Mechanism of ICU-acquired weakness: muscle contractility in critical illness

Excerpt

Weakness is common after an episode of critical illness and its associated disability may persist for years, with significant negative impact on the survivor [1]. Strength depends on both the presence and normal function of skeletal muscle, so that either muscle wasting or impaired contractility (muscle-specific force) can induce weakness. This is best appreciated in the gerontology literature where sarcopenia, the concept of which has evolved from simple muscle wasting to loss of muscle mass and function, and dynapenia (loss of strength and power not necessarily associated with loss of muscle mass) are identified and considered separately because they are not synonymous [2]. In aging, the decline in strength exceeds the loss of muscle mass and this is attributed to changes throughout the neuroaxis including those occurring at the peripheral nerve in addition to muscle. Muscle unloading/inactivity in animal models promotes a loss of contractile proteins that exceeds the loss in muscle cell size, resulting in decreased myocyte-specific force [3] and in young adults muscle atrophied by immobilization may recover to regain mass but not strength, reinforcing the notion that, like the dynapenia of aging, muscle strength and mass may be discordant. A pilot study of critical illness-associated weakness also suggests this holds true [4]. Therefore, studies evaluating ICU-acquired weakness (ICUAW) should ensure complete assessment for peripheral neuropathy, neuromuscular junction dysfunction in addition to evaluation for myopathy—loss of muscle mass and deficiency of intrinsic contractility. Although the clinical phenotype may be weakness, the relative contributions of underlying processes and cellular and molecular mechanisms may be very different. This review will focus on the impairment of muscle contractility in critical illness and discuss the responsible muscle-derived cellular and molecular mechanisms. …