Fat Embolism Syndrome

PAUL D. STEIN, MD; ABDO Y. YAEKOUB, MD; FADI MATTA, MD;MICHAEL KLEEREKOPER, MD

ABSTRACT: Objectives: To assess the incidence and riskfactors for fat embolism syndrome. Materials and Meth-ods: Data from the National Hospital Discharge Survey(NHDS) were analyzed using International Classificationof Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Results: From 1979 through 2005 among928,324,000 patients discharged from short-stay hospi-tals in the United States, 41,000 (0.004%) had fat em-bolism syndrome. Among 21,538,000 patients with anisolated fracture of the femur (any site), tibia, fibula,pelvis, ribs, humerus, radius, or ulna, 25,000 (0.12%)developed fat embolism syndrome. Patients with multi-ple fractures of the femur (excluding neck) more oftenhad fat embolism syndrome than those with isolatedfractures (1.29% versus 0.54%). The incidence of fatembolism syndrome was lower with isolated fractures of

the tibia or fibula (0.30%) and even lower with isolatedfractures of the neck of the femur (0.06%). The inci-dence of fat embolism was too low to calculate withisolated fractures of the pelvis, ribs, humerus, radius, orulna. Nonorthopedic conditions rarely, if ever, wereaccompanied by fat embolism syndrome. The fat embo-lism syndrome was more frequent in men (relative risk5.71). Children, aged 0 to 9 years rarely had fat embo-lism syndrome. The fat embolism syndrome most com-monly affected patients aged 10 to 39 years. Conclu-sions: The incidence of the fat embolism syndromedepends on the bone involved, whether fractures areisolated or multiple, the age of the patient and thegender. It rarely occurs as a result of medical conditions.KEY INDEXING TERMS: Fat embolism syndrome; Frac-tures. [Am J Med Sci 2008;336(6):472–477.]

Fat embolism syndrome is a serious manifesta-tion of fat embolism that involves progressive

respiratory insufficiency, deteriorating mental sta-tus, and petechial rash1 usually occurring within 72hours of injury.2 Mortality from fat embolism syn-drome in case series of 7 to 100 patients ranged from6% to 29%,3–11 and a series of 208 patients with fatembolism syndrome collected from 1963 to 1983showed a mortality of 54%.12 Early fixation andmodern critical care should help minimize the im-pact of fat embolism.13 The reported incidence of fatembolism syndrome in patients with fracturesranges widely, from 0%6,14 to 35%.6 In the largerreported case series, however, that evaluated some-what over 3000 patients to nearly 17,000 patientswith fractures or patients hospitalized with injuries,the incidence of fat embolism syndrome ranged from0.3% to 1.3%.4,5,12,15,16 In view of the importance offat embolism syndrome, and sparse data on theincidence and categories of patients at risk, we an-

alyzed data from the National Hospital DischargeSurvey (NHDS).

Materials and Methods

Data SourcesThe number of patients discharged from short-stay nonfederal

hospitals throughout the United States with a diagnostic code forfat embolism from 1979 through 2005 was obtained from theNHDS.17 Among these patients, the number with fractures atvarious sites and illnesses reported to be associated with fatembolism syndrome were determined. The NHDS consists of dataobtained annually from approximately 270,000 sampled inpa-tient records from about 500 non-Federal short-stay hospitals(average length of stay �30 days) in 50 states and the District ofColumbia.17

Identification of Fat Embolism SyndromeThe International Classification of Diseases, Ninth Revision,

Clinical Modification (ICD-9-CM) code used for fat embolism was958.1.

Identification of FracturesThe ICD-9-CM codes used for fractures of the pelvis were 808,

humerus 812, radius or ulna 813, femoral neck 820, femur otherand unspecified sites 821, and tibia and fibula 823.

Identification of ProceduresProcedures that we identified with ICD-9-CM codes were bone

graft 78.0, limb shortening 78.2, limb lengthening 78.3, internalfixation 78.5, joint replacement of lower extremity 81.5, arthro-plasty and repair of shoulder and elbow 81.8.

