1. health and fitness
2. disease

Fat Embolism Syndrome
Dr. Alex Rabinovich
Introduction
• Zenker (Pathologist) first identified fat
embolism syndrome (FES) at autopsy in
1862.
• von Bergmann was the first physician to
identify FES clinically in 1873.
• Initial clinical description was respiratory
and neurological manifestations with
petechial hemorrhages.
Introduction
• Most commonly associated with LONG BONE
(Femur, Tibia, Humerus, …), PELVIC and
SPINAL #’s
• More frequent in CLOSED > OPEN #’s
• Younger pt’s (more bone marrow) > Older Pt’s
• A single long bone # has 1-5% chance of
developing FES, this directly correlates with the
number of long bone #’s
• FES has been reported as high as 33% in
bilateral femoral fractures.
Introduction
Pathophysiology
• 2 Theories
• Mechanical vs. Biochemical
• Mechanical
– Fat globules from disrupted bone marrow or adipose
tissue are forced into torn venules in areas of trauma.
• Biochemical
– Hormonal changes caused by trauma and/or sepsis
induce systemic release of free fatty acids (FFA) as
chylomicrons which cause the systemic FES.
Pathophysiology
• Mechanical
– Fractures of marrow-containing bone (Femur,
Pelvis) have the highest incidence of FES and
cause the largest volume of fat emboli,
because the disrupted venules in the marrow
remain tethered open by their osseous
attachments.
– The marrow contents enter the venous
circulation with little difficulty.
Pathophysiology
• Mechanical
– This theory is supported by research on
Orthopaedic long bone (IM reaming) and
spinal surgeries which cause fat globules to
enter the blood circulation when vigorous
reaming/fixation is done.
– Increased Pressure + Volume Æ
Extravasation
– Measuring fat globules pre and post reaming
shows significant difference in concentration.
Pathophysiology
• Mechanical
– But what makes this clinically significant?
– Fat droplets are deposited in the pulmonary capillary
beds and travel through arteriovenous shunts to the
brain. Systems affected include LUNG, BRAIN and
CIRCULATION.
– Microvascular lodging of droplets produces local
ischemia and inflammation, with concomitant release
of inflammatory mediators, platelet aggregation, and
vasoactive amines.
Pathophysiology
• Biochemical
– FES is dependent upon degradation of the embolized
fat into free fatty acids.
– Neutral fat does not cause an acute lung injury, it is
hydrolyzed over the course of hours to several
products, including FFA, which cause ARDS in animal
models.
– CRP (acute phase reactant), which is elevated in
trauma patients, appears to be responsible in lipid
agglutination (FES) for both traumatic and nontraumatic FES.
Pathophysiology
• Biochemical
– The process of Neutral fat cells -> FFA ->
Agglutination with CRP may explain the time
sequence of clinical findings in FES.
– Onset of symptoms may coincide with
Agglutination.
– This theory is animal model based and
circumstantial at best.
Clinical
• Diagnosis is made clinically NOT
chemically. It does not matter how much
fat globules are in your circulation, it just
matters if you have their side effects.
• FES typically manifests 24 to 72 hours
after the initial insult. Rarely <12 hrs or
>72 hrs.
• Classic triad: Hypoxemia; Neurologic
abnormalities; and a Petechial Rash
Clinical
• SOB, Inc RR, Hypoxemia are early findings.
50% of pt’s with symptoms will need ventilation
support. Respiratory dysfunction is major cause
of mortality, which is about 10-20%.
• Neurologic symptoms usually develop after lung
injury, and include: Confusion, altered LOC,
Headaches, +/- Seizures, +/- Strokes with Focal
Deficits.
• Petechial rash is usually a late finding
(frequency of 20-50% of pt’s). Head, neck,
anterior thorax, subconjunctiva, and axillae are
most common regions.
Clinical
• Petechiae result from the occlusion of dermal
capillaries by fat globules, leading to
extravasation of erythrocytes.
• No abnormalities of platelet function have been
documented.
• The rash resolves in five to seven days.
