Rhabdomyolysis is the destruction of skeletal muscle, caused by any mechanism that results in injury to myocytes and their membranes. Direct muscle injury and genetic and biochemical factors can predispose to rhabdomyolysis. Acute necrosis of skeletal muscle fibers and the leakage of cellular contents into the circulation result in myoglobinuria.

Several classification systems have been developed to characterize the numerous causes of rhabdomyolysis. None of these systems is universally recognized, and each has its limitations.

Table 89-1 lists commonly recognized conditions associated with rhabdomyolysis. In general, the most common causes of rhabdomyolysis in adults appear to be alcohol and drugs of abuse, followed by medications, muscle diseases, trauma, neuroleptic malignant syndrome, seizures, immobility, infection, strenuous physical activity, and heat-related illness.^1,2 A host of drugs and toxins have been identified that are associated with or causative of rhabdomyolysis.³ Multiple causes are present in more than half of patients.¹ In children, rhabdomyolysis is less common and is thought to be more benign.³ In one study of children, the most common causes of nonrecurrent rhabdomyolysis were trauma, viral myositis, and connective tissue disease.⁴ For adults and children, inherited metabolic disorders should be suspected with recurrent episodes of rhabdomyolysis, especially if associated with exercise intolerance.

Patients in coma are at risk for rhabdomyolysis from unrelieved pressure on gravity-dependent body parts. Alcohol consumption can result in rhabdomyolysis secondary to coma-induced muscle compression and a direct toxic effect. Nutritional compromise, hypokalemia, hypomagnesemia, and hypophosphatemia, all common in alcoholics, increase the risk of rhabdomyolysis. Alcohol and drugs are thought to play a role in most cases of rhabdomyolysis in adults.¹ Drugs of abuse are commonly implicated in acute rhabdomyolysis, and many commonly prescribed medications have been associated as well.² Statin-related myopathies include myalgias with or without elevation of creatine kinase level, muscle weakness, and rhabdomyolysis. Statin-related rhabdomyolysis is rare, varies with the particular statin, and is also dose related. Drug combinations, including combinations with cyclosporine, macrolide antibiotics, warfarin, digoxin, and dual statin therapy, carry an increased risk for rhabdomyolysis.^3,5

A number of bacterial and viral infections have been associated with rhabdomyolysis.³ Strenuous physical activity, as seen in athletes, marathon runners, military recruits, and outdoor laborers, is a common cause. Physical activity that produces high-force eccentric contractions, such as strength training or heavy lifting, leads to greater breakdown in muscle and higher levels of creatine kinase than concentric contractions, such as endurance-based exercises.⁶ Factors that increase the risk in this group of patients include poor physical conditioning, inadequate fluid intake, wearing of restrictive clothing, high ambient temperatures, and high humidity levels.⁶

PATHOPHYSIOLOGY

Rhabdomyolysis is a syndrome characterized by injury to skeletal muscle with subsequent effects from the release of intracellular contents. These contents include myoglobin, creatine kinase, aldolase, lactate dehydrogenase, aspartate aminotransferase, and potassium. Although numerous causes of rhabdomyolysis have been described, the common terminal event appears to involve the disruption of the Na⁺K⁺ATPase pump and calcium transport, which results in increased intracellular calcium and subsequent muscle cell necrosis. In addition, calcium activates phospholipase A₂ and various vasoactive molecules and proteases and induces the production of free oxygen radicals.^3,7

The presenting symptoms of rhabdomyolysis are usually acute in onset and include myalgias, stiffness, weakness, malaise, low-grade fever, and dark (usually brown) urine. Muscle symptoms, however, may be present in only half of cases.⁴ Nausea, vomiting, abdominal pain, and tachycardia can occur in severe rhabdomyolysis. Mental status changes may develop from urea-induced encephalopathy. Swelling and tenderness of the involved muscle groups and hemorrhagic discoloration of overlying skin may be observed but are not common. Muscle involvement may be localized or diffuse, depending on the cause. Commonly, the postural muscles of the thighs, calves, and lower back are involved. Muscle swelling may not become apparent until after rehydration with IV fluids. An important point to remember is that acute rhabdomyolysis may be present without any of these signs or symptoms, and the patient may have normal findings on physical examination. For this reason, the diagnosis often is made only after soliciting a historical clue (e.g., recent cocaine use) or finding an elevated serum creatine kinase level or the presence of dark urine on routine laboratory testing.