RHABDOMYOLYSIS DEFINITION Rhabdomyolysis is a syndrome caused by injury to skeletal muscles and the resultant leakage of muscle cell contents (myoglobin, potassium, phosphate, etc.) into the plasma. TOXIC CAUSES Rhabdomyolysis has been associated with a variety of toxins and drugs. They can either exert a direct toxic effect on muscles (metabolic poisons) or indirectly predispose to rhabdomyolysis. Direct toxic effect: Amatoxins Carbon monoxide Colchicine Ethylene glycol Snakebite Indirect effect: Excessive muscular hyperactivity or rigidity (dystonia) Prolonged seizures Hyperthermia Muscular compression from prolonged immobility (coma) NON-TOXIC CAUSES Coma or prolonged immobility from any cause Direct Muscle Injury Excessive muscular activity Endurance sporting activities Seizures Immunological Dermatomyosits Polymyositis Ischaemic Muscle injury Crush injury Vascular occlusion Metabolic Hypokalaemia Hypophophataemia Viral Infections Coxsackie Influenza CLINICAL FEATURES The clinical presentation is extremely variable. In conscious patients, the main complaint may be muscle tenderness, stiffness and cramping, accompanied by weakness and loss of function. However, myalgia may be absent or minimal initially (upon admission). In comatose patients, the finding of limb induration should suggest rhabdomyolysis. Skin changes due to ischaemic tissue injury (discoloration, blisters) may be present on the affected area. Physical examination may reveal a "woody" muscle swelling which may worsen after parenteral rehydration. Severe muscle swelling can result in a compartment syndrome, with absent pulses. Dark (red-brown) urine is a classical manifestation of rhabdomyolysis. Signs of dehydration (due to sequestration of fluid in damaged muscles) may be present along with oliguria. In rhabdomyolysis due to severe poisoning, muscle signs can be overlooked if signs indicative of the underlying disorder (e.g., extreme agitation, seizures, hyperthermia) dominate the clinical picture. Signs related to complications of rhabdomyolysis (e.g., hyperkalaemia, acute renal failure, metabolic acidosis, disseminated intravascular coagulation and, rarely, respiratory failure) can also constitute the main clinical findings. RELEVANT INVESTIGATIONS A serum creatine phosphokinase activity greater than five times the normal value (in the absence of heart and brain disease) is the most sensitive indicator of rhabdomyolysis. Myoglobinaemia may result from the leakage of myocyte contents into the plasma. When muscle destruction is acute, extensive myoglobinuria can occur and may cause a visible discoloration of the urine (red-brown). A positive orthotoluidine reaction (Hematest),in the absence of red blood cells in the urine, confirms the presence of myoglobinuria. The following laboratory findings can be present: hyperkalaemia, hypocalcaemia, hyperphosphataemia, hyperuricaemia, elevated blood urea and serum creatinine, elevated AST (SGOT) and LDH activities. The creatinine may be disproportionately elevated in relation to renal insufficiency because of the release of preformed creatine from damaged muscles. TREATMENT The first aim of treatment is to support vital functions. Diazepam In case of excessive muscular activity (e.g. combativeness, seizures), initiate treatment with Diazepam (5 to 10 mg slowly IV, up to a maximum of 30 mg). Fluids Crystalloid infusion should be given to maintain a high urine output (> 3 - 4 mLs/hr). Furosemide/Mannitol Diuretics: Furosemide or Mannitol may be used when administration of fluids alone is inadequate. Sodium Bicarbonate Urine alkalinization has been proposed for the prevention of myoglobin nephrotoxicity, but its effectiveness has not been demonstrated conclusively. Calcium Salts Hypocalcaemia, a common finding in rhabdomyolysis, is rarely symptomatic when present alone, and therefore does not necessitate treatment. Haemodialysis Dialysis is indicated whenever acute renal failure occurs and/or life-threatening complications (e.g. hyperkalaemia) are present. Fasciotomy Fasciotomy is rarely indicated and may be associated with serious complications. CLINICAL COURSE AND MONITORING Careful clinical monitoring of vital signs Urine output Cardiac rhythm Serum sodium, potassium, and calcium Haematocrit/Haemoglobin Arterial blood gases Creatine phosphokinase activity Serum creatinine and blood urea AST (SGOT) and LDH Hematest (orthotoluidine reaction): if Hematest is positive, haematuria must be ruled out by microscopic examination of the urine. Platelet count, fibrinogen level, partial thromboplastin and prothrombin times to detect either thrombocytopenia or disseminated intravascular coagulation. POTENTIAL COMPLICATIONS/SEQUELAE Prolonged muscle weakness is the most frequent complaint following rhabdomyolysis. Peripheral neuropathy with permanent neurologic deficits can result from neuronal ischaemia due to a compartment syndrome. The acute renal failure secondary to rhabdomyolysis has a good prognosis when early treatment is performed. AUTHOR(S)/REVIEWERS Author: Dr T. Della Puppa, Centro Antiveleni, Milano, Italy. Peer Review: Sao Paulo 9/94, Cardiff 3/95, Berlin 10/95: A. Wong, T. Meredith, V. Danel.