Which findings would be present in a client who has fat embolism syndrome?

Fat embolism

Fat embolism is a rare entity, but occurs most commonly as a result of long bone fractures and polytrauma. It may be related to excessive pseudomotion of unstable fracture or internal fixation with IM nail. It is most common in young males aged 10–40 years and is rare in children and the elderly. This may be related to the low fat content of bone marrow in children and the minimal trauma fractures that tend to occur in the elderly.66

Two theories regarding the pathophysiologic mechanism of fat embolism syndrome (FES) exist – the mechanical hypothesis and the biochemical hypothesis. The mechanical hypothesis postulates that an increase in IM pressure forces marrow particles, fat, or bone fragments into the circulation via the open venous sinusoids. This leads to obstruction of peripheral and lung microcirculation. This results in ventilation–perfusion mismatch, low partial pressure of oxygen, and low oxygen saturation. Cerebral and renal embolization may contribute to the symptoms. The biochemical hypothesis postulates that physiochemical alteration occurs when fat globules are acted upon by lipoprotein lipase, resulting in the release of free fatty acids. This results in the release of toxic intermediates that can cause direct injury to pneumocytes and lung endothelial cells.67

FES is characterized by progressive respiratory insufficiency, deteriorating mental status, and petechial rash (major diagnostic criteria). Minor diagnostic criteria include pyrexia, tachycardia, retinal changes, jaundice, oliguria/anuria, thrombocytopenia, high erythrocyte sedimentation rate, and fat macroglobulinemia. According to Gurd and Wilson, the diagnosis of FES involves two major criteria, or one major plus four minor criteria plus fat microglobulinemia.68 Typically, FES occurs within 24–72 h after injury and is largely a clinical diagnosis. Laboratory investigations may include an arterial blood gas to diagnose hypoxemia and cytologic examination of urine, blood, or sputum looking for fat globules. Chest radiography may be normal in these patients, prompting investigation with chest CT or bronchoalveolar lavage looking for fat-laden macrophages.69 Because of the lack of specific diagnostic criteria or investigations, the incidence of FES is likely to be underestimated.

Once FES is suspected, the management is largely supportive and usually involves management of the hypoxemia. Prophylactic measures in those considered at risk for FES are most important. These include early stabilization of long bone/pelvic fractures, minimizing IM pressures during reaming, and irrigation of marrow prior to insertion of prostheses. Pharmacologic therapies have been disappointing and, despite initial interest in using steroids, there have not been any level 1 studies supporting their use.

Fat embolism syndrome

Fat embolism syndrome (FES) was first described in 1861 by Zeuker.81 FES can be a complication of fractures of long bones, such as the femur, and is associated with various neurologic signs including paralysis, tremor, delirium, stupor, and coma. FES has been diagnosed in 5% of all patients with fractures. Clinical features usually commence between 24 and 48 hours after the injury, and the mortality rate has been reported to be as high as 30%.82 It was suggested that FES is caused by the delayed release of fat droplets from pulmonary fat emboli, by repeated influx of emboli from an inadequately fixed fracture, or by fatty acid hydrolyzed from neutral fat. The pathologic changes in FES are produced by combined mechanical damage induced by fat droplets and biochemical damage induced by fatty acids.82

Retinopathy has been reported in 50% of patients with FES and in 4% of patients with long-bone fractures presenting with a subclinical syndrome. Typical lesions consist of cotton-wool spots and flame-like hemorrhages, and are attributed to microvascular injury and microinfarction of the retina. Retinal lesions disappear after a few weeks, although scotomas may persist.83

Fat Embolism Syndrome

Fat embolism syndrome (FES) is a poorly understood complication of skeletal trauma. Although rare, FES most often occurs after fractures of long bones or other conditions resulting in bone marrow disruption. FES is characterized by the appearance of free fat and fatty acids in the blood, lungs, brain, kidneys, and other organs. The classic triad of respiratory insufficiency, neurologic abnormalities, and petechial rash occurs in 0.5% to 2.0% of solitary long bone fractures. The incidence increases to 5% to 10% in multiple fractures with pelvic involvement.

