Current Anaesthesia & Critical Care 21 (2010) 277e281

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Current Anaesthesia & Critical Care

journal homepage: www.elsevier.com/locate/cacc

POINTS OF VIEW

Fat embolism e An update

Pratik Sinha, Nick Bunker*, Neil Soni
Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK

s u m m a r y
Keywords: Fat embolism syndrome is an unexpected and alarming complication that is difficult to actively prevent,
Incidence hard to diagnose with confidence and has limitations in effective treatment modalities. The syndrome is
Aetiology
a melange of respiratory, haematological, neurological and cutaneous symptoms and signs associated
Pathophysiology
Diagnosis
with trauma and other disparate surgical and medical conditions. The pathogenesis is still debated. It is
Treatment clear that fat emboli are quite common yet the clinical syndrome is rare. Diagnosis is by pattern
recognition as befits a syndrome, but the recently defined features on MRI could now be used to increase
the probability of the diagnosis. Various therapeutic options have been tried and failed. At present
steroids have a single meta-analysis suggesting benefit but it is in the trauma population where they may
be contra indicated for other reasons, i.e. infection, so their place is ill defined. Supportive treatment is
the mainstay.
Ó 2010 Elsevier Ltd. All rights reserved.

1. Definition 2.1. Fat embolus theory: mechanical

It is important to differentiate fat in the circulation and the
syndrome that is sometimes seen as a consequence. Fat in the
circulation is probably quite common and embolisation can occur.
Fat embolism syndrome (FES) is when there is fat in the circulation
and it is associated with an identifiable clinical pattern of symp-
toms and signs.
The classic description of the syndrome is the combination of
respiratory failure associated with neurological disturbance and
a petechial rash often in the absence of any obvious cause.
2. Pathophysiology
The mechanism of fat embolism syndrome is not clear. It is clear
that fat frequently gets into the circulation and can be demon-
strated on both sides of the circulation. It is clear that fat can cause
embolisation. Yet the syndrome is relatively uncommon. As
a syndrome the range of effects implies diffuse damage at more
than one site. This could be due to embolisation or may be asso-
ciated with a different secondary mechanism. It is hard to tie all the
effects seen in FES to embolus as a sole mechanism. Several theories
have been postulated but the two main contenders are the
mechanical and biochemical theories.
* Corresponding author.
E-mail address: nickbunker@doctors.net.uk (N. Bunker).
Fat globules can be physically forced into the venous system
during trauma. In surgical situations high pressures are exerted in
the marrow and this may force fat into the blood stream. The
normal marrow pressure is 30e50 mmHg but this can be dramat-
ically increased (up to 800 mmHg) during intra-medullary reaming
and insertion of intra-medullary devices.1 The presence of fat micro
emboli can be clearly shown with ultrasonography in a relatively
high percentage of patients albeit they are micro emboli and in
small numbers.2,3 Micro emboli seem to be seen most during
manipulation of the intra-medullary cavity. Circumstantial
evidence for the importance of intra-medullary fat comes from the
observation that in previously reamed femoral cavities during redo
replacements the incidence is low.4 The use of cement is also
associated with fat embolic phenomena but it is also seen in
cement-less prosthesis.5 Various models of fat injection or sub-
jecting the medullary marrow to high pressures can all be shown to
produce emboli and to result in cardiorespiratory problems. It has
also been shown that the use of external fixation in trauma is
associated with a lower incidence of FES than intra-medullary
fixation.6
2.2. Free fatty acid theory: biochemical
This is in two parts. The first is the theory that trauma results in
the release of lipases into the plasma that destabilise circulating fat
molecules resulting in their saponification and de-emulsification.
In animal studies exogenous fat in the circulation has been shown

