A fat embolism can travel to most of the organs in the body. Fat embolism and fat embolism syndrome are multiorgan diseases that can damage the kidneys, heart, skin, brain, and lungs. Fat embolism typically manifests at around 24 to 72 hours after the initial insult.

History

The history should elicit the time and onset of symptoms. Also, since most cases of fat embolism and fat embolism syndrome are related to orthopedic trauma, the time and mechanism of the trauma and intraoperative maneuvers should be noted in the history.

Sickle cell disease and other forms of hemoglobinopathy can precipitate fat embolism syndrome. Patients should be asked about the history of sickle cell disease in family members as well as any complications of sickle cell diseases like acute chest syndrome, vaso-occlusive crises, or avascular necrosis of long bones.

History of drug ingestion or alcoholism that can trigger pancreatitis leading to fat embolism syndrome should also be clarified.

The symptoms in fat embolism and fat embolism syndrome are nonspecific. Patients might complain of the following:

• Pain related to bone fracture
• Nausea
• General weakness
• Malaise
• Difficulty breathing
• Headache

Signs and Symptoms

These include but is not limited to the following:

Respiratory

• Tachypnea
• Tachycardia
• Diaphoresis

 Central nervous system

• Agitation from hypoxia
• Restlessness
• Change in mental status
• Seizure
• Coma

Skin

Petechial rash

Eye

Retinal hemorrhage

Physical Examination

Examination of a patient with fat embolism syndrome should be very thorough. Particular attention should be paid to the general appearance of the patient.

General appearance

Most patients with fat embolism syndrome will be anxious, agitated and ill-looking.

Respiratory system 

Assess for the presence of abnormal breath sound, work of breathing, and evidence of respiratory distress or impending respiratory failure.

Cardiovascular

The blood pressure and heart rate might be high in the beginning, but patients might suffer a cardiovascular collapse with ensuing hypotension

Central nervous system 

Glasgow Coma Scale assessment (GCS). A GCS less than 8 is an indication to secure the airway and put the patient on mechanical ventilation. Symptoms involving the central nervous system in fat embolism syndrome is thought to arise from cerebral edema rather than from cerebral ischemia.

Skin 

Usually, the presence of a petechial rash on the skin with all the risk above factors should alert the clinician about fat embolism syndrome.

Eye 

A fundoscopic examination is necessary to check for the presence of retinal hemorrhage.

Diagnosis of fat embolism syndrome can be very challenging because the signs and symptoms can be vague. There are no universally accepted diagnostic criteria. Several authors based on experience and research have proposed diagnostic criteria for fat embolism syndrome.[7][8][9]

Gurd et al. in 1970 and later Wilson in 1974 put forward the following diagnostic criterion requiring two major criteria or at least one major criteria and four minor criteria.

Major Criteria

• Petechial rash
• Respiratory insufficiency
• Cerebral involvement in non-head injury patients

Minor Criteria

• Fever greater than 38.5 C
• Tachycardia heart rate greater than 110 beats per minutes
• Retinal involvement
• Jaundice
• Renal signs
• Anemia
• Thrombocytopenia
• High erythrocyte sedimentation rate
• Fat macroglobulinemia

Schoenfeld  Criteria

Another report by Schoenfeld et al. proposed a quantitative means for the diagnosis of fat embolism syndrome.

A cumulative score greater than five is required for the diagnosis.

• 5 points - petechiae rash 
• 4 points - diffuse infiltrate on x-ray
• 3 points - hypoxemia
• 1 point (for each) - fever, tachycardia, confusion

Lindeque Criteria

Lastly, Lindegue et al. suggested the use of respiratory symptoms alone as the diagnostic criteria for fat embolism syndrome. This criterion has not gained worldwide acceptance when compared to the Gurd, Wilson, and Schoenfeld criteria.

• Sustained Pa02 less than 8 kilopascal 
• Sustained PC02 greater than 7.3 kilopascal
• Sustained respiratory rate greater than 35 breaths per minute despite sedation
• Dyspnea, increased work of breathing, anxiety, tachycardia

Ancillary Studies

Apart from the aforementioned diagnostic criteria, other ancillary studies are needed to aid in the diagnostic workup including the following:

Complete blood count

Anemia and thrombocytopenia are very common in fat embolism syndrome.

Comprehensive metabolic panel

Metabolic acidosis, increased level of BUN, and creatinine can be seen in patients with fat embolism syndrome.

Arterial blood gas

Ventilation-perfusion mismatch is a hallmark of fat embolism syndrome. The arterial blood gas analysis usually has a low partial pressure of oxygen, causing hypoxemia. An increased alveolar-arterial (A-a) gradient is common in fat embolism syndrome. The A-a gradient is the difference in the partial pressure of oxygen in the alveolus and the partial pressure of oxygen in the pulmonary artery. In fat embolism syndrome, there is occlusion of the pulmonary blood vessels, causing impairment of perfusion with normal ventilation. The end result of this in fat embolism syndrome is a ventilation-perfusion mismatch.