FES is a clinical diagnosis that typically manifests within 12 to 72 hours of initial injury. Respiratory impairment leads to hypoxemia in up to 30% of patients and, on occasion, to respiratory failure and the need for mechanical ventilation. The chest radiograph often shows diffuse infiltrates but can appear normal. Cerebral symptoms may occur in 60% of patients and tend to follow the pulmonary symptoms. Neurologic findings may range from restlessness, confusion, and altered sensorium to focal deficits, seizures, and coma. The characteristic petechial rash is observed in 50% of patients and usually is found on the neck, in the axillary region, or on the trunk, or petechiae may appear on the conjunctiva. The rash often is the last of the triad to develop and resolves within a range of hours to days.

Treatment of FES includes aggressive supportive care and early ventilatory support. Steroids have been demonstrated to be efficacious as prophylaxis for FES, although experience with steroids as specific treatment remains anecdotal.

Fat Embolism

Fat embolism is a syndrome associated with long bone fractures in which fat emboli to the lungs lead to respiratory problems. It is believed to be caused by dissolution of normal circulating fat; however, the exact mechanism is still unexplained.64,71 This condition may be due to actual leaking of fat into the bloodstream or a metabolic change that allows normal circulating fat to become free fatty acids.71 Mudd and associates68 examined patients who died of fat embolism syndrome after blunt trauma. They found no particular source of the fat, nor was evidence of bone marrow or myeloid tissue seen in the lung sections. Many children have fat emboli after injury, but the clinical syndrome develops in very few.58,78 Fabian and colleagues62 found the an incidence of fat emboli in pediatric and adolescent long bone fractures to be as high as 10%. Fat embolism is more often seen in teenagers and late adolescents, and the onset is usually shortly after the injury (within the first 2 to 3 days). Mudd and colleagues found no correlation with the number or severity of fractures; rather, fat embolism syndrome was more likely to be related to the extensive nature of the soft tissue injuries. The pulmonary changes prevent exchange of oxygen across the alveolar–capillary membrane. In adults, this condition is referred to as adult respiratory distress syndrome. The incidence of fat embolism syndrome is markedly decreased by immediate internal stabilization of long bone fractures as opposed to treatment by traction or late reduction.65,69–71 Intramedullary fixation of long bones (particularly diaphyseal fractures of the femur) is preferred because it reduces the risk of fat embolism syndrome. However, reaming for the nail can cause an increase in circulation and can potentially increase the risk of a fat embolism to the lung.63 Fat embolism syndrome has been reported in children with muscular dystrophy and as a complication of closed femoral shortening.61 Patients who are at risk of developing fat embolism syndrome should be monitored with pulse oximetry.61

With the full-blown syndrome, children have respiratory distress, tachypnea, and a deterioration in blood gas values, particularly O2 saturation.58 Clinically, the child may appear restless and confused; if untreated, stupor and coma may ensue. Petechiae may develop on the skin of the chest, axilla, and base of the neck, but they may be transient and are frequently missed.64 The most significant laboratory finding is a decrease in arterial oxygen tension. Examination for fat in urine and sputum is of little value relative to more modern diagnostic measures. Recently, bronchoalveolar lavage for detection of fat-containing cells and retinal examination for cotton-wool spots and retinal hemorrhages have been reported to be helpful in early diagnosis.59,60 A chest radiograph classically demonstrates interstitial edema and increased peripheral vascular markings.64

If untreated, fat embolism can be lethal; however, early diagnosis and prompt management can usually sustain the patient until the problem clears. Treatment consists of supportive measures for the respiratory problem, including improvement in oxygen saturation (70 mm Hg), and may require endotracheal positive-pressure breathing. The blood volume should be restored, and fluid and electrolyte balance should be maintained. Adequate oxygenation is the most important part of treatment because respiratory failure is the most common cause of death. Treatment with steroids and heparin remains controversial.

