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Letters to the Editor
December 1998

Critical Illness Myopathy, Steroids, and Cytochrome P450

Arch Neurol. 1998;55(12):1591. doi:

Critical illness myopathy is a poorly understood, but increasingly recognized clinical syndrome that characteristically occurs in the intensive care unit among patients who have been treated with multiple drugs (particularly neuromuscular-blocking agents and antibiotics) and high-dose steroids.16 This rapidly progressive myopathy is characterized by muscle fiber atrophy and/or necrosis, often selectively affecting type 2 myofibers (Figure 1). Steroids are potent inducers of some forms of cytochrome P450.7 Recent studies8 suggest that cytochrome P450 is associated with skeletal muscle sarcoplasmic reticulum. Induction of cytochrome P450 and the consequent formation of reactive intermediates in the metabolism of some compounds result in the activation of calcium-release channels.9 Critical illness myopathy may result from steroid induction of cytochrome P450 associated with sarcoplasmic reticulum. The consequent production of reactive intermediate metabolites of other drugs given in the setting of critical illness then causes pathologic activation of calcium-release channels in sarcoplasmic reticulum and consequent muscle injury. The differences between muscle fiber types in calcium handling may account for the preferential involvement of type 2 muscle fibers in both steroid myopathy8 and critical illness myopathy.

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