Medscape knowledge converted to a presentation

1. FAT EMBOLISM
A topic presentation at Amala Institute of Medical Sciences
by
Dr. Libin Thomas Manathara

2. Background
• For those who manage major trauma victims, the topic of fat
embolism weighs heavily on the mind
• The incidence of this problem can approach 90% in patients who have
sustained major injuries
• If it progresses to the rare clinical entity known as fat embolism
syndrome (FES), a systemic inflammatory cascade affecting multiple
organ systems, morbidity and mortality are high
• Accordingly, swift diagnosis and treatment of fat embolism are
paramount for ensuring the survival of this patient population

3. Background
• Ernst Von Bergmann, in 1873, was the first person credited with
making a clinical diagnosis of fat embolism
• He did this on the basis of knowledge gathered from experiments
with cats 10 years previously, in which he injected them with
intravenous oils
• Von Bergmann later described a patient who fell off a roof and
sustained a comminuted fracture of the distal femur; 60 hours after
the injury, the patient developed dyspnea, cyanosis, and coma

4. Background
• The diagnosis of FES is mainly a clinical one
• It is dependent on clinical identification of dyspnea, petechiae, and
cognitive dysfunction in the first few days following trauma, long
bone fracture, or intramedullary surgery
• Various laboratory studies and imaging modalities exist to aid in its
discovery
• Supportive measures are the mainstay of treatment; thus, efforts are
targeted at prevention, early diagnosis, and symptom management

5. Pathophysiology
• The exact mechanism of fat embolism and its evolution to the entity
known as FES has not been fully elucidated, but a number of
experimental models have been proposed
• Asymptomatic fat embolism to the pulmonary circulation almost
always occurs with major trauma, including elective surgical
procedures such as intramedullary nailing of long bones, which has
been demonstrated with echocardiography
• The development of FES is rare, occurring in 0.5-11% of cases

6. Pathophysiology
• Although poorly understood, the development of FES is attributed to
a series of biochemical cascades resulting from the mechanical insult
sustained in major trauma
• Release of fat emboli leads to occlusion of the microvasculature,
triggering an inflammatory response that is clinically manifested by
dermatologic, pulmonary, and neurologic dysfunction

7. Frozen section of lung stained with oil red O showing multiple orange red fat globules of varying sizes in septal
vasculature.

8. Hematoxylin-eosin stain of section of lungs showing blood vessel with fibrinoid material and optical empty space
indicative of presence of lipid dissolved during staining process. This 55-year-old woman died of massive fat
embolism after developing pancreatitis due to endoscopic retrograde cholangiopancreatography.

9. Pathophysiology
• Pulmonary consequences of FES are clinically similar to those of acute
respiratory distress syndrome (ARDS) and almost always occur
• They are usually the initial manifestation of FES, typically appearing
within 24 hours after the traumatic insult
• They result from injury to the pulmonary capillary endothelium
caused by free fatty acids that were hydrolyzed by lipoprotein lipase,
releasing local toxic mediators
• These mediators cause increased vascular permeability, resulting in
alveolar hemorrhage and edema and causing respiratory failure and
ARDS

10. Pathophysiology
• Approximately 20-30% of the population have a patent foramen
ovale; this may explain how fat emboli that pass through the
pulmonary circulation end up with systemic manifestations of FES,
particularly involving the brain and kidneys
• As a result of the occluded cerebral vasculature, patients exhibit gross
encephalopathy, localized cerebral edema, and white-matter changes

11. Etiology
• Blunt trauma (associated with 90% of all cases)
• Acute pancreatitis
• Diabetes mellitus
• Burns
• Joint reconstruction
• Liposuction
• Cardiopulmonary bypass
• Decompression sickness
• Parenteral lipid infusion
• Sickle cell crisis
• Pathologic fractures

12. History
• Major blunt trauma, usually resulting in long-bone fractures, pelvic
fractures, or both
• Elective long-bone orthopedic procedures or cardiothoracic
procedures
• Parenteral lipid infusion
• Recent corticosteroid administration

13. Physical Examination
• Gurd and Wilson have outlined an approach to diagnosing fat embolism
syndrome (FES) on the basis of major and minor criteria
• One major criterion, four minor criteria, and the presence of macroglobulinemia
are required for the diagnosis

14. Major criteria for diagnosing FES
• Symptoms and radiologic evidence of respiratory insufficiency
• Cerebral sequelae unrelated to head injury or other conditions
• Petechial rash

15. Minor criteria
• Tachycardia (heart rate >110 beats/min)
• Pyrexia (temperature >38.5° C)
• Retinal changes of fat or petechiae
• Renal dysfunction
• Jaundice
• Acute drop in hemoglobin level
• Sudden thrombocytopenia
• Elevated erythrocyte sedimentation rate
• Fat microglobulinemia

16. Physical Examination
• Early signs of the systemic inflammatory response syndrome (SIRS)
may herald the onset of FES
• Tachypnea, dyspnea, and hypoxia appear as a result of ventilation-
perfusion abnormalities 12-72 hours after injury
• Alert clinicians may notice reddish-brown nonpalpable petechiae
developing over the upper body, particularly in the axillae, within 24-
36 hours of insult or injury

