Molecular mechanisms of intensive care unit-acquired weakness

Abstract

Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology. Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure. As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.