• Other Findings
–
–
–
–
–
Scotomata (Purtscher's retinopathy)
Lipiduria
Fevel
Coagulation Abnormalities (DIC like)
Myocardial Depression
Diagnosis
• FES is clinical diagnosis
• CXR (n) mostly. Some have patchy
consolidations at periphery or bases due to
alveolar hemorrhages, but not sensitive nor
specific (snow storm pattern).
• Ventilation/perfusion scans may demonstrate a
mottled pattern of subsegmental perfusion
defects with a normal ventilatory pattern.
• Focal areas of ground glass opacification with
interloblar septal thickening are generally seen
on chest CT
• MRI of the brain may reveal high intensity T2
signal, which correlates with the degree of
clinical neurologic impairment
Diagnosis
• Common misconception that the presence of fat
globules, either in sputum, urine, or a wedged
PA catheter, is necessary to confirm the
diagnosis of FES
• In 50% of fracture patients, fat globules was
demonstrated in the serum, without symptoms of
FES.
• HOWEVER
• Growing literature on the use of bronchoscopy
with bronchoalveolar lavage to detect fat
droplets in alveolar macrophages as a means to
diagnose fat embolism. Sensitivity and specificity
are unknown, being studied in Trauma patients.
Diagnosis – Classic Gurd’s criteria
• 1 major criteria and at least 4 minor criteria
Major Criteria
• PaO2 < 60mmHg &
FiO2 >40%
• Altered mentation
• Petechial rash
Minor Criteria
• Temp > 38.5 0C
• HR > 120/min
• PLTs < 150 X 109/L
• Retinal fat emboli
• Oliguria/anuria
• Fat globules in urine
• ↓ HCT not attributed to
blood loss or IVF dilution
• Fat macroglobulemia
Treatment
• ATLS protocol
• High clinical suspicion during 3rd survey
1. Early immobilization of fracture and early
definitive reduction (open or closed).
2. Maintain intravascular volume to
maintain cardiovascular stability
(hypovolemic shock resuscitation), may
use colloids (albumin) as it can expand
fluid and bind FFA.
3. Mechanical ventilation with PEEP
Treatment
4. IV Ethanol has been used in Russia,
Europe and some American centres to
decrease rate of FES.
J Bone Joint Surg Am. 1977 Oct;59(7):878-80
“A raised level of alcohol in the blood
was associated with a lower incidence of
fat embolism” all other variables
controlled.
Other studies
Can J Surg. 1970 Jan;13(1):41-9
Br Med J. 1978 May 13;1(6122):1232-4
Treatment
5. Corticosteroids (controversial)
•
•
•
•
Surg Gynecol Obstet. 1978 Sep;147(3):358-62
Ann Intern Med. 1983 Oct;99(4):438-43
J Trauma. 1987 Oct;27(10):1173-6
J Bone Joint Surg [Br] 1987 Jan;69(1):128-31
•
•
•
Methylprednisolone is the study drug
Randomized double blind studies
Specific to fractures and all other variables
controlled. RCT’s with control drugs.
Differences was dosing and timing of drug
admin.
Major S/E looked at: GI Bleeds, Infections,
Delayed healing, Cortisol issues, and CVS
stability (cardiac mostly), Mortality
•
•
Treatment
5. Corticosteroids
12 doses
•
•
•
•
•
•
Other doses: 1.5 mg/kg q8h X 48 hrs
Statistical Significance in reduction of clinical diagnosed FES
No major complications were noted
Potential for complications is the major concern (bleeds, infection,
cardiac compromise)
Key is to initiate treatment early and for a short period of time
Be cautious of the S/E
Treatment
• The overall outcomes of FES with respect to
isolated long bone, pelvis and spine fractures is
good with standard immobilization and reduction
of fracture, fluid resuscitation and ventilator
support as needed.
• Steroids and Ethanol treatments can be adjuncts
to treatment, but most be started early.
Recommended to start with low dose and for a
period of 24-48 hours.