0953-7112/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.cacc.2010.03.003
278 P. Sinha et al. / Current Anaesthesia & Critical Care 21 (2010) 277e281
to cause the release of phospholipase A2, methylguanidine and
proinflammatory cytokines. The significance of this phenomenon
in vivo is unknown. In the same model fat droplets and fibrin
thrombi were found in several organs.7
A more appealing biochemical theory invokes the histotoxic
effects of free fatty acids (FFA). It is known that FFA’s can cause
severe vasculitis in animal models and in the lung this can disrupt
pulmonary architecture fairly rapidly. If the free fatty acids are near
the endothelium they can cause disruption of the integrity of the
endothelial membrane and capillary wall leading to haemorrhage
and oedema. Although bone marrow is predominantly neutral fat,
in the acute inflammatory milieu it is possible that FFA activity may
be important.8e10 If in vivo there is hydrolysis of neutral fats to
FFA’s it could explain the interval before the probable time of fat
release and the onset of signs and symptoms. In the clinical setting
following long bone surgery FFA levels were found to be signifi-
cantly higher in patients with multiple injuries and associated with
significantly lower oxygen tension.11
2.3. Thrombocytopaenia
Part of the syndrome is often a falling platelet count. In the
trauma population with hypovolaemia and coagulopathy there may
be an association between sluggish, hypoxaemic circulation and
possible ‘sludging’ of blood.12 Coagulation abnormalities are
encountered frequently in FES. The combination of activation of
platelets, vascular endothelial effects and microaggregate collec-
tion might be catalysed by the presence of fat.
2.4. Systemic and paradoxical embolisation
Given that fat is released into the venous return to the right
heart, it is a curiosity that it causes systemic effects, sometimes
without pulmonary effects.13,14 It has been suggested that this
could be via a patent foramen ovale (PFO) which is not uncommon
in the general population, with an incidence of about 25%.15
Although closure of PFO does reduce emboli, whether a PFO was
present or not makes no difference to the incidence of FES and it is
clear that emboli are seen in patients without PFO.3,16e18 Trans-
pulmonary systemic fat embolisation does occur and has been
shown in dogs without a patent foramen ovale.19 The size and
deformability of the fat micelles may allow this pulmonary transit.
There is no clear individual mechanism that can readily explain
all the abnormalities seen in the syndrome. As shall be discussed
later the distribution of lesions on cerebral MRI might provide clues
towards multiple mechanisms but to date it is conjecture.
3. Clinical features of the syndrome
3.1. Associations
There are several reported causes of fat embolism syndrome.
These are listed below and may be considered as preconditions
where fat embolism syndrome (FES) might be seen. Trauma with
long bone fractures and major elective orthopaedic procedures are
the most common causes. Other causes are rarer. Liposuction has
the potential to force fat into the circulation and there are many
case reports of it causing Fat Embolism Syndrome (FES). Medical
conditions such as hepatic necrosis or the fatty liver may predis-
pose. Drugs such as intralipid,, parenteral nutrition or propofol
have the potential to cause the syndrome although the mechanisms
may differ in that the fat emulsions may coalesce and cause
mechanical obstruction of the vascular tree and hence local
damage. FES is implicated in sickle cell disease. In an acute sickle
crisis the pulmonary macrophages often stain positive for fat and
Bronchoalveolar Lavage may be a useful adjunct to diagnosis.20
Bone marrow necrosis may release fat and certainly non-specific
markers such as lipases are raised. In a recent study the incidence
appeared very high (33%).20e22
Main causes
Trauma e long bone fractures
Joint replacements e prosthetic placement
Scoliosis surgery
Mechanical disruption of adipocytes
Soft tissue injury. (Crush and Blast injuries)
Liposuction
Liver failure e fatty liver.
Mechanical disruption of the bone marrow
Bone marrow harvest
Bone marrow transplant
Exogenous fat
Parenteral nutrition
Propofol infusion
Lymphograophy
Non-specific
Burns
Extra corporeal circulation
Acute sickle crisis
Acute pancreatitis
Decompression sickness
Altitude sickness
3.2. Diagnosis
Fat embolism syndrome is a collection of symptoms and signs.
As with any syndrome it is a clinical pattern rather than an easily
defined entity. It is helpful to consider the condition in terms of
preconditions that need to exist, symptoms that may occur and
physical signs that may or may not be present and to a lesser or
greater degree. It may even then be a diagnosis of exclusion as it
overlaps with other conditions.
