Rhabdomyolysis

Key Features

• Associated with crush injuries to muscle, immobility, drug toxicities, and hypothermia

• Usually markedly elevated muscle enzymes

Clinical Findings

• Defined as a syndrome of acute necrosis of skeletal muscle associated with myoglobinuria and markedly elevated creatine kinase levels

• Many patients are volume-contracted and, therefore, oliguric renal failure is encountered routinely due to the filtration of excessive quantities of myoglobin in the setting of hypovolemia

• Use of statins is an important cause of rhabdomyolysis

  • The cytochrome P450 liver enzymes metabolize all statins except for pravastatin and rosuvastatin

  • Drugs that block the action of cytochrome P450 include protease inhibitors, erythromycin or clarithromycin, itraconazole, diltiazem, and verapamil. Use of these drugs concomitantly with the statins (but not pravastatin or rosuvastatin) can increase the risk of development of rhabdomyolysis.

  • The likelihood of rhabdomyolysis also increases when statins are used with niacin and fibric acids (gemfibrozil, clofibrate, and fenofibrate)

• Acute tubular necrosis is a common complication of rhabdomyolysis and is due to the toxic effects of filtering excessive quantities of myoglobin in the setting of hypovolemia

• Compartment syndrome, disseminated intravascular coagulation, and cardiac arrhythmias are serious but less common complications of rhabdomyolysis

• Rhabdomyolysis is an uncommon complication of polymyositis, dermatomyositis, and the myopathy of hypothyroidism, despite the high levels of creatine kinase often seen in these conditions.

Diagnosis

• Often there is little evidence for muscle injury on clinical assessment of the patients with rhabdomyolysis; specifically, myalgias and weakness are usually absent

• The first clue to muscle necrosis in such individuals may be a urine dipstick testing positive for "blood" (actually myoglobin) in the absence of red cells on microscopy

  • This myoglobinuria results in a false-positive reading for hemoglobin

  • Urine tests for myoglobin are insensitive, however, and are positive in only 25% of patients with rhabdomyolysis

  • Such an abnormality should prompt determination of the serum creatine kinase level, which invariably is elevated (usually markedly so)

• Other commonly encountered laboratory abnormalities include

  • Elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LD) (due to release of these enzymes from skeletal muscle)

  • Hyperkalemia

  • Hypocalcemia

• The massive acute elevations of muscle enzymes peak quickly and usually resolve within days once the inciting injury has been removed

Treatment

• Vigorous fluid resuscitation (eg, 4–6 L/day but often more in the setting of severe crush injuries) is indicated

• Urine alkalinization (to minimize precipitation of myoglobin within tubules) has been recommended to reduce kidney injury but definitive evidence is lacking

• Myopathic complications of statins usually resolve within several weeks of discontinuing the drug