17. Physical Examination
• These petechiae occur in 20-50% of patients and resolve quickly, but
they are virtually diagnostic in the right clinical setting
• Subconjunctival and oral hemorrhages and petechiae can also appear
• Central nervous system dysfunction initially manifests as agitation or
delirium but may progress to stupor, seizures, or coma and is
frequently unresponsive to correction of hypoxia
• Retinal hemorrhages with intra-arterial fat globules are visible upon
funduscopic examination

18. Diagnostic Considerations
• Every effort should be made to look for treatable or life-threatening
disorders before the diagnosis of fat embolism syndrome (FES) is
made
• Computed tomography (CT) of the head is necessary to rule out
intracranial pathology
• A careful search for infectious agents and possibly the institution of
empiric antibiotics are necessary until an infectious source is ruled
out

19. Differential Diagnoses
• Pulmonary Embolism
• Thrombotic Thrombocytopenic Purpura (TTP)

20. Workup- Laboratory Studies
• An otherwise unexplained increase in pulmonary shunt fraction alveolar-to-
arterial oxygen tension difference, especially if it occurs within 24-48 hours of a
sentinel event associated with fat embolism syndrome (FES), is strongly
suggestive of the syndrome
• Thrombocytopenia, anemia, and hypofibrinogenemia are indicative of FES;
however, they are nonspecific
• Urinary fat stains are not considered to be sensitive or specific enough for
diagnosing FES or for determining the risk of it
• Fat globules in the urine are common after trauma

21. Workup- Laboratory Studies
• Preliminary investigations of the cytology of pulmonary capillary
blood obtained from a wedged pulmonary artery catheter revealed
fat globules in patients with FES and showed that this method may be
beneficial in early detection of patients at risk
• In the future, genotyping for polymorphisms associated with
increased susceptibility to inflammatory stimuli may help identify
those at risk for FES
• Specific antibody therapy targeting inflammatory molecules has not
been useful

22. Radiography and Computed Tomography
• Serial chest radiographs reveal increasing diffuse bilateral pulmonary infiltrates
within 24-48 hours of the onset of clinical findings
• Findings from noncontrast computed tomography (CT) of the head performed
because of alterations in mental status may be normal or may reveal diffuse
white-matter petechial hemorrhages consistent with microvascular injury
• Because the embolic particles are lodged in the capillary beds, helical CT findings
may be normal
• Parenchymal changes consistent with lung contusion, acute lung injury, or acute
respiratory distress syndrome (ARDS) may be evident
• Nodular or ground-glass opacities in the setting of trauma suggest fat embolism

23. Ultrasonography
• In a small case study, five patients with trauma were monitored with
intracranial Doppler ultrasonography, two during intraoperative
nailing of long-bone fractures
• Cerebral microembolic signals were detected as long as 4 days after
injury
• Transesophageal echocardiography (TEE) may be of use in evaluating
the intraoperative release of marrow contents into the bloodstream
during intramedullary reaming and nailing

24. Ultrasonography
• The density of the echogenic material passing through the right side
of the heart correlates with the degree of reduction in arterial oxygen
saturation
• Repeated showers of emboli on TEE have been noted to increase right
heart and pulmonary artery pressures
• Embolization of marrow contents through a patent foramen ovale
also has been noted
• However, evidence of embolization obtained by means of TEE is not
correlated with the actual development of FES

25. Bronchoalveolar Lavage With Staining for Fat
• Bronchoalveolar lavage (BAL) specimens have been evaluated in
trauma patients and sickle-cell patients with acute chest syndrome,
and the results have been mixed
• Lipid inclusions commonly appear in patients with traumatic and
nontraumatic respiratory failure; the standard cutoff in the BAL
studies—5% fat-containing macrophages—results in a low specificity
for the test
• To improve specificity, some authors suggest raising the cutoff to 30%
• At present, using BAL to aid in the diagnosis of FES or to predict its
likelihood is controversial

26. Other Studies
• Scant data exist regarding magnetic resonance imaging (MRI) findings
in patients with FES; however, in one small patient group, multiple
nonconfluent, hyperintense lesions were seen on proton-density–
and T2-weighted images
• Nuclear ventilation-perfusion imaging of the lungs may be performed
when pulmonary embolism is suspected
• The findings from this scan may be normal or may demonstrate
subsegmental perfusion defects

27. Supportive Medical Care
• Specific medical therapy for fat embolism and fat embolism syndrome (FES) does
not exist at this time, and supportive measures have not been tested in adequate
randomized, controlled trials
• Treatments such as heparin, dextran, and steroids have not been shown to help
reduce morbidity and mortality, but methylprednisolone given prophylactically
may have beneficial effects

