The hallmark of critical illness myopathy is weakness that is typically diffuse in distribution, affecting both limb and neck muscles [7]. As is typical of most myopathic disorders, weakness tends to have a proximal predominance in the limbs, but it may also involve distal muscles profoundly. Tendon reflexes tend to be depressed but present, and on occasion, may be absent, possibly due to a generalized reduction in membrane excitability that occurs in sepsis [8]. There may be facial muscle involvement, and rarely, extraocular muscles are affected [9]; other muscles supplied by cranial nerves are usually spared. A serious and common complication of the myopathy is failure to wean from a ventilator due to marked weakness of the diaphragm. Although the majority of affected patients are adults, severe myopathic muscle weakness may occur in children who receive organ transplants [10].

Critical illness myopathy develops in up to one-third of patients treated for status asthmaticus in the ICU; and in this population, intravenous corticosteroids and neuromuscular blocking agents are considered major risk factors [11]. Occasionally, the myopathy develops in patients who have received high-dose corticosteroids alone, without neuromuscular blocking agents, or in patients who have received neither corticosteroids nor neuromuscular blocking agents, but the latter group typically has severe systemic illness with multiorgan failure and sepsis [8]. Overall, critical illness myopathy accounts for 42% of weakness among patients in the surgical and medical ICU setting [12].

Serum creatine kinase (CK), electromyography (EMG), and muscle biopsy are the most important and revealing studies in the diagnosis of ICU-acquired muscle weakness. An elevated CK level helps to support the diagnosis of a myopathic cause of weakness in an ICU patient, but in the myopathy of intensive care, the CK rise, which is found in about 50% of affected patients, only occurs early in the course of the illness, peaks within a few days of onset, and then declines back into the normal range [7].

Myosin loss and muscle fiber necrosis probably contribute to persisting weakness. Myosin loss is characteristic of critical illness myopathy, and is essentially pathognomonic of the disorder. Corticosteroids may cause the loss of myosin, but other factors trigger the process, such as an abnormal neuromuscular junction caused by pharmacologic blockade in ICU patients [7]. Consistent with this hypothesis is the observation that a patient with myasthenia developed loss of myosin thick filaments after receiving high-dose corticosteroids [15], and that in an animal model of dexamethasone treatment plus denervation, there was a severe preferential depletion of thick filaments, leading to a reduction in muscle fiber size [16]. Some patients who are not exposed to administered corticosteroids or neuromuscular blocking agents, but who are systemically ill, often with metabolic acidosis, can also develop the myopathy of intensive care. Acidosis may stimulate glucocorticoid production, lead to an increase in muscle protein degradation, and trigger thick filament loss [7]. Finally, as noted earlier, muscle membrane inexcitability is noted in some patients with the disorder. In an animal model of ICU-related myopathy (rats treated with corticosteroids for 7 to 10 days after denervation of muscle in one leg), intracellular recordings in individual muscle fibers demonstrate that many fibers become unable to generate action potentials [17]. Paralysis appears to be due to abnormal inactivation of sodium channels, which suggests that the myopathy of intensive care may be, in part, an acquired disease of ion channel gating.