Fat Embolism

Fat embolism occurs most often after serious physical trauma that causes bone fractures. The frequency, clinical and laboratory features, and circumstances of the fat embolism syndrome have been extensively described.3,353–357 The syndrome consists of a triad of respiratory distress, decreased alertness, and a petechial rash developing 24 to 48 hours after an injury. Table 9-6 lists the major findings in patients with the fat embolism syndrome. Fat embolism is most often found after blunt physical trauma with fractured bones but can occur after cardiac surgery and in patients who have bone infarctions. In patients with injuries, the long bones and pelvis are most often involved especially the femurs. The fat embolism syndrome is unusual in children and in patients with fractures limited to the upper extremities.353 Often the cause is multiple fractures resulting from vehicular accidents. Investigators retrospectively reviewed 10 years of experience of the fat embolism syndrome found at one trauma center and found 27 instances among 3026 patients (0.9%) with long-bone fractures.354

Occasionally the fat embolism syndrome develops after cardiac surgery when the atria or ventricles are entered.358,359 The mechanism of fat embolism after open heart surgery is unclear, but fat from the sternotomy or epicardial fat may directly enter the systemic circulation. Cardiotomy suction tubes draining the pericardium during cardiopulmonary bypass contain variable quantities of fat globules.

Fat embolism has also been reported in patients with sickle cell anemia (homozygous S-S and those who have S-C disease).360–363 In sickle-cell-disease patients, the fat originates from bone and bone marrow infarcts. Bone and joint pain and crisis may precede fat embolism in some patients.

Fat embolism has also been described after therapeutic procedures that use lipid substances to form stable drugs for injection. Lipidol has been used to mix with anticancer drugs that are fat soluble to form stable covalent conjugates. This mixture is then injected into an artery feeding a tumor, such as in the liver. Fat embolism has been described after such therapeutic procedures.364 The clinical findings included dyspnea and decreased alertness. Hypoxemia preceded or accompanied stupor. MRI showed multiple focal abnormalities mostly in border-zone regions. The neurologic signs were severe but transient and cleared completely within weeks. None of the three reported patients had cardiac shunts demonstrable by echocardiography.364 Fat emboli can occasionally be introduced during placement of pumps designed to release pharmaceutical agents into the cerebrospinal fluid.365 Parenteral nutrition containing high lipid content occasionally is infused into a cervicocranial artery when a catheter is misplaced into an artery rather than a vein.

The fat embolism syndrome usually develops after a delay of a few hours up to a few days after trauma. In one series of 14 patients, all of whom had traumatic injuries with long bone fractures, the latency of onset of signs of fat embolism after trauma ranged from 12 to 72 hours (mean 41 hours).356 At times the clinical manifestations of fat embolism can be delayed for as long as 5 days.357 Most patients have symptom onset between 24 and 72 hours after injury.

The major clinical manifestations of the fat embolism syndrome are dyspnea, tachypnea, fever, tachycardia, petechiae, and neurologic dysfunction.1 Jaundice can also occur. Neurologic symptoms and signs may precede or follow respiratory distress and are characterized as confusion with delirium often followed by a decrease in the level of consciousness. Neurologic symptoms and signs are present in more than 80% of patients. Most often patients develop an encephalopathy characterized by restlessness, agitation, confusion, poor memory, and decreased alertness. This state often passes into stupor or coma. Seizures are common at onset or early during the course of illness. Seizures can be focal or generalized. Focal neurologic signs are also common and include hemiparesis, conjugate eye deviation, aphasia and visual field abnormalities. Motor abnormalities including increased tone in the lower extremities, Babinski signs, and decerebrate rigidity are often found. Focal neurologic signs were noted in 33% of patients in one series.357 Some patients have scotomas and other visual abnormalities related to retinal dysfunction caused by fat embolism.

Pulmonary symptoms develop shortly after or concurrent with the neurologic symptoms. Dyspnea and tachypnea are prominent and patients may become cyanotic. Tachycardia, high fever, and circulatory collapse also occur; hypotension is often related to blood loss, hypoxemia, and hypovolemia. Renal failure can develop. The pulmonary emboli can result in increased resistance in the pulmonary artery bed and increased pressures in the right side of the heart. In patients with a PFO, pulmonary hypertension may promote extensive right-to-left passage of fat emboli through the PFO.

