1 Finally, rhabdomyolysis may be seen in patients with extreme alterations in body temperature due to conditions such as malignant hyperthermia, heat stroke, or neuroleptic malignant syndrome. 1 Genetic diseases including disorders of glycolysis or glycogenolysis, lipid metabolism defects, or mitochondrial disorders are rare causes of rhabdomyolysis. 10 Infections such as influenza, Epstein-Barr virus, Streptococcus pyogenes, or Staphylococcus aureus may rarely lead to rhabdomyolysis. Lipid-lowering agents, especially statins, are a common cause of rhabdomyolysis, particularly in patients with concomitant renal or liver insufficiency. 3 8 Other illicit substances such as cocaine, heroin, and phencyclidine may also be implicated in cases of rhabdomyolysis. Alcohol abuse or dependence may actually be the most common risk factor for rhabdomyolysis ethanol has direct adverse effects on muscle tissue metabolism and cellular integrity including inhibition of active transport pumps. 9 Most commonly, drugs and toxins lead to rhabdomyolysis. 1 Exertional causes of rhabdomyolysis may include extreme and prolonged exercise or seizure activity such as status epilepticus. 3 With ATP depletion, active transport pumps are no longer able to maintain low levels of intracellular calcium unregulated increases in intracellular calcium lead to activation of calcium-dependent enzymes with eventual breakdown of the muscle cell. 8Īny process that impairs ATP production by skeletal muscle and any state where skeletal muscle energy requirements exceed the available ATP may lead to rhabdomyolysis. 7 Trauma is a common cause of rhabdomyolysis, but less than 20% of all cases of rhabdomyolysis are thought to be related to direct injury metabolic or medical causes of rhabdomyolysis are more common. 3 Conditions leading to skeletal muscle ischemia, such as direct compression or compartment syndrome, may lead to irreversible damage to the muscle much of the injury may actually occur with reperfusion, in addition to injury sustained during the period of ischemia. 4 6 Patients who fall with subsequent prolonged immobilization are also at higher risk for rhabdomyolysis, particularly if their limbs are compressed by their head or torso for a significant period of time, leading to muscle hypoxia. 5 Other independent risk factors for rhabdomyolysis among trauma patients include age older than 55 years, Injury Severity Score greater than 16, penetrating trauma with vascular injury, severe extremity injury, male sex, and body mass index greater than 30 kg/m 2. 4 Patients with multisystem trauma, crush injuries involving the extremities or torso, and those with compartment syndrome of one or more extremities are at highest risk. One study has shown some degree of biochemical evidence of rhabdomyolysis (abnormal creatine kinase (CK)) among 85% of critically injured patients admitted to a trauma intensive care unit setting, although only 10% developed renal failure and only 5% required renal replacement therapy (RRT). Traumatic injuries are a common cause of rhabdomyolysis. 2 This may result from direct myocyte injury related to trauma or from metabolic disturbances affecting supply of ATP within the myocyte. 1 The pathophysiology underlying all cases of rhabdomyolysis is disruption of the myocyte cell membrane and leakage of cell contents into circulation. Rhabdomyolysis is the result of skeletal muscle breakdown with release of potentially toxic substances such as electrolytes, myoglobin, and sarcoplasmic proteins into the bloodstream.
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