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FECHA DE ENTREGA: 11 DE FEBRERO DEL 2022

 Liposuction-Induced Fat Embolism Syndrome
A Brief Review and Postmortem Diagnostic Approach
Colby A. Cantu, MD; Elizabeth N. Pavlisko, MD
 Lipoplasty, or liposuction, the surgical process of
removing excess fat, is an elective procedure with rising
frequency in the United States. Fat embolism syndrome is a
clinical diagnosis and is defined as fat in the circulation
with an identifiable clinical pattern of signs and symptoms
(eg, hypoxemia, respiratory insufficiency, neurologic im-
pairment, and petechial rash) that occur in the appropriate
clinical context. Fat embolism syndrome following lipo-
suction is a life-threatening complication, although its
incidence is low. Currently, there is no specific therapy for
fat embolism syndrome, so prevention, early detection,
and supportive therapy are critical. Many cases of fat
embolism syndrome are undiagnosed or misdiagnosed;
however, postmortem examination can provide the means
for appropriate diagnosis. Therefore, a pathologist must
keep a keen eye, as microscopic fat emboli are difficult to
appreciate with routine tissue processing and staining.
(Arch Pathol Lab Med. 2018;142:871–875; doi: 10.5858/
arpa.2017-0117-RS)
F at emboli are generated when fat globules enter the
bloodstream from tissue (usually marrow or adipose)
disrupted by trauma or, alternatively, via production of toxic
intermediaries of plasma-derived fat (eg, chylomicrons). A
significant burden of fat emboli may cause specific clinical
manifestations, creating the phenomenon termed fat
embolism syndrome (FES). Despite its having been initially
described in 1861, there remains no diagnostic test that is
sufficiently sensitive or specific for confirming or excluding
FES.1
Fat embolism syndrome is most commonly associated
with long bone and pelvic fractures (bone marrow has high
fat content), but it can also arise from soft tissue trauma
without fracture and from a variety of other nontraumatic
and nonorthopedic traumatic causes, including, but not
limited to, pancreatitis, sickle or thalassemia-related hemo-
globinopathies, alcoholic (fatty) liver disease, renal angio-
myolipoma invasion of the inferior vena cava, bone tumor
Accepted for publication June 7, 2017.
From the Department of Pathology, Duke University Health
System, Durham, North Carolina.
The authors have no relevant financial interest in the products or
companies described in this article.
Corresponding author: Colby A. Cantu, MD, Department of
Pathology, Duke University Health System, Box 3712, Durham,
NC 27710 (email: colby.cantu@gmail.com).
Arch Pathol Lab Med—Vol 142, July 2018
lysis, steroid therapy, and notably, liposuction.2 The first
case of liposuction-induced FES was reported by Christman3
in 1986. The number of liposuction procedures per year
continues to steadily rise in the United States. It was the
most common cosmetic surgical procedure in the United
States in 2015 (305 856 procedures), and the number of
procedures has nearly doubled since 1997 (176 863 proce-
dures), when plastic surgery statistics started being record-
ed. Moreover, 53 554 more procedures occurred in 2015
compared with 2014.4 With rising incidence and a lack of
diagnostic testing, antemortem and postmortem suspicion
should be raised for FES in the setting of recent liposuction.
To date, only 17 cases of liposuction-induced FES with or
without fat grafting have been reported in the literature.3,5–20
PATHOGENESIS
The pathogenesis of FES is unknown. During liposuction
and fat grafting, there is rupture of small blood vessels and
damage to adipocytes, producing lipid microfragments that
reach the venous circulation and consequently cause lung
injury.16,21 Fat emboli can also reach the systemic circulation,
affecting other organs, because of the patency of the
foramen ovale in the interatrial septum, the existence of
pulmonary arteriovenous microfistulas, and the deformation
of the fat microglobules that cross the pulmonary capillar-
ies.22,23 Liposuction-induced FES typically occurs 12 to 72
hours after surgery. In theory, 3 major models have been
proposed to explain the pathogenesis of FES. These theories
exist to help explain the timing and etiology of the embolic
events.
The first theory is the mechanical theory. This theory
postulates that fat droplets are released by disruption of fat
cells in fractured bone or in adipose tissue. These fat
droplets enter the torn veins near the site of injury, and are
then transported to the pulmonary vascular bed, where
large fat globules result in mechanical obstruction and are
trapped as emboli in lung capillaries. The smaller droplets
(7–10 lm) may pass through the lung and reach systemic
circulation, causing embolization to the brain, kidney, skin,
or retina. Large fat droplets may also enter systemic
circulation through preexisting pulmonary precapillary
shunts and pathologic venous-arterial communication such
as patent foramen ovale.24 This theory is corroborated by
studies involving intraoperative transesophageal echocardi-
ography in various types of orthopedic surgeries in which
hypoechogenic intracardiac material is seen passing through
the right heart during the introduction of intramedullary
Liposuction-Induced Fat Embolism Syndrome—Cantu & Pavlisko 871
prosthesis.23 However, this theory fails to explain cases with
delayed symptom onset (.72 hours) after liposuction.