While many of the signs may be suggestive of the condition,
none are absolutely pathognomonic.
It is also important to emphasise the wide range of clinical
presentation from almost imperceptible sub-clinical signs to the
more common gradual onset or the fulminating crisis with
pulmonary and systemic embolisation of fat, right ventricular
failure and cardiovascular collapse.
FES can present in a fulminant manner after the trauma or
during the operation. The more classical onset is gradual over
12e36 h following injury or surgery, with increasing hypoxaemia
often associated with neurological symptoms such as confusion,
drowsiness, or coma. It may be accompanied by fever and a char-
acteristic petechial rash, often in the axillae but may be on the face
or in the conjunctivae.
To diagnose this syndrome requires the right preconditions to
exist (see associations above). Gurd’s classification is helpful and
can be seen in Table 1.
In order to diagnose FES, 1 major and 4 minor criteria are
required. Although various reports describe the presence of fat
globules in the blood or sputum this requirement poses several
problems. While the original guidelines require daily testing for fat
globules it has been contentious. Fat globules can be found in both
trauma patients and more worryingly in healthy volunteers with no
 P. Sinha et al. / Current Anaesthesia & Critical Care 21 (2010) 277e281
Table 1
Modified from Gurd.23
Major criteria Petechial rash
Respiratory symptoms e tachypnoea, dyspnoea,
bilateral inspiratory crepitations, haemoptysis,
bilateral diffuse patchy shadowing on chest X-ray
Neurological e confusion, drowsiness, coma
Minor criteria Tachycardia > 120 beat minr1
Pyrexia > 39.4
Retinal changes e fat or petechiae
Renal changes e anuria or oliguria
Jaundice
Laboratory (minor) Thrombocytopaenia > 50% decrease on admission value
Sudden decrease in haemoglobin level > 20%
of admission value
High erythrocyte sedimentation rate > 71 mm hr1
Fat macroglobulaemia
Fat in sputum
suggestion of FES. It is clearly relatively non-specific. Pragmatically
it is also difficult to get the laboratory to look for fat. Hence the
modified Gurd’s classification may represent a more clinically
relevant system.
Lindeque suggested a more specific approach to the lung
component of FES which measures functional aspects of the lung
injury. These are very similar to those used for any other form of
lung injury.
Pulmonary criteria for FES e Lindeque.24
1 A sustained Pao2 of less than 8 kPa (Fio2 0.21).
2 A sustained Paco2 of more than 7.3 kPa or pH of less than 7.3.
3 A sustained respiratory rate of greater than 35 breaths.minr1
even after adequate sedation.
4 Increased work of breathing judged by dyspnoea, use of
accessory muscles, tachycardia and anxiety.
The incidence of the condition is difficult to identify. The
retrospective reported incidence tends to be low with many less
than 1% but with a few as high as 4%. Prospective studies report a far
higher incidence of 11e19%. This is not as high as the incidence of
fat embolisation at post mortem where evidence of fat is very
common but not necessarily associated with the syndrome itself.
4. Presentation
Most patients, more than 70%, have a significant respiratory
component25 but this can be very variable, ‘not all respiratory
failure following orthopaedic surgery is fat embolism, and not all fat
embolism results in respiratory failure’. Certainly transient post-
operative hypoxaemia is common and there are many possible
causes.
When diagnosed a high proportion of patients need ventilation,
44% in one series.25 In those with X-ray changes and impaired
respiratory function requiring ventilation resolution often occurs
rapidly, on average 3e7 days of invasive support is all that is
required.25,26 There is a continuum of lung injury related to FES from
a group with sub-clinical pulmonary dysfunction at one end to those
who remain ventilator dependent for many days, may be difficult to
oxygenate and are left with long-term pulmonary sequelae.
The rash is the feature closest to being pathognomonic. It is seen
in 33% of cases25 and is frequently axillary but can also be found on
the forehead, sub-mucosa and conjunctiva. The classic distribution
of the rash has been attributed to accumulation of fat droplets in
the aortic arch prior to distribution through carotid and subclavian
vessels to non-dependent areas. Its development may be related to
stasis, endothelial damage by FFA’s or peripheral embolisation but
the exact mechanism is yet to be fully elucidated. Many of these
279
patients will develop a coagulopathy, also a cause of petechiae,
however the rash often occurs with platelet counts above 50,000 at
which level petechiae related to thrombocytopaenia would be
unusual. It is worth remembering that in diagnosing the syndrome
it is the relative platelet count rather than an absolute value that is