28. Supportive Medical Care
• Current care of patients with fat embolism is aimed at supporting physiologic
derangements and includes the following:
• Maintenance of adequate oxygenation and ventilation with open lung strategies such as the
use of airway pressure release ventilation (APRV)
• Maintenance of hemodynamic stability
• Administration of blood products as clinically indicated
• Hydration
• Prophylaxis of deep venous thrombosis and stress-related gastrointestinal bleeding
• Nutrition

29. Supportive Medical Care
• Judicious use of crystalloids, colloids, and diuretics is necessary; volume depletion
may precipitate shock and organ dysfunction, but volume overload may worsen
the hypoxia
• Continuous pulse oximetry monitoring in at-risk patients (eg, patients with long-
bone fractures and multiple trauma), may facilitate early detection of
desaturation, allowing prophylactic administration of oxygen and possibly
steroids, thereby decreasing the chances of hypoxic injury and systemic
complications of FES
• At-risk patients should be placed in a monitored setting, and appropriate services
should be consulted
• If a patient has sustained major traumatic injuries, transfer to the nearest trauma
center with 24-hour in-house surgical intensive care is essential

30. Surgical Management
• Early stabilization of long bone fractures is recommended to minimize bone
marrow embolization into the venous system
• Rigid fixation within 24 hours has been shown to yield a fivefold reduction in the
incidence of FES
• Appropriate surgical technique, particularly in reaming or nailing the marrow,
may help reduce the volume of fat embolization
• Utilization of a vacuum or venting during reaming has been shown to decrease
the incidence of fat embolization
• Prophylactic placement of inferior vena cava filters may help reduce the volume
of fat that reaches the heart in at-risk patients

31. Prevention
• Several studies performed in the late 1970s attempted to show that use of
methylprednisolone as a “membrane stabilizer” would reduce the incidence of
FES, but follow-up work has yet to reproduce these findings
• A meta-analysis of randomized trials studying corticosteroid use as a preventive
adjunct in patients with long-bone fractures uncovered 104 studies, of which only
seven met the authors' eligibility criteria for analysis
• Although the pooled analysis of 389 patients found that corticosteroids reduced
the risk of FES by 78%, the authors warned that these studies were of poor
quality and held to standards of the 1970s

32. Prevention
• The use of heparin has been shown to reduce the degree of
pulmonary comprise and intravascular coagulation despite the risk of
hemorrhage and intravascular lipolysis; however, this practice has not
been shown to yield a statistically significant benefit
• Ethanol (which decreases lipolysis) and dextrose (which decreases
free fatty acid mobilization) have been used as prevention modalities,
but at present, there is little to no evidence to support the use of
these agents in FES

33. Medication Summary
• The goals of pharmacotherapy for fat embolism syndrome (FES) are to reduce
morbidity and prevent complications
• Corticosteroids may be used in certain cases
• The best dosing protocol for corticosteroids in the prophylaxis of FES has not
been established, and currently, there is no treatment regimen

34. Corticosteroids
• Corticosteroids have anti-inflammatory properties and cause
profound and varied metabolic effects
• They modify the body’s immune response to diverse stimuli

35. Methylprednisolone (Depo-Medrol, Medrol,
Solu-Medrol, A-Methapred)
• Methylprednisolone is most often used for the prophylaxis of FES in
at-risk patients
• Currently, there are no good data to support the use of this agent
over the use of any other steroids

36. Isotonic Crystalloids
• Isotonic sodium chloride solution (normal saline [NS]) and lactated
Ringer (LR) solution are isotonic crystalloids, the standard intravenous
(IV) fluids used for initial volume resuscitation
• They expand the intravascular and interstitial fluid spaces
• Typically, about 30% of administered isotonic fluid stays intravascular;
therefore, large quantities may be required to maintain adequate
circulating volume

37. Isotonic Crystalloids
• Both fluids are isotonic, and they have equivalent volume-restorative
properties
• Whereas some differences exist between the metabolic changes
observed with the administration of large quantities of one fluid and
those observed with high-volume administration of the other, for
practical purposes and in most situations, these differences are
clinically irrelevant
• No demonstrable difference in hemodynamic effect, morbidity, or
mortality exists between resuscitation with NS and resuscitation with
LR solution

38. Normal saline (NS, 0.9% NaCl)
• NS restores interstitial and intravascular volume
• It is used in initial volume resuscitation

39. Lactated Ringer
• RL solution restores interstitial and intravascular volume
• It is used in initial volume resuscitation

40. Colloids
• Colloids are used to provide oncotic expansion of plasma volume
• They expand plasma volume to a greater degree than isotonic crystalloids and
reduce the tendency of pulmonary and cerebral edema
• About 50% of the administered colloid stays intravascular

41. Albumin (Buminate, Albuminar-5, Albuminar-
25, Plasbumin-5, Plasbumin-25)
• Albumin has been recommended for volume resuscitation
• It is useful for plasma volume expansion and maintenance of cardiac
output
• It also binds with the fatty acids and may thus decrease the extent of
lung injury
• Five-percent solutions are indicated to expand plasma volume,
whereas 25% solutions are indicated to raise oncotic pressure

42. THANK YOU