To calculate the A-a gradient, use the formula:

A-a gradient = PA02 - Pa02

• Pa02 is the partial pressure of oxygen in the pulmonary artery
• PA02 is the partial pressure of oxygen in the alveolar sac

To calculate the PAO2 and Pa02 

• PAO2 = FiO2 (P atmospheric - P water vapor) – (PCO2/R).
• PaO2 = partial pressure of oxygen in the pulmonary artery.

PaO2 in arterial blood gas can be used as follows.

• FiO2 is the concentration of inspired oxygen expressed as a fraction.

This is around 0.21 at room air.

• P atmospheric is the barometric pressure (760 mmHg at sea level).
• P water vapor is the water vapor pressure (48 mmHg at 37 C).
• PaCO2 is the partial pressure of alveolar carbon dioxide.

If approximated, this is presumed to be equal to arterial PCO2. PACO2 is presumed to be equal to 40 mmHg

• R is the respiratory quotient and is equated to about 0.8 on a regular diet.

The normal alveolar partial pressure of oxygen is as follows: 

• PA02 = alveolar partial pressure of O2 = FiO2 × (patmospheric - P water vapor) - (PCO2/R).
• 0.21 × (760 - 48) - (40/0.8) = 150-50 = 100 mmHg

The normal partial pressure of oxygen in arterial blood is beween 75 to 100mmHg.

• PA02 - Pa02 = 100 mmHg - 75 mm = 25 mmHg
• PA02-Pa02 =100 mmHg -100 mmHg = 0 mmHg

This implies that the A-a gradient can have values that range from 0 to 25 mmHg

The normal A-a gradient is usually less than 10 mmHg. This can increased significantly in fat embolism syndrome because of ventilation-perfusion mismatch.

Bronchoalveolar Lavage

Bronchoalveolar Lavage (BAL) has been researching extensively as a diagnostic tool for fat embolism syndrome. Lipid inclusion in the macrophages might point to a diagnosis of fat embolism syndrome but is not specific, as this can be seen in other clinical conditions. Moreover, the procedure is time-consuming, invasive, and might not give the best diagnostic yield.

Attempts at developing biological markers for fat embolism syndrome have been disappointing because of low specificity. Lipase, free fatty acid, and phospholipase A2 have been demonstrated to be elevated in fat embolism syndrome, but this also can be seen in other disease conditions of the lung

Blood, urine, and sputum analysis might show the presence of fat globules. Again, this is nonspecific in fat embolism and fat embolism syndrome.

Imaging Studies

Chest x-ray

The chest X-ray will reveal the presence of the following:

• Diffuse interstitial marking
• Pulmonary edema
• Lung infiltrate
• Flake-like pulmonary marking (snowstorm appearance)31

CAT scan of the chest

• Area of  increased vascular congestion
• Pulmonary edema

Imaging of the brain

CAT scan

This is not a very sensitive imaging study of the brain in fat embolism syndrome, but it can be used to exclude other causes of altered mental status such as epidural, subdural or subarachnoid bleed.

MRI

This is the most sensitive test that can be used to demonstrated changes in the brain related to fat embolism syndrome. Takahashi et al. categorized these changes into the following four grades based on the size and distribution of the lesions in T2 weighted imaging:

• Grade 0 - normal
• Grade 1 - mild
• Grade 2 - moderate
• Grade 3 - severe

Lesions seen in fat embolism syndrome are distributed in the following areas of the brain:

• Centrum semi vale,
• Subcortical white matter
• Ganglionic regions
• Thalamus

The authors demonstrated that resolution of these lesions correlates well with clinical recovery from fat embolism syndrome. Some of these lesions develop as a result of vasogenic edema from free fatty acids (FFA) which is potentially neurotoxic.

Transesophageal echocardiography may be utilized intraoperatively to monitor the release of fat globules or bone marrow materials into the bloodstream during the process of intramedullary nailing and reaming. Fat emboli in the pulmonary artery can increase the pulmonary artery wedge pressure as well as the right ventricular afterload.

Pharmacotherapy

There is no specific treatment for fat embolism or fat embolism syndrome. Based on experimental studies, an attempt was made to use dextrose infusion to decrease FFA mobilization. Ethanol also was used as an agent to inhibit lipolysis. In clinical practice, there were no proven benefits.[10][11][12]

Experimental use of heparin in an animal model was found to be beneficial but is no longer used in clinical practice because of the potential risk of bleeding. There has not been a proven clinical benefit with the use of heparin in fat embolism syndrome.

Therapy with corticosteroids has been proposed for the treatment of fat embolism syndrome based on the following effects of corticosteroids:

• Inhibition of complement activated leucocyte aggregation
• Limiting FFA level
• Membrane stabilization

A meta-analysis of seven randomized control trials using corticosteroid prophylaxis showed close to 77% reduction in the risk for fat embolism syndrome in a patient with a long bone fracture. There is, however, no difference in mortality, infection, or avascular necrosis between the treatment group and control. For this reason, the use of corticosteroids is still very controversial.