important. Coagulopathy, infectious diseases and some congenital
conditions can all result in a similar rash; context is crucial.
Neurologically, patients can present with a wide range of
symptoms and signs from mild confusion and disorientation to
convulsions and coma but neurological dysfunction is common. In
one series of 14 patients, 5 were unconscious, 4 demonstrated
decerebrate posturing and one had a clonic seizure.27
These symptoms may not be present on admission so the
differential diagnosis of unexpected neurological deterioration in
trauma or post-operative orthopaedic patients should include
FES.28e30 This may include a patient with no obvious neurological
problems preeprocedure but a significant deficit afterwards.
Clearly in the trauma patient there are many other potential causes
of delayed neurological deterioration.
It is important to appreciate that some patients have neuro-
logical findings without respiratory dysfunction.14,31 This is
particularly likely if the neurology is focal.32
The outcome from cerebral fat embolism is often, but not
always, good. This is frequently stated in the literature but with
little evidence to support this statement.33 There is no obvious way
of determining prognosis although recently it has been suggested
that MRI could distinguish between reversible vasogenic oedema
and signs of more severe damage, the latter a poor prognostic
indicator.34,35 The more severe cerebral injuries may be associated
with a patent foramen ovale and it has been suggested that pre-
operative closure may prevent embolisation.36
5. Investigations
As a syndrome unsurprisingly there is no single definitive
investigation although MRI may be getting close.
Laboratory tests are often abnormal but there are no specific
tests for FES. Thrombocytopaenia (platelet count <150  109/L) and
anaemia are common (37% and 67%, respectively)25 but are also
features of trauma per se. Biochemistry is unhelpful, hypocalcaemia
and hypoalbminaemia commonly occur in Critical Care patients.
Serum lipase and phospholipase A2 (PLA2) both tend to rise in lung
injury but these changes are not specific to FES. Fat globules may be
identified in both blood and urine but again are non-specific and
may occasionally be seen in normal volunteers.
Bronchoalveolar lavage (BAL) has been used to sample macro-
phages which might be expected to contain fat in FES. Despite
attempts to calibrate the amount of fat in these cells, a lack of
specificity for FES remains a problem.37
Previously a pulmonary artery catheter had been advocated for
the diagnosis of fat embolism by detecting a rise in mean pulmo-
nary arterial blood pressure. However a recent study suggests this
is of no benefit and the majority of patients with confirmed FES
have few if any cardiovascular changes.38 The value of finding fat in
pulmonary arterial blood samples is unknown.39
The chest X-ray usually shows bilateral patchy oedema like
infiltrates. The descriptive term ‘snow storm appearance’ has been
used in more severe cases.
Computer tomography (CT) is generally unhelpful beyond
showing non-specific markers of injury and also for eliminating
other causes of neurological deterioration. One author suggests
that the failure of a neurological picture to correlate with the CT
scan is a reason to consider fat embolism.40 In severe injury it may
show generalised cerebral oedema or high density spots but
usually adds little.
280 P. Sinha et al. / Current Anaesthesia & Critical Care 21 (2010) 277e281
Magnetic resonance imaging (MRI) is showing greater promise.
The term ‘starfield’ describes the pattern seen due to innumerable
punctate areas of restricted diffusion.33 In recent experimental
studies at least two types of changes have been detected in both DWI
(Diffusion Weighted Image) and T2 weighted images within the first
30 min from the insult. Firstly, multiple small non-confluent hyper-
intense lesions are seen in the white and grey matter, which are
thought to be microinfarcts. Secondly, there is a subtle increase in
the signal intensity with isointensity on ADC mapping (apparent
diffusion coefficient) and obvious enhancement with gadolinium.
This represents areas of vasogenic oedema and should be reversible.
They may be due to the presence of free fatty acids and thus may hint
towards a mechanism for some of the pathology. Furthermore the
use of DWI sequences appears useful as both types of lesions were
seen at 7 days but by 21e30 days the vasogenic lesions had dis-
appeared.41 This time line appears to correspond with clinical
improvement.34,42 It is very early days but the MRI changes are
specific enough to support a diagnosis of FES even if they are not yet
pathognomonic. It would seem sensible to perform an MRI in any
patient with orthopaedic injuries who manifests with an acute