• No evidence on Steroids or Ethanol Tx once
FES is diagnosed. This is only for Prophylaxis
Almost Over
• Now that you have learned the basics of
FES.
• Its time for your final exam
Questions
•
What percentage of people with skeletal
trauma would normally develop fat emboli, and
what percentage of these would then develop
the Fat Embolism Syndrome?
1.
2.
3.
4.
30% and 12%
50% and 10%
70% and 1%
90% and 5%
Questions
•
What percentage of people with skeletal
trauma would normally develop fat emboli, and
what percentage of these would then develop
the Fat Embolism Syndrome?
1.
2.
3.
4.
30% and 12%
50% and 10%
70% and 1%
90% and 5%
Questions
• How does fat emboli enter the systemic
circulation (arterial vs. venous)?
Questions
• How does fat emboli enter the systemic
circulation (arterial vs. venous)?
• Patent Foramen Ovale
Questions
• What percentage of the general
population are considered to have a
patent foramen ovale?
•
•
•
•
5%
15%
25%
40%
Questions
• What percentage of the general
population are considered to have a
patent foramen ovale?
•
•
•
•
5%
15%
25%
40%
Questions
•
A biochemical theory suggests that a chemical event
during trauma, or during the activation of the stress
response, affects the solubility of circulating lipids
causing them to coalesce and form systemic emboli.
These emboli travel to lungs, brain and skin to give the
FES triad of signs.
There are some very unusual causes of FES in the nontrauma patients, including the strikingly unusual:
liposuction, chemotherapy, renal transplant.
1. True
2. False
Questions
•
A biochemical theory suggests that a chemical event
during trauma, or during the activation of the stress
response, affects the solubility of circulating lipids
causing them to coalesce and form systemic emboli.
These emboli travel to lungs, brain and skin to give the
FES triad of signs.
There are some very unusual causes of FES in the nontrauma patients, including the strikingly unusual:
liposuction, chemotherapy, renal transplant.
1. True
2. False
Questions
•
The pulmonary signs are usually noted first and include
tachypnoeia, dyspnoea and cyanosis. These signs
result from the embolic fat being hydrolised by lung
lipase with the release of lung-toxic FFA. These FFAs
induce an acute lung injury and subsequent ARDS.
•
This process accounts for the time period between
injury and onset of clinical signs of FES. Time period is
usually:
1.
2.
3.
4.
6 to 12 hours
12 to 24 hours
24 to 72 hours
72 to 84 hours
Questions
•
The pulmonary signs are usually noted first and include
tachypnoeia, dyspnoea and cyanosis. These signs
result from the embolic fat being hydrolised by lung
lipase with the release of lung-toxic FFA. These FFAs
induce an acute lung injury and subsequent ARDS.
•
This process accounts for the time period between
injury and onset of clinical signs of FES. Time period is
usually:
1.
2.
3.
4.
6 to 12 hours
12 to 24 hours
24 to 72 hours
72 to 84 hours
Questions
•
•
The cutaneous signs are usually seen within 72
hours. On a critically ill patient they may go
unnoticed, thereby losing the chance for
confirmation of diagnosis.
The rash is usually seen on:
1.
2.
3.
4.
Thighs / Calves / Ankles
Clustered around the fracture site
Chest / Axilla / Conjunctiva
Back of the head and knees
Questions
•
•
The cutaneous signs are usually seen within 72
hours. On a critically ill patient they may go
unnoticed, thereby losing the chance for
confirmation of diagnosis.
The rash is usually seen on:
1.
2.
3.
4.
Thighs / Calves / Ankles
Clustered around the fracture site
Chest / Axilla / Conjunctiva
Back of the head and knees
Questions
•
•
1.
2.
3.
4.
Cerebral signs are non-specific, very rarely focal:
headache, irritability and delirium. Severe cases may
show coma and convulsions. These signs are produced
by embolism of fat through a patent foramen ovale and
subsequent microvascular occlusion of the brain
circulation by fat.
Embolic fat can produce the necessary right heart
pressures to open a patent foramen ovale but what is
another causative factor?