The second theory is the biochemical theory, which helps
explain nontraumatic and delayed fat embolic events. The
biochemical theory proposes that the clinical manifestations
of FES are attributable to a proinflammatory setting. After
reaching the pulmonary capillaries, fat globules are hydro-
lyzed by lipase produced by pneumocytes, producing high
concentrations of glycerol and free fatty acids, which are
toxic to alveoli and endothelial cells. At the onset of the local
injury, vasoactive amines and prostaglandins are released. In
addition, there is neutrophil recruitment, leading to
hemorrhage, as well as interstitial and alveolar edema.
Histopathologically, there is edema, transudate, and subse-
quent alveolar exudate, followed by type II pneumocyte
apoptosis and formation of hyaline membranes. This
hypothesis addresses delayed symptom onset following
liposuction, because agglutination and degradation of the fat
emboli, which are time-consuming biochemical processes,
would be necessary to trigger the local inflammatory
process.12,16,22,23 Further support of the biochemical theory
is endorsed in nontraumatic settings, such as pancreatitis.
Serum from acutely ill patients demonstrates the capacity to
agglutinate chylomicrons, low-density lipoproteins, and
liposomes of nutritional fat emulsions. C-reactive protein
is elevated in these patients, and studies have demonstrated
its ability to induce calcium-dependent lipid agglutination.25
Therefore, C-reactive protein likely participates in this
proposed delayed pathogenesis of nontraumatic FES.24
The third theory, which is the most recent and appears
least supported, is the coagulation theory. This theory
articulates how tissue thromboplastin and marrow elements
are released following long bone fractures, thus activating
the complement system and extrinsic coagulation cascade.
As a result, these events lead to intravascular coagulation via
fibrin and fibrin degradation products. These products
combine with leukocytes, fat globules, and platelets to
increase pulmonary vascular permeability in 2 ways: direct
actions on endothelial cells, and via release of vasoactive
substances.24 The coagulation theory fails to explain the
etiology of nontraumatic FES.
These 3 theories are not mutually exclusive, and have all
been described after major traumas involving long bone
fracture, as well as after intramedullary orthopedic proce-
dures.22 It is likely they all play a contributory role in the
pathogenesis of FES as it relates to the etiology (traumatic
versus nontraumatic) and time course.
CLINICAL FEATURES
The clinical manifestations of and diagnostic criteria for
FES were first described by Gurd in 1970,33 and later refined
by Gurd and Wilson26 in 1974. The refined criteria are
currently the gold standard for FES diagnosis, although
alternative diagnostic criteria have been proposed.27 The
refined criteria state that at least 2 major signs/symptoms, or
1 major and 4 minor signs/symptoms, must be present to
diagnosis the syndrome (Table). Fat embolism syndrome is
most common after long bone or pelvic fractures, and less
common among all other etiologies. Although FES typically
manifests 24 to 72 hours after initial insult, it may rarely
occur as early as 12 hours or as late as 2 weeks after the
inciting event.28 Many affected patients fail to develop the
classic triad. A study by Bulger et al29 identified 27 patients
with FES, of whom 26 (96%) exhibited respiratory mani-
872 Arch Pathol Lab Med—Vol 142, July 2018
Gurd and Wilson’s Criteria for the Diagnosis of Fat
Embolism Syndromea
Major criteria
Respiratory insufficiency
Cerebral involvement
Petechial rash
Minor criteria
Fever (typically .38.58C)
Tachycardia (.110 beats/min)
Jaundice
Retinal changes
Renal changes
Anemia
Thrombocytopenia
Elevated erythrocyte sedimentation rate
Fat macroglobulinemia
a
Data derived from Gurd and Wilson.26
festations, but only 16 (59%) and 9 (33%), respectively,
demonstrated neurologic abnormalities and a petechial skin
rash.
Respiratory changes are usually the first clinical manifes-
tation, and most frequently includes dyspnea, tachypnea,
and hypoxemia. Respiratory abnormalities tend to vary in
severity, but the possibility of acute respiratory failure
encourages early intervention. Neurologic symptoms typi-
cally present in the early stages after the development of
respiratory distress. These changes vary widely, from mild
confusion and drowsiness to obtundation or seizures. The
petechial rash is least common, and usually the last sign to
manifest. It most commonly arises in the head, neck, axillae,
and anterior thorax.
