Acute myopathy has been increasingly recognized as a significant complication of patients cared for in the intensive care unit (ICU). The term critical illness myopathy (CIM) or ICU Myopathy is now used to describe a general syndrome of muscle dysfunction occurring in the critically ill patient, with subtypes of CIM also being defined.
The major feature of CIM is diffuse, flaccid weakness of limb, neck, and facial muscles, as well as the diaphragm. Ophthalmoplegia may be present and tendon reflexes are often depressed. The timing of critical illness myopathy onset is difficult to determine, but by definition weakness must present after the onset of critical illness. Currently, the overall occurrence of CIM is unknown because of non uniformity in studies of patient case mixes, diagnostic criteria used, and timing of evaluation for CIM.
Critical illness myopathy Signs and Symptoms
It is only during a systematic workup for generalized weakness and ventilatory failure in the critically ill patient that a diagnosis of CIM can be reached. A combination of electrophysiologic studies and histopathologic findings is required.
Criteria for the critical illness myopathy diagnosis include sensory nerve action potential amplitudes >80% of the lower limit of normal; needle electromyogram (EMG) with short-duration, low-amplitude motor unit potentials with early or normal full recruitment (with or without fibrillation potentials); absence of a decremental response on repetitive nerve stimulation; muscle biopsy findings of myopathy with myosin loss; and compound muscle action potential amplitudes <80% of the lower limit of normal in two or more nerves without conduction block.
Elevated serum creatinine kinase and demonstration of muscle inexcitability are also diagnostic features when taken together with the other findings. Further identification of the subtype of critical illness myopathy (thick filament myosin loss, rhabdomyolysis, necrotizing myopathy of intensive care, or cachectic myopathy) may aid in prognostication, since only necrotizing myopathy of intensive care is associated with a poor prognosis for return of muscle strength.
The definitive critical illness myopathy pathophysiology is still elusive, but most clinicians and scientists to date agree that the systemic inflammatory response syndrome (SIRS) accounts for the muscle organ failure, with CIM similar to other organ failures seen in patients with SIRS. This is due to the increased cytokine burden having a strong potential for mediating sepsis-induced proteolysis of myofibrillar proteins in muscle.
In addition to cytokine mediation, external factors can trigger the onset of critical illness myopathy, with the most important being high-dose glucocorticoids. Additionally, the protein degradation potency of steroids is increased by impaired neuromuscular transmission, which can be induced by surgical stress, drugs, or an underlying critical illness neuropathy.
Taken together, sepsis, steroids, and impaired neuromuscular transmission act synergistically to stimulate muscle proteolysis characteristic of CIM. The defined critical illness myopathy subtypes may therefore reflect the balance of proteolytic inputs in a dose-dependent manner, exposure-dependent manner, or both, and the severity of CIM may be controlled through limiting these inputs.
In terms of altering neuromuscular transmission, more than 50 drugs, notably neuromuscular blocking agents (i.e., pancuronium and vecuronium), aminoglycosides, clindamycin, and colistin cause pharmacologic muscle denervation.
In addition, denervation also causes a rise in glucocorticoid receptors in the cytosol of skeletal muscle resulting in increased sensitivity of muscle to steroids. Thus, the potential exists for a vicious cycle to develop when neuromuscular blockade, aminoglycosides, and steroids are administered simultaneously in the critically ill ICU patient.
There is no current critical illness myopathy treatment, although intensive physiotherapy seems promising. The current mainstay of critical illness myopathy management is directed at prevention through judicious use of drugs associated with the development of the myopathy.
It should be noted, however, that other mytotoxic factors responsible for producing myopathies in the critically ill have been identified, independent of sepsis or glucocorticoids or neuromuscular blocker administration. Most subtypes of CIM still carry a good prognosis for recovery of muscle strength over time, with the exception of necrotizing myopathy.
References
Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005;32: 140 and163.
Friedrich O, Fink RHA, Hund E. Understanding critical illness myopathy: approaching the pathomechanism. J Nutr 2005;135:181.
Latronico N, Peli E, Botteri M. Critical illness myopathy and neuropathy. Curr Opin Crit Care 2005;11:126
Latronico N, Shehu I, Seghelini E. Neuromuscular sequelae of critical illness. Curr Opin Crit Care 2005;11:381.