Increased cardiac pressures from ventilation
Pneumothorax or haemothorax
Poor positioning on the OR table
Pressure exerted on the chest by OR equipment
Questions
•
•
1.
2.
3.
4.
Cerebral signs are non-specific, very rarely focal:
headache, irritability and delirium. Severe cases may
show coma and convulsions. These signs are produced
by embolism of fat through a patent foramen ovale and
subsequent microvascular occlusion of the brain
circulation by fat.
Embolic fat can produce the necessary right heart
pressures to open a patent foramen ovale but what is
another causative factor?
Increased cardiac pressures from ventilation
Pneumothorax or haemothorax
Poor positioning on the OR table
Pressure exerted on the chest by OR equipment
Questions
•
•
Diagnosis is always made on clinical grounds, there is no specific
"test" for FES. Various sets of criteria exist to make the diagnosis
more accurate, such as those of Gurd & Wilson or those of
Vedrienne, Guillaume and Gagnieu.
Management is then supportive as there is no specific treatment of
the FES. Guidelines for the management of FES would include:
1. Prompt immobilisation of the fracture / delayed internal fixation of
the fracture / early use of steroids / early use of Heparin
2. Prompt immobilisation of the fracture / early internal fixation of the
fracture / prompt treatment of hypoxia / maintenance of cardiac
output
3. Prompt immobilisation of fracture / intraoperative surgical
embolectomy / early use of IV Ethanol / daily low dose Aspirin
4. Prompt immobilisation of the fracture / avoidance of intramedullary
nails / early use of steroids / mandatory use of calf compressors
Questions
•
•
Diagnosis is always made on clinical grounds, there is no specific
"test" for FES. Various sets of criteria exist to make the diagnosis
more accurate, such as those of Gurd & Wilson or those of
Vedrienne, Guillaume and Gagnieu.
Management is then supportive as there is no specific treatment of
the FES. Guidelines for the management of FES would include:
1. Prompt immobilisation of the fracture / delayed internal fixation of
the fracture / early use of steroids / early use of Heparin
2. Prompt immobilisation of the fracture / early internal fixation of
the fracture / prompt treatment of hypoxia / maintenance of
cardiac output
3. Prompt immobilisation of fracture / intraoperative surgical
embolectomy / early use of IV Ethanol / daily low dose Aspirin
4. Prompt immobilisation of the fracture / avoidance of intramedullary
nails / early use of steroids / mandatory use of calf compressors
Questions
•
A Pulmonary Artery Catheter is often inserted to
facilitate the use of inotropic agents and fluids in a
critically ill patient with FES. Bearing in mind that there
will be widespread microvascular occlusion with fat in
the pulmonary vasculature what would be the most
typical finding?
1.
2.
3.
4.
A high Systemic Vascular Resistance (SVR)
A low Systemic Vascular Resistance (SVR)
A high Pulmonary Vascular Resistance (PVR)
A low Pulmonary Vascular Resistance (PVR)
Questions
•
A Pulmonary Artery Catheter is often inserted to
facilitate the use of inotropic agents and fluids in a
critically ill patient with FES. Bearing in mind that there
will be widespread microvascular occlusion with fat in
the pulmonary vasculature what would be the most
typical finding?
1.
2.
3.
4.
A high Systemic Vascular Resistance (SVR)
A low Systemic Vascular Resistance (SVR)
A high Pulmonary Vascular Resistance (PVR)
A low Pulmonary Vascular Resistance (PVR)
Questions
•
A patient who does not develop a
petechial rash by day 2 or 3 on his or her
chest, anterior axillary folds or
conjunctiva does not have either Fat
Embolism or Fat Embolism Syndrome.
1. True
2. False
Questions
•
A patient who does not develop a
petechial rash by day 2 or 3 on his or her
chest, anterior axillary folds or
conjunctiva does not have either Fat
Embolism or Fat Embolism Syndrome.
1. True
2. False
The END
•
Thank you
• References
1. UpToDate website
2. eMedicine website