alteration in mental status in the presence of a normal CT scan.42
Certainly with the right preconditions and the presence of
adequate criteria, MRI is likely to be very helpful and may be able to
tentatively provide some guarded prognostic information.
6. Prevention of fat embolism
Patients presenting with trauma or for an elective prosthesis
have the highest risk of developing FES but they require different
strategies to try and mitigate that risk.
Primary prevention of trauma is an important aim but by defi-
nition when these patients are admitted the damage has already
been done. We cannot prevent the fat embolus caused by the injury
itself but the management of that injury provides a preventive
opportunity. The most important intervention is early fixation and
ideally this should happen in the first 24 h.43e47 Surgical manipu-
lations in the medullary cavity, in either emergency or elective
work, creates high pressures and predisposes to fat embolism.48
External fixation minimizes interference with the marrow.49 If
the medulla must be invaded then unreamed nails are associated
with a lower incidence of FES than reamed nails,50 sharp reamers
produce less pressure than blunt reamers and hollow nails produce
lower pressure than solid nails.51 Ultrasonic reamers have
a propensity to generate multiple embolic showers.52 There are,
however, some simple surgical measures that can reduce the risk of
FES when performing intra-medullary surgery. This includes
venting medullary cavities to reduce pressure and lavaging the
cavity before inserting any prosthesis.
Corticosteriods have been used as prevention but there are
obvious contraindications in patients following major trauma and
a likely period of critical illness. This is clearly contentious but in the
less critically ill patient’s such as an isolated long bone fracture or
elective joint replacement they may have a role. A recent meta-
analysis in patients with isolated long bone fractures has come
down in favour of using steroids for prevention with a NNT of 8.53
However most of the studies in the meta-analysis have significant
heterogeneity and are over 20 years old, it is debatable whether,
with improvements in surgical technique, the conclusions are still
valid today.
7. Treatment
Good supportive treatment is essential in these patients who
may develop a multitude of problems. This is particularly important
in the management of the respiratory component of the syndrome.
Early diagnosis will not result in any specific intervention
although it may be very useful for informing relatives and in
tempering prognosis. As there is no specific treatment that is of
benefit it is important not to put the patient in jeopardy in order to
clinch the diagnosis. In particular, careful consideration of the risks
of intra-hospital transfer and the support of critically ill patients
undergoing MRI should be weighed up. If necessary the scan should
be delayed until the patient is in a suitable clinical state by which
time they may have recovered what function they are going to
regain, making the MRI less useful.
Steroids pose a problem. The possible benefits must be balanced
against the infective complications especially in patients who are
critically ill. There are case reports of their use54 but both timing and
dosage are ill defined with dosages of 6e90 mg/kg and very variable
treatment durations. In the recent Canadian meta-analysis the
number needed to treat was 8 but it was small (approx. 300 patients)
and it focused only on prevention53 Without further evidence it is
difficult to fully endorse their use. Other drugs such as dextran,
heparin and aspirin are of no proven benefit and have their own
intrinsic problems. Early pre-operative echocardiography and the
closure of any demonstrable PFO may prevent emboli. Unfortunately
there is no magic solution and as usual in ICU it is good supportive care
and avoidance of complications that are the mainstay of therapeutics.
8. Outcome
A syndrome encompasses a wide clinical spectrum. Some
patients do not survive the acute event. Some patients with very
severe lung disease may have residual deficit and may even require
long-term ventilation whilst others may not need any respiratory
support. Similarly the neurological outcome is unpredictable. It is
commonly reported in the literature as a disease process with
a favourable prognosis but this statement is rarely supported by
robust outcome data. MRI appears to move towards definitive
diagnosis, which may be an advance on what was available
a decade ago and may even give us a better idea of prognosis.
Although we may be better at diagnosing the syndrome the only
management continues to be supportive care, this is unlikely to
change until we understand more about its pathophysiology.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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