1

C OPYRIGHT Ó 2018 BY T HE J OURNAL OF B ONE AND J OINT S URGERY, I NCORPORATED

Early-Onset Fat Embolism Syndrome

A Case Report
Kevin J. Cronin, MD, Christopher B. Hayes, MD, and Eric S. Moghadamian, MD

Investigation performed at the Department of Orthopaedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky

Abstract
Case: We present the case of a 26-year-old otherwise healthy man with an isolated tibial and fibular shaft fracture who
developed signs of fat embolism syndrome (FES) within 6 hours of injury and prior to any operative treatment.
Conclusion: General orthopaedists and traumatologists should be aware that the onset of FES is not always delayed
for several days, but can develop within 6 hours of injury. After initiation of appropriate management, including res-
piratory support, our patient did well. There was union of the fracture, and he was able to return to work at 3 months
postinjury.

F
at embolism syndrome (FES) was first described in 1861
after Zenker discovered fat globules in the pulmonary
vasculature of a railroad worker who died of a crush
injury. Shortly thereafter, von Bergman described the first
clinical case in a man who sustained a femoral fracture, which
was followed by respiratory distress, coma, and, ultimately,
death1-3. FES has been described in patients with open and
closed fractures, isolated injuries, and polytrauma, and after
operative and nonoperative treatment4,5. The average time from
injury to symptom presentation is 48.5 hours6.
We present the case of a young, otherwise healthy patient
with an open tibial and fibular shaft fracture who developed
FES within 6 hours of injury, an extremely atypical time frame,
which, to our knowledge, has not been described previously.
The patient was informed that data concerning the case
would be submitted for publication, and he provided consent.
Case Report
shaft fracture (OTA/AO classification 42-A3)7 (Fig. 1). The
wounds were irrigated at the bedside, a sterile dressing was
placed, and the fracture was provisionally stabilized with a
long leg plaster splint.
At 6 hours after injury (4 hours after presentation), the
patient began to show signs of altered mental status and res-
piratory distress. He became confused and no longer oriented
to time or place, as well as amnesic to the events prior to the
accident. The heart rate was elevated, and the oxygen saturation
dropped to 78% on room air, requiring 3 L of oxygen via nasal
cannula to maintain an appropriate oxygen saturation. A chest
radiograph showed evidence of noncardiac pulmonary edema
(Fig. 2). No petechial rash was present, and the symptoms were
attributed to the use of narcotics for pain control, which had
been received in the emergency department.
Prior to surgical stabilization, the patient was treated
with supportive oxygen and intravenous fluids. A preoperative
medical and anesthetic workup was completed, and prompt

A n otherwise healthy 26-year-old man presented after sus-

taining an isolated crush injury to the right lower extremity.
He had been working at a factory when a slab of marble granite
fell on the leg, with an estimated extraction time of 1 minute.
On initial presentation, the patient was alert and oriented to
person, place, and time. He provided a full history and was able
to recall all of the details of the accident. The vital signs were
within normal limits. There was a 2.5-cm oblique laceration to
the anterior aspect of the tibia, with no gross contamination or
arterial injury. The neurovascular examination was normal,
and there were no signs of compartment syndrome. Radio-
graphs demonstrated a displaced, transverse tibial and fibular
surgical debridement and stabilization were dictated because
of the grade-II open fracture. The patient was taken to the
operating room within 24 hours of the injury for irrigation and
debridement, and reamed intramedullary nailing was per-
formed. The vital signs remained stable during the operation;
however, he decompensated again immediately postopera-
tively. He became mentally altered, and the oxygen saturation
dropped to 78% on room air. He required 10 L of oxygen to
maintain a saturation of >92%. A bedside echocardiogram
showed strain on the right side of the heart, and a chest radi-
ograph demonstrated worsening bilateral pleural effusions
(Fig. 3). A spiral computed tomography angiography (CTA) of

Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest
forms are provided with the online version of the article (http://links.lww.com/JBJSCC/A699).