Identification of IllnessesIllnesses identified by ICD-9-CM codes were decompression

sickness 993.3, burns, third degree 941.3, bone marrow trans-

From the Department of Research, St. Joseph Mercy OaklandHospital (PDS, AYY, FM), Pontiac, Michigan; Wayne State Univer-sity School of Medicine (PDS), Detroit, Michigan; and the Depart-ment of Medicine, St. Joseph Mercy Hospital (MK), Ann Arbor,Michigan.

Submitted February 7, 2008; accepted in revised form March 7,2008.

Correspondence: Paul D. Stein, MD, Saint Joseph Mercy Oak-land, 44405 Woodward Avenue, Pontiac, MI 48341-5023 (E-mail:steinp@trinity-health.org).

472 December 2008 Volume 336 Number 6

plant 996.85, V42.4, V42.8, bone marrow transplant donor V59.2,V59.3, crush 929.9, pancreatitis 577.0, diabetes mellitus 250.0,panniculitis 729.30, fatty liver 571.0, 571.8, and sickle cell ane-mia 282.6.

Statistical Analysis and Methodological ConsiderationsRelative risk and 95% confidence intervals (CI) were calculated

using calculator for confidence intervals of relative risk (www.sign.ac.uk/methodology/risk.xls).

Results

From 1979 through 2005 among 928,324,000 pa-tients discharged from short-stay hospitals, 41,000(0.004%) had fat embolism syndrome. The incidenceof fat embolism remained relatively unchanged overthe interval of study (Table 1). Among 23,829,000patients with isolated or multiple fractures involv-ing the femur (any site), tibia, fibula, pelvis, ribs,humerus, radius, or ulna, 41,000 (0.17%) developedfat embolism syndrome. The fracture site most fre-quently responsible for fat embolism was the femur(Figure 1). The incidence of fat embolism was higherin patients with multiple fractures of these sites[16,000 of 2,291,000 (0.70%)] than in patients withisolated fractures of these sites [25,000 of 21,538,000(0.12%) (P � 0.0001)].

Among 388,000 patients with multiple fracturesthat included the femur (excluding neck), 1.29% hadfat embolism syndrome (Table 2). Among 1,643,000

patients with isolated fractures of the femur (exclud-ing neck), fewer (0.54%) developed fat embolismsyndrome (P � 0.0001) (Table 2). The incidence offat embolism syndrome was lower in patients withisolated fractures of the tibia or fibula (0.30%) andeven lower in patients with isolated fractures of theneck of the femur (0.06%) (Table 2). The incidence offat embolism was too low to calculate with isolatedfractures of the pelvis, ribs, humerus, radius, orulna. Even taken together, patients with any ofthese isolated fractures showed an incidence of fatembolism too low to calculate accurately (Table 2).

The incidence of fat embolism syndrome in pa-tients who had internal fixation, with or withoutopen fracture reduction was 0.15% of 11,862,000(Table 2). The incidence of fat embolism syndrome inpatients with joint replacement of the lower extrem-ity, arthroplasty and repair of shoulder or elbow,bone graft, limb shortening, limb lengthening, os-teotomy, and spinal fusion were too low to calculateaccurately.

Nonorthopedic conditions including decompres-sion sickness, third degree burns, bone marrowtransplantation, crushing injury (excluding frac-ture), pancreatitis, diabetes mellitus, panniculitis,fatty liver, and sickle cell anemia were either notaccompanied by fat embolism syndrome or onlyrarely, and the incidences were too low to calculateaccurately.

The fat embolism syndrome was more frequent inmen (relative risk 5.71) (Table 3). A higher propor-tion of men had fractures of the femur (excludingneck), tibia or fibula than women (25% versus 14%),and fewer men had isolated fractures of the neck ofthe femur (24%) than women (45%). Fractures of thepelvis, ribs, humerus radius, or ulna occurred in51% of men and 41% of women.

