Fat Embolism Syndrome

Transcription

1 Fat Embolism Syndrome Dr Jaideep Ravi DA, MD, FRCA, Senior Consultant in Anaesthesiology, Ananthapuri Hospitals and Research Institute, Trivandrum FA Zenker in 1861 first described fat embolism in a rail road worker with a thoraco-lumbar crush injury. Ernst von Bergmann in 1873 was the first to make clinical diagnosis of fat embolism. In 1911, the term 'cardiac syndrome' was used by Grandahl to describe the early acute onset of tachycardia and hypotension seen with fat embolism. He attributed this to blockage of the pulmonary arteries by fat. Although its original clinical description dates from 1873, fat embolism syndrome remains a diagnostic challenge for clinicians. Definition Fat Embolism Syndrome (FES) may be defined as a complex alteration of haemostasis which occurs as an infrequent complication of fractures of pelvis or long bones and manifests clinically as acute respiratory insufficiency. The term fat embolism indicates the often asymptomatic presence of fat globules in the lung parenchyma and peripheral circulation after long bone or other major trauma. The majority (95%) of cases occur after major trauma. Fat embolism syndrome is a serious consequence of fat emboli producing a distinct pattern of clinical symptoms and signs. It is most commonly associated with fractures of long bones and the pelvis, and is more frequent in closed, rather than open fractures. The incidence increases with the number of fractures involved. Thus, patients with a single long bone fracture have a 1 3% chance of developing the syndrome, but it has been reported in up to 33% of patients with bilateral femoral fractures. Fat embolism syndrome can also occur in relation to other trauma, for example, soft tissue injury, liposuction and bone marrow harvest. Non-trauma-related causes (e.g. acute pancreatitis, sickling crisis) are less likely to lead to fat embolism syndrome compared with those associated with trauma. An overall mortality of 5 15% has been described. Causes Fat embolism is most common after skeletal injury, and is most likely to occur in patients with multiple long bone and pelvic fractures. It is more common in patients with fractures involving the middle and proximal parts of the femoral shaft. It is more frequent in closed rather than open fractures. Causes of fat embolism Traumatic: Long bones fractures Pelvic fractures Blunt trauma Soft tissue injury ( e.g. chest compression with or without rib fractures) Bone marrow harvesting and transplant Joint reconstruction Liposuction Non traumatic: Acute pancreatitis Burns Cardiopulmonary bypass Decompression sickness

2 Sickle cell crisis Parenteral lipid infusion Diabetes mellitus Alcoholic liver disease Osteomyelitis and panniculitis Steroid therapy Bone tumour lysis Cyclosporine A solvent Pathophysiology The mechanism producing fat embolism syndrome is not clearly understood; mechanical and biochemical causes have been proposed. Mechanical theory According to this theory, proposed by Gauss in 1924, trauma to long bones releases fat droplets by disrupting fat cell in the fractured bone or in adipose tissue. These fat droplets enter the torn venules in areas of trauma. Fractures of marrow-containing bone have the highest incidence of fat embolism syndrome and cause the largest volume of fat emboli. This may be because the disrupted venules in the marrow remain tethered open by their osseous attachments. Fat droplets are then transported to pulmonary vascular bed where large fat globules result in mechanical obstruction and are trapped as emboli in the lung capillaries. Small fat droplets may pass through the lung and reaches systemic circulation causing embolization to brain, skin, kidney or retina. Another way in which these fat droplets pass to the systemic circulation is pulmonary precapillary shunts and existing pathological venous-arterial communication such as patent foramen ovale. However, this theory does not sufficiently explain the hr delay in the development of FES after the acute injury. Biochemical theory This theory, proposed by Lehmann and Moore in 1927, states that there are a number of biochemical mechanisms potentially involved in the development of FES. The biochemical theory suggests that the clinical manifestations of FES are attributable to a proinflammatory state. Bone marrow fat is broken down by tissue lipases, resulting in high concentrations of glycerol and toxic free fatty acids. These intermediate products lead to endorgan dysfunction. In the lung, toxic injury to pneumocytes and pulmonary endothelial cells causes vasogenic and cytotoxic oedema as well as haemorrhage. The damaged pulmonary endothelium triggers a proinflammatory cytokine cascade, leading to the development of acute lung injury or acute respiratory distress syndrome. Biochemical studies on patients with confirmed FES support several aspects of this theory. Patients with FES have elevated levels of plasma phospholipase A2, proinflammatory cytokines (including tumour necrosis factor-alpha, interleukin-1, and interleukin-6), and free radicals. These proinflammatory intermediates may explain FES in nontraumatic settings as well as the observed delay of hours to days from the traumatic insult until the onset of clinical findings in FES. The pathophysiology of most cases of FES combines these mechanical and biochemical processes. This interplay is exemplified by the manifestations of FES occurring in both the arterial and venous circulation. The petechial rash appears to be caused by post obstructive haemorrhage at the capillary level but in many patients may also result from a systemic inflammatory and prothrombotic state. Clinical presentation FES is characterized by multisystem dysfunction typically presenting 12 to 72 hours after the initial insult. The classic triad of FES includes hypoxemia, neurological abnormalities, and petechiae.