JBJS Case Connect 2018;8:e44 d http://dx.doi.org/10.2106/JBJS.CC.17.00175

 2
J BJ S C A S E C O N N E C T O R E A R LY -O N S E T F AT E M B O L I S M S Y N D R O M E
V O LU M E 8 N U M B E R 2 J U N E 27, 2 018
d d

Fig. 1
Anteroposterior (left) and lateral (right) radiographs of the right tibia and fibula demonstrate a comminuted, transverse, displaced fracture of the midshaft of
the tibia and the fibula.

Fig. 2
Anteroposterior radiograph of the chest with diffuse interstitial opacities in the absence of pleural effusions and cardiomegaly.
 3
J BJ S C A S E C O N N E C T O R
V O LU M E 8 N U M B E R 2 J U N E 27, 2 018
d d
Fig. 3
Anteroposterior radiograph of the chest with worsening bilateral interstitial thickening and new hazy opacities with traces of pleural effusions.
the chest and noncontrast magnetic resonance imaging (MRI)
of the head were performed, and the results of both were
consistent with FES (Figs. 4 and 5). A petechial rash was now
visible on the torso, and the diagnosis of FES was made.
The patient improved from a respiratory standpoint
with supportive treatment. However, he remained altered
in orientation to place and time with dysarthria for 5 days
postoperatively. He ultimately returned to the premorbid
baseline pulmonary and neurocognitive status prior to dis-
charge on postoperative day 8. The fracture achieved union,
and the outcome was excellent at 3 months; however, the
immediate postoperative course had been complicated by
prolonged hospitalization and a short-term inpatient rehabil-
itation stay. He had returned to work at 3 months postopera-
tively with no residual deficits, and the last follow-up was at
12 months.
Discussion
E ven with many descriptions in the current literature, there
is no universally accepted definition of FES. Gurd proposed
a system with major and minor criteria in 19708; however,
because of the complexity of the criteria, a simpler defini-
tion of hypoxia, petechial rash, and neurologic impairment
typically is accepted4. Debate mostly centers on the rate,
morbidity, and mortality of this clinical entity. The original
epidemiologic study by Ganong showed a rate of 23% in
patients with isolated fractures of the femur and tibia in a
population of otherwise healthy young skiers, who typically
required prolonged hospitalization1. More recent studies have
E A R LY -O N S E T F AT E M B O L I S M S Y N D R O M E
shown the rate to be lower, with most authors in agreement
that the rate is between 0.9% and 11% for isolated femoral
and tibial fractures9,10. In Gurd’s original 1970 paper, he es-
timated that 67% of trauma patients have some degree of fat
embolism without any clinical symptoms8, and more recent
work has raised that estimate to 100%. The difference in rate
has been attributed to varying severity, concomitant chest and
head injuries in patients with polytrauma, and the lack of a
verifiable diagnostic test.
The temporal relationship of symptoms to injury also
remains poorly defined. Animal studies in dogs have shown
pulmonary hypertension to occur within hours of injury1;
however, the average time to symptom onset has been shown
to be 48.5 hours, with most patients showing signs and symp-
toms within 72 hours6. Our patient developed symptoms within
6 hours of the injury and prior to any operative intervention.
However, the diagnosis was not made until he experienced
postoperative pulmonary and neurologic deterioration, al-
though, in retrospect, FES was present preoperatively at 6
hours postinjury.
Certain patients with various mechanisms of injury are at
higher risk of FES than others. Younger patients with multiple
closed long bone fractures after a crush injury and delayed
stabilization are the group that is at highest risk for developing
FES11. It is hypothesized that crushing mechanisms increase the
soft-tissue and osseous damage, resulting in more fat globules
being released into the bloodstream12. Our patient was at risk
for the development of FES given his young age, the long bone
fracture, and the crushing mechanism.
 4
J BJ S C A S E C O N N E C T O R
V O LU M E 8 N U M B E R 2 J U N E 27, 2 018
d d
Fig. 4
CTA of the chest demonstrating diffuse interlobular septal thickening with a
