Rhabdomyolysis

Key Features

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

• Usually markedly elevated muscle enzymes and electrolyte abnormalities

• Release of myoglobin leads to direct renal toxicity

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

  • Acute tubular necrosis is a common complication due to filtration of excess myoglobin, leading to tubular obstruction from pigmented casts and intrarenal vasoconstriction

• Rhabdomyolysis can result from

  • Crush injuries

  • Prolonged immobility

  • Seizures

  • Substance abuse (eg, cocaine)

  • Medications (especially statins)

  • Concomitant volume depletion in these settings increases risk of rhabdomyolysis

  • Statins are an important cause of rhabdomyolysis

    • Rhabdomyolysis is increased when statins are taken with concurrent kidney or liver disease, diabetes, or hypothyroidism

    • 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 (except pravastatin or rosuvastatin) can increase the risk of development of rhabdomyolysis

    • Rhabdomyolysis risk also increases when statins are used with niacin and fibrate-containing therapy

Diagnosis

• Myalgias and/or weakness may be present, but commonly asymptomatic

• Urine may appear dark

• Classic laboratory finding is urine dipstick testing positive for "blood" (actually myoglobin) in the absence of red cells on microscopy

  • This false-positive result is due to detection of myoglobin rather than hemoglobin

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

• Other commonly encountered laboratory abnormalities include

  • Serum creatine kinase commonly >16,000 to 50,000 IU/L in clinically important rhabdomyolysis

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

  • Hyperkalemia

  • Hyperphosphatemia

  • Hyperuricemia

  • 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 with 0.9% normal saline (> 4 L/day) is mainstay of treatment

• Removal of offending medications

• Use of mannitol and urine alkalinization have not been proven to change outcomes

• Calcium

  • As patients recover, calcium can translocate from tissues to plasma

  • Early calcium administration for hypocalcemia is not recommended unless the patient is symptomatic, or the level is exceedingly low in an unconscious patient

  • Calcium repletion can cause precipitation of calcium phosphate given the frequently concurrent hyperphosphatemia

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