MACROSCOPIC AND MICROSCOPIC FEATURES
Despite the well-known clinical characterization, debate
exists within the literature regarding the most appropriate
clinical diagnostic criteria for FES. Therefore, some forensic
pathologists are cautious about making a postmortem
diagnosis of FES, especially in cases where clinical
information is limited.30 Nevertheless, FES does have
unique autopsy features that aid in diagnosis, with a
predilection for lung, brain, kidney, skin, and eye. Gross
pulmonary findings may include increased lung weight and
volume, as well as firm but not solid texture, with a marbled
appearance of the visceral pleura due to alternating areas of
hemorrhage. Tardieu spots (petechiae or ecchymoses) may
be present beneath the visceral pleura.31 Although micro-
scopic evaluation for fat emboli with routine hematoxylin-
eosin is often unrevealing (Figure 1), if the pathologist is
sensitive to the differential of FES and is assessing for it,
oftentimes he or she may see intravascular round/ovoid
negative staining suggestive of possible fat emboli. With
enough suspicion, special staining may prove useful. Thin
slices of lung tissue fixed in formalin can be postfixed and
stained in osmium tetroxide solution and subsequently
submitted for paraffin embedding. Fat emboli will appear as
round, uniform, black-staining droplets within blood vessels
(Figures 2 and 3). Alternatively, oil red O staining can be
used, but only on frozen section tissue, as lipids are
dissolved by xylene and alcohol solvents during standard
tissue processing.
Central nervous system gross pathology in FES includes
potentially innumerable, macroscopic, brown-red petechial
hemorrhages that are produced by fat emboli to the brain,
Liposuction-Induced Fat Embolism Syndrome—Cantu & Pavlisko

Figure 1. Histopathology of lung parenchyma taken at autopsy of a
patient with suspected fat embolism syndrome (hematoxylin-eosin,
original magnification 340).
Figure 2. Lung parenchyma with multiple fat emboli (hematoxylin-
eosin with osmium tetroxide overstaining, original magnification 310).
Figure 3. Lung parenchyma with intravascular fat embolus (hematox-
ylin-eosin with osmium tetroxide overstaining, original magnification
340).
and are particularly restricted to the white matter and spinal
cord, with possible limited extension into gray matter
(Figure 4). The petechiae may vary from 4 mm to less than
1 mm. Hemorrhage may also be present, but is less
common, and is found in the cerebral gray matter, brain
stem, and cerebellum. Microscopic brain findings with
Arch Pathol Lab Med—Vol 142, July 2018
routine hematoxylin-eosin will show the corresponding
petechial cerebral white matter and/or spinal cord hemor-
rhages (Figures 5 and 6) and cerebrospinal vascular fat
emboli (Figure 7).
Renal findings are generally unremarkable grossly.
Furthermore, kidney function tests and renal parenchyma
are not typically affected by fat emboli. Rather, renal
glomeruli harbor the disease burden because of the large
blood supply of the kidneys and the restriction of the
capillary bed to the glomeruli. Hematoxylin-eosin staining
shows fat droplet deposition in arterioles/capillaries and
renal glomeruli. These observations can be further empha-
sized utilizing the aforementioned fat-specific staining
methods.
Cutaneous manifestations are produced by fat emboliza-
tion to small dermal capillaries that cause erythrocyte
extravasation. Macroscopically, this correlates to a petechial
rash of the anterior thorax, axillae, neck, oral mucosa, and
conjunctiva.
LABORATORY AND IMAGING FINDINGS
Acute decrease in hematocrit, increase in serum lipase
levels, hypofibrinogenemia, hypoxemia, thrombocytopenia
(50% of patients), anemia (70% of patients), and hypocal-
cemia (due to free fatty acid binding to calcium) typically
occur, if present, at the same time as clinical manifestations
(24–72 hours after initial insult).24,32 Although these
laboratory findings frequently occur in the settings of FES,
they are not specific.
Chest radiographs typically appear normal early in the
disease process, but gradual (1–3 days) progression to
bilateral flocculent shadows, and possibly bilateral intersti-
tial opacification, occurs in some cases. The radiologic signs
may remain for up to 3 weeks.32 Computed tomography
imaging of the chest generally shows focal areas of ground-
glass opacification with interlobular septal thickening.
