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ESSENTIALS OF DIAGNOSIS
Associated with crush injuries to muscle, immobility, drug toxicities, and hypothermia.
Characterized by serum elevations in muscle enzymes, including creatine kinase, and marked electrolyte abnormalities.
Release of myoglobin leads to direct renal toxicity.
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Rhabdomyolysis is a syndrome of acute skeletal muscle necrosis, leading to myoglobinuria and markedly elevated creatine kinase levels. Acute tubular necrosis is a common complication of rhabdomyolysis and is 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 can also occur. Rhabdomyolysis can result from crush injuries, prolonged immobility, seizures, substance abuse (eg, cocaine), and medications. Among medications, statins are an important cause of rhabdomyolysis. The presence of compromised kidney and liver function, diabetes mellitus, and hypothyroidism increase the risk of rhabdomyolysis in patients taking statins. 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, itraconazole, clarithromycin, diltiazem, and verapamil. Concurrent use of these drugs with statins (but not pravastatin or rosuvastatin) as well as concurrent use of niacin and fibrate-containing therapy can increase the risk of development of rhabdomyolysis.
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A. Symptoms and Signs
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Patients with rhabdomyolysis may have myalgias or weakness or both, though it is not uncommon for them to be asymptomatic. Urine may appear dark.
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B. Laboratory Findings
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Rhabdomyolysis of clinical importance commonly occurs with a serum creatine kinase greater than 20,000–50,000 international units/L; one study showed that 58% of patients with AKI from rhabdomyolysis had creatine kinase levels greater than 16,000 international units/L, while only 11% of patients without kidney injury had creatine kinase values greater than 16,000 international units/L. Often, there are elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LD) (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.
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The classic laboratory finding in rhabdomyolysis is a urinary dipstick test that is positive for “blood” but without red blood cells on urinary sediment. This false-positive result is due to detection of myoglobin. Additionally, clinically meaningful rhabdomyolysis causes injured muscle cells to release intracellular components, leading to electrolyte derangements (including hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia).
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The mainstay of treatment is aggressive volume repletion with 0.9% normal saline (ie, more than 4 L/day) and removal of offending agents if medications are thought to have caused the disorder. Adjunctive treatments with mannitol and alkalization of the urine have not been proven to change outcomes in human trials. As patients recover, calcium can move back from tissues to plasma, so early exogenous calcium administration for hypocalcemia is not recommended unless the patient is symptomatic or the level becomes exceedingly low in an unconscious patient; ...