Inferior Vena Cava Filter

This has been proposed as a measure to prevent the showering of fat emboli. As a prophylactic treatment for fat embolism syndrome, placement of an inferior vena cava filter has not been studied sufficiently.

Operative Measures

It is highly recommended to start early open reduction and internal fixation of long bone fractures. The incidence of fat embolism syndrome is higher in a patient with long bone fractures who are managed conservatively.

The use of internal fixation devices in the management of fractures of long bones significantly reduces the incidence of fat embolism syndrome.

During operative fixation of the long bone fracture, care must be taken to limit the intramedullary pressure, as a high pressure is associated with an increased amount of fat emboli entering the systemic circulation.

Some techniques utilized in orthopedic surgery to reduce embolization include:

• Lavage of bone marrow prior to fixation
• Venting of the femoral bone
• Drilling of small holes in the cortex of the bone to lower intramedullary pressure

None of these maneuvers has been shown to reduce fat embolism syndrome.

Supportive Care

This is the mainstay treatment once a patient develops fat embolism syndrome. Supportive care is geared towards adequately oxygenating the end organs.

Goals of Supportive Care

• Provision of adequate oxygenation and ventilation
• Maintenance of adequate hemodynamic stability
• Transfusion of packed red blood cells to improve oxygen delivery if indicated
• Prophylaxis of deep venous thrombosis with a sequential compression device
• Adequate nutrition and hydration

Supplemental oxygen might be required, and if the patient develops fulminant acute respiratory distress syndrome, intubation and mechanical ventilation might be required.

Albumin

Albumin is recommended as part of the resuscitation tools for hypovolemia. It restores intravascular volume and helps to bind free fatty acid. This prevents the systemic dissemination of fat globules.

Indications for Intubation

• Altered mental status with Glasgow coma score of less than 8
• Moderate to several respiratory distresses with no improvement on noninvasive support

fat embolism syndrome might also cause pulmonary hypertension with right ventricular failure. Inotropic support with dobutamine or a phosphodiesterase inhibitor like milrinone might be required.

Cerebral edema if present might require management with the following:

• Mannitol
• Hypertonic saline
• Intracranial pressure monitors

The differential diagnosis of fat embolism and fat embolism syndrome are related to each system that this system disease affects

Respiratory

fat embolism syndrome and fat embolism should be distinguished from

• Pulmonary Contusion
• Pulmonary edema
• Aspiration pneumonia
• Pulmonary Thromboembolism.

CT of the chest can aid in distinguishing fat embolism syndrome from other pathologies of the lung.   

Pulmonary contusion – Typically develops after about 6 to 10 hours of a chest injury, on CT of the chest, there is a localized ground glass opacification on the lung.

Pulmonary edema – In pulmonary edema, there is symmetrical vascular engorgement with pleural effusion and ground-glass opacification.

Thromboembolism – The gold standard for diagnosis is CT angiogram of the chest where classically a filling defect will be present.

Central Nervous System

Clinical conditions affecting the central nervous system that should be factored in the differential diagnosis:

• Meningitis
• Encephalitis
• Brain tumor
• Epidural
• Subdural
• Subarachnoid bleed

All the conditions listed above can cause altered mental status with a change in Glasgow Coma Scale mimicking fat embolism syndrome. CAT scan of the brain can help delineate a bleed or tumor. Meningitis and encephalitis can be ruled out with a lumbar puncture and cerebrospinal fluid analysis

Skin Rash

The following conditions can present with petechial skin rashes

• Idiopathic thrombocytopenic purpura,
• Thrombotic thrombocytopenic purpura,
• Leukemia

All of these blood disorders should be considered in the presence of skin rash and other associated clinical signs and symptoms. Consultation with a hematologist/oncologist and dermatologist can help in the clinical diagnosis.

In patients with traumatic fat embolism syndrome, the prognosis depends on early open reduction and internal fixation of the long bone fracture. Most patients with adequate support therapy can recover from the neurological, respiratory, and retinal changes associated with fat embolism syndrome. The most recent studies approximate mortality between 7% to 10%.

The most common cause of morbidity or mortality include:

• Acute respiratory distress syndrome ARDS
• Cerebral edema

The diagnosis and management of fat embolism is best done by an interprofessional team. The diagnosis is not always simple and there is no specific treatment for the disorder. The key is to keep the patient hydrated and ensure that the fractured limb is immobilized or fixed promptly. Many agents have been recommended for the treatment of fat embolism but none has proven to be reliable or consistently effective.

A meta-analysis of seven randomized control trials using corticosteroid prophylaxis showed close to 77% reduction in the risk for fat embolism syndrome in a patient with a long bone fracture. There is, however, no difference in mortality, infection, or avascular necrosis between the treatment group and control. For this reason, the use of corticosteroids is still very controversial.

The prognosis of patients with fat embolism depends on early open reduction and internal fixation of the long bone fracture. Most patients with adequate support therapy can recover from the neurological, respiratory, and retinal changes associated with fat embolism syndrome. Delays in treatment can lead to ARDs, cerebral edema and a mortality rate that averages 7%. [13][14](Level V)