However, ill-defined centrilobular and subpleural nodules
representing alveolar edema, microhemorrhage, and in-
flammatory response secondary to ischemia and cytotoxic
emboli may be observed.24
Computed tomography imaging of the brain, an initial
modality used because of neurologic impairment, may show
no abnormalities, or it may show diffuse white matter
petechial hemorrhages, consistent with microvascular dam-
age. Rarely, it can show generalized cerebral edema or
atrophy in severe cases of FES. Magnetic resonance imaging
may be useful in patients who present with neurological
features of fat embolism but with a normal computed
tomography brain image. T2-weighted images show scat-
tered high–signal-intensity lesions early in the disease
course, typically deep in the white matter, cerebellum, and
brain stem.24
DIFFERENTIAL DIAGNOSIS
The differential diagnosis in a patient with signs and
symptoms resembling FES is exhaustive because of the
nonspecific and variable presentation. Primary consider-
ations should be based upon the specific clinical presenta-
tion, which may or may not present with the typical triad.
Respiratory insufficiency in isolation should prompt suspi-
cion for postsurgical pulmonary thromboembolism, pneu-
monia, drug reaction, cardiogenic pulmonary edema, and
FES. Imaging modalities are typically helpful to differentiate
pulmonary thromboemboli from fat emboli. Computed
Liposuction-Induced Fat Embolism Syndrome—Cantu & Pavlisko 873
Figure 4. Petechial hemorrhages of cerebral white matter (gross image).
Figure 5. Multiple petechial hemorrhages of the spinal cord (hematoxylin-eosin, original magnification 32).
Figure 6. Multiple petechial hemorrhages shown at higher magnification as targetoid lesions, an area where a cerebral vessel was infiltrated by fat
and subsequently necrosed (hematoxylin-eosin, original magnification 310).
Figure 7. Arachnoid arteriole showing occlusion by fibrin and adipocytes (hematoxylin-eosin, original magnification 340).
tomography imaging, the gold-standard imaging modality
of pulmonary thromboembolism, may be contraindicated in
patients who cannot tolerate intravenous contrast. Ventila-
tion perfusion scanning can detect areas of perfusion
failures, but it does not reliably differentiate thromboem-
bolism from FES.
Meningococcal septicemia may present with neurologic
impairment and skin changes, but respiratory insufficiency
would be unusual and would assist in excluding this disease.
Patients who present primarily with neurologic manifesta-
tions (and limited respiratory insufficiency) should prompt
evaluation for cranial hemorrhage. Noncontrast head
computed tomography is a valuable tool to help rule such
diagnoses in or out.
CURRENT TREATMENT AND PROGNOSIS
Treatment of FES is merely supportive, as there is no
directed therapy. Thus, prevention, early detection, and
prompt supportive therapy are critical. Early diagnosis not
only limits morbidity and mortality, but also diminishes
additional investigation cost burdens. Continuous positive
airway pressure is usually the first-line treatment for
respiratory insufficiency. This treatment generally fails
quickly, and swift transition to intubation with mechanical
874 Arch Pathol Lab Med—Vol 142, July 2018
ventilation and positive end expiratory pressure should be
provided. Pharmacologic agents can be used to maintain
hemodynamic stability. Heparin and ethyl alcohol were
historically used for treatment, but they are ineffective and
are rarely used today. Contrary to recent efforts, there are
insufficient data to support the routine use of corticoste-
roids, aspirin, and prophylactic antibiotics.24
Fat embolism syndrome is a self-limiting disease. The
overall mortality from FES after liposuction is approximately
10% to 15%, and mortality correlates with severity of
respiratory insufficiency.32 Although the duration of FES is
difficult to predict, survival beyond initial presentation
generally leads to full recovery.
References
1. Zenker F. Beitrage zur Anatomie und Physiologie de Lung. Dresden,
Germany: J. Braunsdorf; 1861.
2. Nichols GR 2nd, Corey TS, Davis GJ. Nonfracture-associated fatal fat
embolism in a case of child abuse. J Forensic Sci. 1990;35(2):493–499.
3. Christman KD. Death following suction lipectomy and abdominoplasty.
Plast Reconstr Surg. 1986;78(3):428.
4. American Society for Aesthetic Plastic Surgery. 2015 cosmetic surgery
national data bank statistics. http://www.surgery.org/sites/default/files/ASAPS-
Stats2015.pdf. Accessed January 25, 2017.
5. Abbes M, Bourgeon Y. Fat embolism after dermolipectomy and liposuction.
Plast Reconstr Surg. 1989;84(3):546–547.
Liposuction-Induced Fat Embolism Syndrome—Cantu & Pavlisko
 6. Boezaart AP, Clinton CW, Braun S, Oettle C, Lee NP. Fulminant adult
respiratory distress syndrome after suction lipectomy: a case report. S Afr Med J.
