Rhabdomyolysis

Essentials of Diagnosis

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

• Characterized by serum elevations in muscle enzymes, including creatinine kinase (CK), and marked electrolyte abnormalities

• Release of myoglobin leads to direct renal toxicity

General Considerations

• Defined as a syndrome of acute skeletal muscle necrosis, leading to myoglobinuria and markedly elevated creatine kinase levels

• Can result from crush injuries, prolonged immobility, seizures, substance abuse (eg, cocaine), and medications

• The presence of compromised kidney and liver function, diabetes mellitus, and hypothyroidism increase the risk of rhabdomyolysis in patients taking statins

• Myalgias

• Weakness

• May be asymptomatic

• Use of statins is an important cause of rhabdomyolysis

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

  • The following medications block the action of cytochrome P450 and can increase the risk of rhabdomyolysis when used with statins (but no increased risk when used with pravastatin or rosuvastatin):

    • Protease inhibitors

    • Erythromycin

    • Itraconazole

    • Clarithromycin

    • Diltiazem

    • Verapamil

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

• Serum CK > 20,000–50,000 international units/L

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

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

• Urine may appear dark

• Urinary dipstick test

  • Positive for "blood" but without red blood cells on urinary sediment

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

• Injured muscle cells release intracellular components, leading to electrolyte derangements, including

  • Hyperkalemia

  • Hyperphosphatemia

  • Hyperuricemia

  • Hypocalcemia

• The mainstay of treatment is

  • Aggressive volume repletion with 0.9% normal saline (i.e. > 4 L/day)

  • Removal of offending agents if medications are thought to have caused the disorder

• Adjunctive treatments with mannitol and alkalinization of the urine have not been proven to change outcomes in human trials

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

Complications

• Acute tubular necrosis due to the toxic effects of filtering excessive quantities of myoglobin, which can be exacerbated by volume depletion

• Distal tubular obstruction from pigmented casts and intrarenal vasoconstriction

Prognosis

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

When to Refer

• Clinically meaningful rhabdomyolysis requires immediate attention and inpatient management, so affected patients should not be referred to outpatient nephrology consultation unless to follow up after a hospital admission

When to Admit

• Patients whose serum CK levels are > 15,000–20,000 international units/L, or patients with AKI or electrolyte derangements, should be admitted for fluid repletion and serial monitoring of CK and electrolytes