Among 1,178,000 patients aged 0 to 9 years whohad isolated fractures of the femur (any site), tibia,

Table 1. Incidence of Fat Embolism Syndrome According toYear

Years(5-year Interval)

Incidence(Fat Embolism Syndrome/5 yrs)

1981–1985 80001986–1990 10,0001991–1995 70001996–2000 �50002000–2005 9000

34

25

17

24

0

10

20

30

40

Femur Other thanNeck

Tibia or Fibula Femur Neck Pelvis/Humerus/Ribs/Radius or

Ulna

Fat E

mbo

lism

Syn

(%)

Isolated or Multiple Fractures

Figure 1. Percentage of hospitalized patients withthe fat embolism syndrome (syn) who had isolatedor multiple fractures of the femur (other thanneck), tibia or fibula, neck of the femur, or pelvis,humerus, ribs, or ulna.

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fibula, pelvis, ribs, humerus, radius, or ulna, theincidence of fat embolism syndrome was too low tocalculate accurately (Table 3). The fat embolismsyndrome in patients aged 10 to 19 years and 20 to39 years was more frequent (0.37% in both agegroups) than in patients aged 40 years and older(incidence 0.05%). Comparing patients aged 20 to 39years with patients �40 years the relative risk was7.34 (Table 3).

Discussion

The incidence of fat embolism syndrome that weobserved among 3,979,000 patients with isolatedfractures of the femur (excluding neck), tibia orfibula, 0.40%, was in the range observed by others incase series of at least 3000 patients, 0.3% to1.2%4,5,12,15,16 (Table 4). The reported incidences offat embolism syndrome among patients with singleor multiple fractures or various injuries ranges from0 to 17%.3–6,10,12,14–16,18–22 (Table 4). The relativerisk of fat embolism syndrome that we observed inpatients with multiple fractures involving the femur(excluding neck), compared with isolated fracturesof the femur (excluding neck), was 2.35. Similarly,

published data show a relative risk of fat embo-lism syndrome in patients with multiple fracturescompared with isolated fractures of 2.29 (Table4).2,6,10,18,23–25 The higher risk of patients with mul-tiple fractures has been described.5,7,8,26,27

The incidence of fat embolism syndrome that weobserved was much higher in patients with longbone fractures of the lower extremity than that ofthe arm, as has been observed previously.4 The in-cidence of fat embolism syndrome that we observedwas also 7.6 times higher in patients with isolatedfractures of the femur (excluding neck) than in pa-tients with isolated fractures of the neck of thefemur. The neck of the femur is characterized by redbone marrow in adults, rather than yellow bonemarrow.28

We observed a higher incidence of fat embolismsyndrome in men than in women (relative risk of5.7). Others, among 92 patients with fractures, alsoshowed a higher relative risk for fat embolism syn-drome in men (relative risk 3.6).3 In our patients, ahigher proportion of men than women had fracturesof the femur (excluding neck), tibia, or fibula. Fewermen had fractures of the neck of the femur. Thehigher incidence in men has been suggested to relateto men being more subjected to trauma.29 The de-gree of trauma and extent of associated soft-tissuedamage is likely to be less in women with fracturesthan in men because fracture of the neck of femurmay occur with minimal trauma because of osteopo-rosis.30 There is a rapid and diffuse bone loss inperimenopausal women31 in addition to the univer-sal age-related bone loss that occurs in both men andwomen.32

Children develop fat embolism syndrome almost100 times less frequently than adults with compa-rable injuries.26 Among 1,178,000 children aged 0 to9 years with isolated fractures of the femur (anysite), tibia, fibula, pelvis, ribs, humerus, radius, orulna, we found virtually no cases of fat embolismsyndrome. It has been suggested that the low inci-dence of fat embolism in children is due to the factthat up to 14 years, the fat content of the bone

Table 2. Incidence of Fat Embolism Syndrome According to Location of Fracture or Procedure

Multiple or Isolated FracturesFat Emb/No. Fx (%)

Multiple FracturesFat Emb/No. Fx (%)

Isolated FracturesFat Emb/No. FX (%)

Relative Risk(95% CI)