superimposed ground-glass abnormality, as well as numerous discrete
small nodules that are consistent with FES.
FES often is considered a subset of acute respiratory
distress syndrome (ARDS). A definitive cause has not yet been
established, and 2 leading theories have been proposed: the
mechanical and biochemical theories. The mechanical theory
is supported by the work of Aoki et al.13 and Pell et al.14,
proposing that fat cells from bone marrow are seeded into the
circulatory system at the time of injury, causing direct injury
to the lungs and brain. The biochemical theory states that
when these same fat globules enter the respiratory system,
Fig. 5
MRI of the head without contrast demonstrating numerous tiny foci of acute infarction throughout the brain, suggestive of a central embolic
process.
E A R LY -O N S E T F AT E M B O L I S M S Y N D R O M E
they are broken down into free fatty acids, leading to a
microvascular inflammatory response and acute lung injury15.
This interferes with the oxygenation of the blood and leads to
hypoxemia. Mental status changes result from inflammation
from the deposition of these free fatty acids in neural tissue.
This has most recently been supported by Prakash et al., who
showed a higher level of proinflammatory cytokines, specif-
ically interleukin-6, in patients with polytrauma and FES at
12 hours after injury compared with those without FES16.
Our case highlights the multifactorial nature of FES given
the early-onset presentation, which likely occurred prior to
the effect of the proinflammatory cytokine cascade, with
sustained and worsening symptomatology occurring later in
the clinical course. Thus, the underlying mechanism of FES
is likely a combination of both the mechanical and bio-
chemical theories.
Many treatment modalities have been utilized, including
heparin and corticosteroid therapy, with little support in the lit-
erature17. Current treatment includes pulmonary support, man-
agement of circulatory shock, and early long-bone-fracture
fixation, as indicated. Talbot and Schemitsch were the first to
theorize that early fracture stabilization could prevent FES18.
Later, Pinney et al.19 showed that early rather than late in-
tramedullary nailing of femoral fractures decreased the rate
of FES. Even with timely stabilization, our patient man-
ifested early symptoms and, despite operative stabilization,
experienced continued clinical progression. Some may suggest
that these worsening clinical symptoms may, in part, be related
to treatment with a reamed intramedullary nail. However, an
increase in FES has not been demonstrated with reamed or
unreamed nailing versus open reduction and internal fixation.
Multiple recent studies have shown no increased risk of devel-
oping or worsening FES with reamed intramedullary nailing12,20,21.
While Aoki et al. and Pell et al. showed the presence of fat emboli
in the cardiac chambers during reamed intramedullary nailing of
 5
J BJ S C A S E C O N N E C T O R
V O LU M E 8 N U M B E R 2 J U N E 27, 2 018
d d
long bone fractures through the use of transesophageal ech-
ocardiography, no relation was elicited between the presence
of emboli and FES13,14. Reamed intramedullary nailing was
chosen for our patient given the lack of increased risk of FES
and the decreased rate of nonunion12,20-22. The postoperative
respiratory and mental deterioration in our patient suggests
that a delay in definitive stabilization might have been appro-
priate. However, the response to pulmonary support and the
excellent recovery to full function support early definitive
fixation.
FES is a well-known and often devastating complica-
tion of long bone fractures in patients with polytrauma. It
is important for all clinicians to be aware of the triad of
hypoxia, petechial rash, and neurologic derangement while
treating this subset of patients. The clinical outcomes are
wide, ranging from full function without sequelae to death,
with an overall mortality rate of up to 10%17. To our knowledge,
this case report is the first published case of FES that
occurred within 6 hours of an open isolated long bone
References
1. Ganong RB. Fat emboli syndrome in isolated fractures of the tibia and femur. Clin