3 Respiratory changes are often the first clinical feature to present. Dyspnoea, tachypnoea, and hypoxaemia are the most frequent early findings. The severity of these symptoms varies but a number of cases may progress to respiratory failure and a syndrome indistinguishable from acute respiratory distress syndrome (ARDS) may develop. Neurological features resulting from cerebral embolism frequently present in the early stages. Cerebral emboli produce neurological signs in up to 86% of cases and often occur after the development of respiratory distress. The changes range across a wide spectrum from mild confusion and drowsiness through to severe seizures. The more common presentation is with an acute confusional state but focal neurological signs, including hemiplegia, aphasia, apraxia, visual field disturbances, and anisocoria, have been described. Seizures and decorticate posturing have also been seen. Almost all neurological deficits are transient and fully reversible. The characteristic petechial rash may be the last component of the triad to develop. It occurs in up to 60% of cases and is due to embolization of small dermal capillaries leading to extravasation of erythrocytes. This produces a petechial rash in the conjunctiva, oral mucous membrane, and skin folds of the upper body, especially the neck and axilla. It does not appear to be associated with any abnormalities in platelet function. The rash appears within the first 36 h and is self-limiting, disappearing completely within 7 days. A number of minor features of fat embolism syndrome may be present and these appear to result from the release of toxic mediators secondary either to the initial injury or to dysfunctional lipid metabolism. These include pyrexia, tachycardia, myocardial depression, ECG changes indicative of right heart strain, soft fluffy retinal exudates with macular oedema scotomata (Purtscher s retinopathy), coagulation abnormalities (which mimic disseminated intravascular coagulation) and renal changes presenting as oliguria, lipiduria, proteinuria, or haematuria. Diagnosis Diagnosis is usually made on the basis of clinical findings but biochemical changes may be of value. The diagnosis is made by recognizing the characteristic clinical syndrome in the context of supportive imaging and a predisposing insult. An unexplained anaemia (70% of patients) and thrombocytopenia (platelet count < /mm 3 in up to 50% of patients) are often found. Serum lipase concentration increases after bone injuries and is often misleading. Cytological examination of urine, blood and sputum with Sudan or Oil Red O staining may detect fat globules that are either free or in macrophages. Hypocalcaemia, due to binding of the free fatty acids to calcium, and elevated serum lipase have also been reported. Directly sampling the pulmonary system for lipids has shown promise as a potential diagnostic tool. In one study, bronchoalveolar lavage samples with >30% of alveolar cells staining for neutral fat was strongly associated with a clinical diagnosis of FES. Detection of fat in blood aspirated from a wedged pulmonary artery catheter lacks the sensitivity and specificity to add significant diagnostic certainty and is not typically used in clinical practice. The chest X-ray is often normal initially but in some patients bilateral fluffy shadows develop as respiratory insufficiency worsens. A minority has diffuse or patchy air space consolidation, due to oedema or alveolar haemorrhage. Focal areas of ground glass opacification with interlobular septal thickening are generally seen on chest CT but ill-defined centrilobular and subpleural nodules representing alveolar oedema, microhaemorrhage and inflammatory response secondary to ischaemia and cytotoxic emboli may be seen. MRI of the brain can reveal a star-field pattern of diffuse, punctate, hyperintense lesions on diffusion-weighted imaging. Given the absence of a gold standard diagnostic test or pathognomonic feature, a number of authors have proposed clinical diagnostic criteria. The most frequently cited are Gurd s Criteria.