Femur (excluding neck) 14,000/2,031,000 (0.68) 5,000/388,000 (1.29) 9,000/1,643,000 (0.54) 2.35 (2.27–2.43)a

Femur, neck 7,000/8,387,000 (0.09) b/7,551,000 5,000/7,836,000 (0.06) —Tibia or fibula 10,000/2,747,000 (0.40) b/411,000 7,000/2,336,000 (0.30) —Pelvis, ribs, humerus,

radius, ulna10,000/10,664,000 (0.09) b/942,000 b/9,722,000 —

Internal fixation (with orwithout open fracture reduction)

18,000/11,862,000 (0.15) b b —

a Multiple fractures involving the femur (excluding neck), compared with isolated fractures of the femur (excluding neck).b Too few fat emboli to accurately calculate incidence.Emb indicates embolism; Fx, fracture.

Table 3. Incidence of Fat Embolism Syndrome According toGender and Age Among Patients with Isolated Fractures of

Femur (any site), Tibia, Fibula, Pelvis, Ribs, Humerus, Radius,or Ulna

Fat Emb/No. Fx (%) Relative Risk (95% CI)

Men 20,000/8,872,000 (0.23) 5.71 (5.54–5.89)a

Women 5,000/12,665,000 (0.04)Age (years)

0–9 b/1,178,00010–19 6,000/1,621,000 (0.37)20–39 11,000/2,947,000 (0.37) 7.34 (7.13–7.55)c

�40 8,000/15,729,000 (0.05)

a Comparing men with women.b Too few fat emboli to accurately calculate incidence.c Comparing patients aged 20 to 39 years with patients �40 years.Emb indicates embolism; Fx, fracture.

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marrow is low, with a greater proportion of highermelting fats, palmitin and stearin, and less of thefluid fat, olein.29 Palmitin and stearin (in the bonemarrow of children) are not as likely to produceemboli as olein, found in the marrow of adults.2 Anorderly progression of red to yellow marrow conver-sion in the femur was appreciated first in the diaph-ysis (ages 1–10 years) and then in the distal metaph-ysis (ages 10–20 years), with an adult pattern seenby age 24 years.33

Among patients aged 10 to 19 and aged 20 to 39years, the relative risk compared with patients aged40 years or older was 7.34. Others, among 321 pa-tients with long bone injury, found a higher relativerisk for fat embolism syndrome among patients aged11 to 40 years than age 41 years and older (relativerisk 13.15).34 In another investigation, no fat embo-lism syndrome was observed among 105 patientsaged 35 years or older, but 6.5% developed fat em-bolism syndrome among 169 patients aged 13 to 34years.23 They speculated that patients under age 35years (who are prodominantly male) in general sus-tain injuries as a consequence of high-energy trau-

ma.23 Bone mineral content and bone mineral den-sity decrease with age beginning at around age 40years35 or perhaps 30 to 35 years.36 Minimal traumafractures may result in patients with decreased bonedensity, which particularly occurs in women aftermenopause.32,37 Because fractures of the neck of thefemur often are minimal trauma fractures and areassociated with a low risk of fat embolism syndrome,it may be that minimal trauma fractures whichoccur predominantly in sites rich in cancellous bone(ie, richer in red marrow), result in a low risk of fatembolism syndrome.

Several clinical settings for fat embolism syn-drome have been named according to the broadcategories of trauma, surgery, and nontrauma.38

The medical conditions and nonorthopedic proce-dures that we evaluated were only rarely accompa-nied by fat embolism syndrome, or in some in-stances, or not at all. Occasional cases of fatembolism syndrome occur, however, in many clinicalsettings38 including diabetes mellitus,39 pancreati-tis,40 burns,2 bone marrow transplant,41 sickle celldisease,42 osteomyelitis,43 fatty liver,44 and soft tis-

Table 4. Incidence of Fat Embolism

Fat Embolism Syndrome, n/N (%) Characteristics of Population at RiskFirst Author, Year

(Reference)