An important clue to the presence of fat microemboli is the presence on physical examination of petechiae. Petechiae are found in 50% to 75% of patients with the fat embolism syndrome. They are most often found in the lower palpebral conjunctivae and the skin of the neck, shoulder, and the axillary folds.1,353,354 Another important clinical clue is the appearance of fat emboli within the arteries of the eye. Microinfarcts are sometimes visible in the optic fundus especially in the perimacular regions. Small hemorrhages sometimes with white pale centers are also found. Fat globules can sometimes be seen within retinal arteries. Papilledema is occasionally found.

Laboratory tests are often helpful in diagnosis. Many patients develop abnormal chest x-rays. Fine stippling and fluffy lung infiltrates are common and are seen diffusely through the lung fields. Most patients have a drop in hemoglobin and hematocrit due to traumatic loss of blood and hemolysis. Thrombocytopenia and prolonged prothrombin and activated partial thromboplastin times are common, and are attributed to a consumptive coagulopathy. Frank disseminated intravascular coagulation may also occur. TCD monitoring of patients with long-bone fractures can document fat emboli.364,365 Brain imaging may show small hemorrhages, brain edema, and focal infarcts usually manifested by regions of gyral enhancement on CT or MRI scans. CT scans are most often normal but may show areas of hypodensity and small hemorrhages. MRI is much more sensitive and often shows abnormalities within the white matter and in border-zone regions.366 FLAIR and contrast-enhanced images are particularly helpful in showing microinfarcts.366 Figure 9-20 is an MRI FLAIR image that shows many small brain infarcts due to fat embolism in a patient who became stuporous after a leg fracture. Magnetic resonance spectroscopy can also be used to identify the presence of fat.367 In one reported patient who had fat embolism develop after a femoral fracture, magnetic resonance spectroscopy performed 35 hours after the onset of coma showed the presence of long-chain lipid resonance in high quantities in the periventricular white matter and occipital cerebral cortices of the patient with no associated lactate resonance. The lipid gradually disappeared on subsequent examinations.367

Lipid globules are sometimes found in the urine when fat stains are used. Skin, renal, and muscle biopsies may show fat globules within small skin, muscle, and renal vessels and in renal glomeruli. Cryostat frozen sections of blood also can show the presence of neutral fat. Neutral fat is most often found in patients with hypoxemia and PaCO2 of less than 60 mm Hg. Hypoxemia is very common in patients with the fat embolism syndrome. One of the most effective and specific tests for fat embolism is bronchopulmonary lavage.368,369 The technique involves microscopic examination of cells recovered by lavage and stained with a specific stain for neutral fat, such as using oil red O dye.

The mortality rate in patients with the fat embolism syndrome is quite high (as much as 50%), although the mortality rate has declined over time.1,353,356 When coma, severe blood loss, hypotension, high fever, and disseminated intravascular coagulation (DIC) are present, the mortality rate remains substantial. Necropsy of the brain of patients dying with the fat embolism syndrome shows many small-ball or ring-shaped, and perivascular hemorrhages, brain edema, and regions of microinfarction.370 Stains for fat reveal fat globules within hemorrhagic lesions and in small vessels throughout the brain. Small hemorrhages, edema, and hyaline membranes are often found in the lungs. Fat globules are also often visible in renal glomeruli, myocardium, liver, pancreas, spleen, and gastrointestinal mucosa.

Treatment of patients with the fat embolism syndrome has not been formally studied in therapeutic trials. Supportive care including oxygen administration often with assisted respiration and fluid and blood replacement is very important. Corticosteroids, heparin, and intravenous administration of 5% alcohol solutions have all been tried, but their effectiveness has not been well studied. Heparin has been used in patients with consumptive coagulopathies and also because of its posited lipolytic effect. Alcohol is also believed to have a lipolytic capability. Among these treatments, corticosteroids administration has been most frequently used.

Fat emboli syndrome

FES is a diagnostic challenge for physicians. FES may complicate widely disparate clinical conditions and may vary greatly in severity. The reported mortality ranges from 5% to 15% in multiple studies.48

FES is commonly associated with long bone and pelvic fractures and is seen more frequently in closed, rather than open, fractures. Patients with a single long bone fracture have a 1% to 3% chance of developing the syndrome, and this rate increases in correlation with the number and severity of fractures. FES has been observed in up to 33% of patients with bilateral femoral fractures. FES can occur in a variety of other clinical settings, but the risk is lower than with closed long bone fractures.49