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.
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 filtration of 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 (especially statins). The presence of kidney or liver dysfunction, 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. Concurrent use of drugs that inhibit cytochrome P450 (including protease inhibitors, erythromycin or clarithromycin, itraconazole, diltiazem, and verapamil) with statins (except pravastatin or rosuvastatin) as well as concurrent use of niacin and fibrate-containing therapy can increase the risk of development of rhabdomyolysis.
Patients with rhabdomyolysis may have myalgias or weakness or both, though it is not uncommon for them to be asymptomatic. Urine may appear dark.
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.
The classic laboratory finding in rhabdomyolysis is a urine dipstick test that is positive for “blood” but without red blood cells on microscopy. 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).
The mainstay of treatment is aggressive volume repletion with 0.9% normal saline (ie, more than 4 L/day) and removal of offending medications if 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 ...