Orthop Relat Res. 1993 Jun;(291):208-14.
2. Zenker FA. Beitrage zur anatomie und physiologoie de lung. Dresden:
J. Braunsdor; 1861. p 20.
3. Randelli F, Capitani P, Pace F, Favilla S, Galante C, Randelli P. Bilateral femoral
shaft fractures complicated by fat and pulmonary embolism: a case report. Injury.
2015 Dec;46(Suppl 7):S28-30.
4. Sara S, Kenyhertz G, Herbert T, Lundeen GA. Fat emboli syndrome in a non-
displaced tibia fracture. J Orthop Trauma. 2011 Mar;25(3):e27-9.
5. Aparicio G, Soler I, López-Durán L. Fat embolism syndrome after nailing an isolated
open tibial fracture in a stable patient: a case report. BMC Res Notes. 2014 Apr 14;7:237.
6. Tsai IT, Hsu CJ, Chen YH, Fong YC, Hsu HC, Tsai CH. Fat embolism syndrome in
long bone fracture—clinical experience in a tertiary referral center in Taiwan. J Chin
Med Assoc. 2010 Aug;73(8):407-10.
7. Marsh JL, Slongo TF, Agel J, Broderick JS, Creevey W, DeCoster TA, Prokuski L,
Sirkin MS, Ziran B, Henley B, Audigé L. Fracture and dislocation classification
compendium – 2007: Orthopaedic Trauma Association Classification, Database and
Outcomes Committee. J Orthop Trauma. 2007 Nov-Dec;21(10)(Suppl):S1-133.
8. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970 Nov;
52(4):732-7.
9. Fabian TC, Hoots AV, Stanford DS, Patterson CR, Mangiante EC. Fat embolism
syndrome: prospective evaluation in 92 fracture patients. Crit Care Med. 1990 Jan;
18(1):42-6.
10. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-
year review. Arch Surg. 1997 Apr;132(4):435-9.
11. Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammersch-
midt DE, Jacob HS. Fat embolism prophylaxis with corticosteroids. A prospective
study in high-risk patients. Ann Intern Med. 1983 Oct;99(4):438-43.
12. Högel F, Gerlach UV, Südkamp NP, Müller CA. Pulmonary fat embolism after
reamed and unreamed nailing of femoral fractures. Injury. 2010 Dec;41(12):1317-
22. Epub 2010 Sep 17.
E A R LY -O N S E T F AT E M B O L I S M S Y N D R O M E
fracture in a young, healthy man with no head or chest trauma.
This case of FES, which presented as early as 6 hours after
injury and prior to operative intervention, brings awareness of
the possibility of early-onset FES. The temporal relationship
between injury and symptoms should not be used as a diag-
nostic criterion. Recognition and treatment are important to obtain
optimal short and long-term outcomes in patients with FES. n
Kevin J. Cronin, MD1
Christopher B. Hayes, MD1
Eric S. Moghadamian, MD1
1Department of Orthopaedic Surgery and Sports Medicine, University of
Kentucky, Lexington, Kentucky
E-mail address for K.J. Cronin: Kevin.Cronin@uky.edu
ORCID iD for K.J. Cronin: 0000-0001-8337-1699
13. 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 Jan;113(1):178-81.
14. 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 Nov;
75(6):921-5.
15. Kosova E, Bergmark B, Piazza G. Fat embolism syndrome. Circulation. 2015 Jan
20;131(3):317-20.
16. 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 Jul;471(7):2340-6. Epub 2013 Feb 20.
17. Habashi NM, Andrews PL, Scalea TM. Therapeutic aspects of fat embolism
syndrome. Injury. 2006 Oct;37(Suppl 4):S68-73.
18. Talbot M, Schemitsch EH. Fat embolism syndrome: history, definition, epide-
miology. Injury. 2006 Oct;37(Suppl 4):S3-7.
19. Pinney SJ, Keating JF, Meek RN. Fat embolism syndrome in isolated femoral
fractures: does timing of nailing influence incidence? Injury. 1998 Mar;29(2):
131-3.
20. Högel F, Kamer L, Schlegel U, Rahn B, Südkamp NP, Müller CA. Fat extrava-
sation due to unreamed and experimentally reamed intramedullary nailing of the
sheep femur. Injury. 2009 Jul;40(7):718-21. Epub 2009 Mar 28.
21. Klein C, Sprecher C, Rahn BA, Green J, Müller CA. Unreamed or RIA reamed
nailing: an experimental sheep study using comparative histological assessment
of affected bone tissue in an acute fracture model. Injury. 2010 Nov;41(Suppl 2):
S32-7.
22. Bhandari M, Guyatt G, Tornetta P 3rd, Schemitsch EH, Swiontkowski M,
Sanders D, Walter SD; Study to Prospectively Evaluate Reamed Intramedullary Nails
in Patients with Tibial Fractures Investigators. Randomized trial of reamed and un-
reamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg Am. 2008
Dec;90(12):2567-78.