Rhabdomyolysis is a syndrome that involves skeletal muscle injury, necrosis, and release of intracellular contents, including myoglobin and creatinine kinase. If left untreated, complications can occur such as renal failure, compartment syndrome, and peripheral neuropathy.
Obtaining a history which includes risk factors for the development of rhabdomyolysis should increase the suspicion for this syndrome. Importantly, classic signs of rhabdomyolysis may not always be present.
Historical clues to suggest a patient may be at risk for rhabdomyolysis include the following: injuries that can cause compartment syndrome or prolonged muscular compression, including traumatic crush injuries, acutely casted long-bone fractures, heat stroke, electrical injuries, and lightning strikes; prolonged immobilization; drug intoxication with numerous agents including amphetamines, phencyclidine (PCP), cocaine, or antihistamines; excessive muscular activity, seizures, dystonia, or delirium tremens; and diseases such as dermatomyositis, polymyositis, or neuroleptic malignant syndrome. Commonly prescribed medications associated with the development of rhabdomyolysis include antipsychotics, lipid-lowering agents (ie, statins and clofibrate), narcotics, zidovudine, and colchicine.
Classically, patients complain of myalgias, muscle stiffness, malaise, and a low-grade fever. Dark-colored urine often occurs with myoglobinuria. However, these classic findings may be absent in up to 50% of patients with rhabdomyolysis syndromes. Other nonspecific symptoms may include nausea, vomiting, abdominal pain, or palpitations. Signs and symptoms of renal failure can occur as complications from rhabdomyolysis.
The postural muscles of the calves, thighs, and lower back are the most often involved muscle groups, and the involved muscles can be localized or diffuse. The involved muscles are often tender to palpation, but objective swelling may be subtle or absent, especially prior to rehydration.
There are many complications of rhabdomyolysis including acute kidney injury, which can be either oliguric (most commonly), or nonoliguric. Myoglobin breakdown, which occurs in the setting of dehydration and aciduria (pH < 5.6), results in exposure of ferrihemate, which is nephrotoxic. The risk of acute kidney injury correlates poorly with the total rise in creatinine kinase (CK) or amount of myoglobinuria. Additional complications include metabolic derangements including hyperkalemia, hyperuricemia and hypocalcemia, mechanical complications, and occasionally disseminated intravascular coagulation (DIC). Hypercalcemia and hypophosphatemia occur later. Mechanical complications of rhabdomyolysis include both an acute compartment syndrome, as well as peripheral neuropathy due to muscular edema with subsequent nerve compression.
The diagnosis of rhabdomyolysis typically requires a serum CK to be elevated at least 5-fold greater than the upper limit of normal, excluding cardiac or neurologic causes of the elevation. In general, the serum CK will begin to rise 2 to 12 hours after the initial muscle injury, and will peak after 1 to 3 days, in the absence of ongoing injury. The value should decline approximately 39% daily. Myoglobinuria can be detected once plasma myoglobin concentrations exceed 1.5 milligrams/dL. A dark discoloration of the urine or unexplained elevations of lactate dehydrogenase or aminotransferases may be additional clues to the diagnosis.
Myoglobin contains heme. Qualitative tests, such as the urine dipstick, which uses an orthotoluidine reaction, cannot differentiate between hemoglobin, myoglobin, and red blood cells. Thus, the presence of blood on a urine dipstick with only a few or no corresponding red blood cells on microscopy also suggests the diagnosis of rhabdomyolysis.
All patients suspected of having rhabdomyolysis should have a CK, electrolytes, blood urea nitrogen, calcium, and urinalysis obtained. Additional laboratory tests should be obtained based on the clinical scenario.