJ, Yeh DY, Chen HI. Clinical and pathological features of fat embolism with acute respiratory distress syndrome. Clin Sci (Lond). 2007;113:279-85.
  15. 15. Smith AL. What Is the Best E&M of Fat Embolism Syndrome? Hospitalist. 2012;8.
  16. 16. Scotton WJ, Kohler K, Babar J, Russell-Hermanns D, Chilvers ER. Fat embolism syndrome with Purtscher’s retinopathy. Am J Respir Crit Care Med. 2013;187:106.
  17. 17. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;52:732-7.
  18. 18. Ong SC, Balasingam V. Characteristic imaging findings in pulmonary fat embolism syndrome (FES). Case Rep. 2017;bcr-2017.
  19. 19. Dwivedi S, Kimmel LA, Kirk A, Varma D. Radiological features of pulmonary fat embolism in trauma patients: a case series. Emerg Radiol. 2022;29(1):41-7.
  20. 20. Piolanti M, Dalpiaz G, Scaglione M, Coniglio C, Miceli M, Violini S, Trisolini R, Barozzi L. Fat embolism syndrome: lung computed tomography findings in 18 patients. J Comp Assisted Tomography. 2016;40(3):335-42.
  21. 21. Ryu CW, Lee DH, Kim TK, Kim SJ, Kim HS, Lee JH, et al. Cerebral fat embolism: diffusion-weighted magnetic resonance imaging findings. Acta Radiol. 2005;46:528-33.
  22. 22. Webb DP, McKamie WA, Pietsch JB. Resuscitation of fat embolism syndrome with extracorporeal membrane oxygenation. J Extra Corpor Technol. 2004;36:368-70.
  23. 23. Husebye EE, Lyberg T, Røise O. Bone marrow fat in the circulation: clinical entities and pathophysiological mechanisms. Injury. 2006;37(4):S8-18.
  24. 24. Simon AD, Ulmer JL, Strottmann JM. Contrast-enhanced MR imaging of cerebral fat embolism: case report and review of the literature. Am J Neuroradiol. 2003;24(1):97-101.
  25. 25. Prakash S, Sen RK, Tripathy SK, Sen IM, Sharma RR, Sharma S. Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study. Clin Orthop Relat Res. 2013;471:2340-6.
  26. 26. 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. 2009;52:386-93.
  27. 27. 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. Canad J Surg. 2009;52(5):386.
  28. 28. Bone LB, Johnson KD, Weigelt J, Scheinberg R. Early versus delayed stabilization of femoral fractures. A prospective randomized study. J Bone Joint Surg Am. 1989;71:336-40.
  29. 29. Pape HC. Effects of changing strategies of fracture fixation on immunologic changes and systemic complications after multiple trauma: damage control orthopedic surgery. J Orthop Res. 2008;26(11):1478-84.
  30. 30. Habashi NM, Andrews PL, Scalea TM. Therapeutic aspects of fat embolism syndrome. Injury. 2006;37(4):S68-73.
  31. 31. Kellogg RG, Fontes RB, Lopes DK. Massive cerebral involvement in fat embolism syndrome and intracranial pressure management. J Neurosurg. 2013;119:1263-70.
  32. 32. Berlot G, Bussani R, Shafiei V, Zarrillo N. Fulminant Cerebral Fat Embolism: Case Description and Review of the Literature. Case Rep Crit Care. 2018;7813175.