4 Gurd s criteria Major criteria Axillary or subconjunctival petechiae Respiratory symptoms with radiographic changes Central nervous system signs unrelated to trauma or other condition Minor criteria Tachycardia Pyrexia Retinal changes (fat or petechiae) Renal abnormalities (oliguria, anuria or lipiduria) Sudden inexplicable drop in haematocrit or platelet values Increasing ESR Fat globules present in the sputum For the diagnosis of fat embolism syndrome, at least one major and four minor criteria must be present. The reliability of these criteria have been questioned and other schemes based more on respiratory features alone have been proposed. Lindeque s criteria Sustained PaO 2 <8KPa Sustained PaCO 2 >7.3KPa or a ph <7.3 Sustained respiratory rate >35 breaths/min, despite sedation Increased work of breathing: dyspnoea, accessory muscle use, tachycardia and anxiety More recently, a fat embolism index has been proposed as a semi-quantitative means of diagnosing fat embolism syndrome, in which there are several clinical features. Each one is given a particular score. A score of >5 is required for a positive diagnosis. Schonfield s criteria Petechiae 5 Chest X-ray changes (diffuse alveolar infiltrates) 4 Hypoxemia (PaO2<9.3 KPa) 3 Fever (38 C) 1 Tachypnoea (>30 bpm) 1 Tachycardia 1 Cumulative score >5 required for diagnosis Treatment and prevention There is no specific therapy for fat embolism syndrome (FES) prevention, early diagnosis, and adequate symptomatic treatment are of paramount importance. Supportive care includes maintenance of adequate oxygenation and ventilation, stable haemodynamics, blood products as clinically indicated, hydration, prophylaxis of deep venous thrombosis and stress-related gastrointestinal bleeding, and nutrition. The goals of pharmacotherapy are to reduce morbidity and prevent complications. Supportive care is the mainstay of therapy for clinically apparent fat embolism syndrome. Mortality is estimated to be 5 15% overall, but most patients will recover fully. Early immobilization of fractures reduces the incidence of fat embolism syndrome and the risk is further reduced by operative correction rather than conservative management. Another strategy to prevent fat embolism syndrome is to limit the elevation in intraosseous pressure during orthopaedic procedures, in order to reduce the intravasation of intramedullary fat and other debris.

5 Heparin and corticosteroids have been proposed as treatments but have not reliably demonstrated improved morbidity or mortality. Systemic anticoagulation has been considered as a potential therapy for FES. Heparin stimulates lipase activity and therefore may accelerate the clearance of lipids from circulation, but the resultant increase in free fatty acids could exacerbate the underlying proinflammatory physiology. Furthermore, anticoagulation in the setting of trauma and pre-existing hematologic abnormalities may prove harmful. The use of corticosteroid prophylaxis is controversial, largely because it is difficult to definitively prove efficacy in a condition with a low incidence, unclear risk factors, low mortality and a good outcome with conservative management. Nevertheless, a number of studies report decreased incidence and severity of fat embolism syndrome when corticosteroids are given prophylactically. In cases of fulminant FES, corticosteroids may be considered. However, there is insufficient evidence to support routine administration of corticosteroids for the majority of patients with FES. Supportive ICU level care is standard. Most patients are severely hypovolemic and require fluid resuscitation. Supportive correction of hypoxemia with supplemental oxygen or mechanical ventilation is often necessary while the patient recovers. If central nervous system dysfunction is present, frequent neurological examinations are required and intracranial pressure monitoring should be considered. Vasopressors may be required. Prognosis The outcome of patient with FES is generally favourable. Mortality has decreased with advances in supportive care and is <10% currently. Pulmonary, neurological and dermatological manifestations of FES generally completely resolve. References 1. Von Bergmann E. Ein fall todlicher fettembolie. Berl Klin Wchenschr 1873; 10: 385. Cited by Sevitt S. Fat Embolism. Butterworth: London, A Gupta, CS Reilly. Fat Embolism. Contin Educ Anaesth Crit Care Pain (2007) 7 (5): Mellor A, Soni N. Fat embolism. Anaesthesia 2001; 56: Ravi P Mahajan. Acute lung injury: options to improve oxygenation. Contin Educ Anaesth Crit Care Pain (2005) 5 (2): Schonfeld SA, Ploysongsang Y, DiLisio R et al. Fat embolism prophylaxis with corticosteroids. Ann Intern Med 1983; 99: JW O Higgins. Fat Embolism. Br J Anaesth (1970) 42 (2): M. Igarashi, A. Kita, K. Nishikawa, M. Nakayama, K. Tsunoda, A. Namiki. Use of percutaneous cardiopulmonary support in catastrophic massive pulmonary fat embolism. Br J Anaesth (2006) 96 (2): E Kosova, B Bergmark, G Piazza. Fat Embolism Syndrome. Circulation (2015) 131: Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg (1970) 52B: Gossling HR, Pellegrini VD. Fat Embolism Syndrome: A review of the pathophysiology and physiological basis of treatment. Clin Orthop. (1982) 165: 68-82