1990;78(11):693–695.
7. Byeon SW, Ban TH, Rhee CK. A case of acute fulminant fat embolism
syndrome after liposuction surgery. Tuberc Respir Dis (Seoul). 2015;78(4):423–
427.
8. Costa AN, Mendes DM, Toufen C, Arrunategui G, Caruso P, de Carvalho
CR. Adult respiratory distress syndrome due to fat embolism in the postoperative
period following liposuction and fat grafting. J Bras Pneumol. 2008;34(8):622–
625.
9. de Lima ESR, Apgaua BT, Milhomens JD, et al. Severe fat embolism in
perioperative abdominal liposuction and fat grafting. Braz J Anesthesiol. 2016;
66(3):324–328.
10. Dillerud E. Abdominoplasty combined with suction lipoplasty: a study of
complications, revisions, and risk factors in 487 cases. Ann Plast Surg. 1990;
25(5):333–338; discussion 339–343.
11. Erba P, Farhadi J, Schaefer DJ, Pierer G. Fat embolism syndrome after
combined aesthetic surgery. J Plast Surg Hand Surg. 2011;45(1):51–53.
12. Fourme T, Vieillard-Baron A, Loubieres Y, Julie C, Page B, Jardin F. Early fat
embolism after liposuction. Anesthesiology. 1998;89(3):782–784.
13. Laub DR Jr, Laub DR. Fat embolism syndrome after liposuction: a case
report and review of the literature. Ann Plast Surg. 1990;25(1):48–52.
14. Platt MS, Kohler LJ, Ruiz R, Cohle SD, Ravichandran P. Deaths associated
with liposuction: case reports and review of the literature. J Forensic Sci. 2002;
47(1):205–207.
15. Ross RM, Johnson GW. Fat embolism after liposuction. Chest. 1988;93(6):
1294–1295.
16. Rothmann C, Ruschel N, Streiff R, Pitti R, Bollaert PE. Fat pulmonary
embolism after liposuction [in French]. Ann Fr Anesth Reanim. 2006;25(2):189–
192.
17. Scroggins C, Barson PK. Fat embolism syndrome in a case of abdominal
lipectomy with liposuction. Md Med J. 1999;48(3):116–118.
18. Wessman DE, Kim TT, Parrish JS. Acute respiratory distress following
liposuction. Mil Med. 2007;172(6):666–668.
Arch Pathol Lab Med—Vol 142, July 2018
19. Zeidman M, Durand P, Kundu N, Doumit G. Fat embolism after liposuction
in Klippel-Trenaunay syndrome. J Craniofac Surg. 2013;24(4):1319–1321.
20. Cantu CA, Pavlisko EN. Liposuction-induced fat embolism syndrome. BMJ
Case Rep. April 18, 2017. doi:10.1136/bcr-2017/219835.
21. El-Ali KM, Gourlay T. Assessment of the risk of systemic fat mobilization
and fat embolism as a consequence of liposuction: ex vivo study. Plast Reconstr
Surg. 2006;117(7):2269–2276.
22. Fabian TC. Unravelling the fat embolism syndrome. N Engl J Med. 1993;
329(13):961–963.
23. Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Brief
report: fulminating fat embolism syndrome caused by paradoxical embolism
through a patent foramen ovale. N Engl J Med. 1993;329(13):926–929.
24. Jain S, Mittal M, Kansal A, Singh Y, Kolar PR, Saigal R. Fat embolism
syndrome. J Assoc Physicians India. 2008;56:245–249.
25. Hulman G. Pathogenesis of non-traumatic fat embolism. Lancet. 1988;
1(8599):1366–1367.
26. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br.
1974;56B(3):408–416.
27. Talbot M, Schemitsch EH. Fat embolism syndrome: history, definition,
epidemiology. Injury. 2006;37(suppl 4):S3–S7.
28. Carr JB, Hansen ST. Fulminant fat embolism. Orthopedics. 1990;13(2):
258–261.
29. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome: a
10-year review. Arch Surg. 1997;132(4):435–439.
30. Miller P, Prahlow JA. Autopsy diagnosis of fat embolism syndrome. Am J
Forensic Med Pathol. 2011;32(3):291–299.
31. Emson HE. Fat embolism studied in 100 patients dying after injury. J Clin
Pathol. 1958;11(1):28–35.
32. Wang HD, Zheng JH, Deng CL, Liu QY, Yang SL. Fat embolism syndromes
following liposuction. Aesthetic Plast Surg. 2008;32(5):731–736.
33. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;
52(4):732–737.
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