Incidence of fat embolism in patientswith isolated fractures

1/70 (1.4) Isolated femur (excluding neck) Chow, 198018

11/274 (4.0) Isolated femur (excluding neck) Pinney, 199823

6/175 (3.5) Isolated femur (excluding neck) Ten Duis, 198824

7/64 (10.9) Isolated fracture of femur (excluding neck), tibia,or fibula

Myers, 197710

0/60 (0.0) Isolated fracture of femur (excluding neck), or tibia Chan, 19846

Incidence of fat embolism in patientswith multiple fractures or injuries

6/25 (24.0) Multiple fractures of femur and other sites Chow, 198018

7/20 (35.0) Multiples fractures involving femur or tibia andpelvis or other sites

Chan, 19846

10/36 (27.8) Multiple fractures of femur (excluding neck), tibia,or fibula and other sites

Myers, 197710

3/211 (1.4) Long bone fractures and multiple injuries Riska, 198225

Incidence of fat embolism withmultiple or single fractures

38/4,197 (0.9) Fractures Magerl, 196615

47/3,650 (1.3) Fractures Pelzl, 196916

208/16,706 (1.2) Hospitalized with injuries Kroupa, 198812

7/95 (7.4) Fractures of femur (excluding neck) Chow, 198018

5/43 (11.6) Fractures of femur (excluding neck) Allardyce, 197419

0/50 (0.0) Fractures of extremities McCarthy, 197314

7/80 (8.8) Fractures of femur (excluding neck), or tibia, andpelvis or multiple other sites

Chan, 19846

41/812 (5.0) Lower extremity and pelvic fractures Boricov, 200620

27/3,026 (0.9) Fracture of femur, tibia, fibula, or humerus Bulger, 19974

17/6,564 (0.3) Fracture of femur (excluding neck), tibial shaft, orpelvis

Robert, 19935

17/100 (17.0) Fracture of femur (excluding neck), tibial, or fibula Myers, 197710

10/92 (10.9) Fracture of femur, tibia or pelvis Fabian, 19903

11/82 (13.4) Fracture of long bones Kallenbach, 198721

9/62 (14.5) Fracture of femur, tibia, or fibula Schoenfeld, 198322

n indicates number with fat embolism syndrome; N, number at risk.

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475THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

sue injury.45 Regarding orthopedic procedures, wefound an incidence of fat embolism syndrome inpatients who had internal fixation, with or withoutopen fracture reduction of 0.15%. The incidence offat embolism syndrome in patients that we identi-fied with other orthopedic procedures was too low tocalculate accurately. Delayed stabilization is associ-ated with a higher incidence of fat embolism syn-drome, compared with prompt stabilization.5,23

Closed fractures are associated with a higher inci-dence of fat embolism than open fractures.4

The incidence of fat embolism syndrome is proba-bly underestimated.18 It is often not possible tomake the diagnosis of fat embolism syndrome.4 Ma-jor clinical features are (1) respiratory symptomsplus bilateral signs on chest examination with pos-itive radiographic changes, (2) petechial rash, and(3) cerebral signs unrelated to head injury or othercondition.1 Respiratory findings were later de-scribed as “respiratory insufficiency”46 or hypoxia(PaO2 �60 mm Hg).4 Minor features are fever,tachycardia, retinal changes (fat or petechiae), renalchanges (anuria, oliguria, fat globules), sudden dropin hemoglobin, sudden thrombocytopenia, higherythrocyte sedimentation rate, and fat globules inthe sputum.1 Jaundice was subsequently added tothe minor features, and circulating fat globules wereidentified as a laboratory feature.46 Clinical diagno-sis is the key, because laboratory and roentgeno-graphic findings are nonspecific.38

Strengths of this investigation are the huge pa-tient sample, the diversity of the population in termsof age, race, gender, and geographic region (all 50states and the district of Columbia), the extensiveduration of observation (27 years), and the meticu-lous and statistically robust methods of sampling.17

Limitations include an inability to determine thebasis of the diagnosis of fat embolism syndrome andwhether some patients were diagnosed with fat em-bolism but did not have the findings of the clinicalsyndrome. Also we do not know the severity of thefractures, only the location of isolated fractures.

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