Changes in Skeletal Muscle Mass and Contractile Function

Abstract

Intensive Care Unit Acquired Weakness, a well recognized complication of critical illness, is caused by dysfunction of the neural axis and/or skeletal muscle. It increases ICU and hospital mortality and in the ICU survivor is associated with sustained physical disability, substantially increased health resource utilization and health care costs. To date, there is no intervention that can universally and consistently prevent weakness during critical illness, or enhance its recovery following ICU discharge to improve physical function. The pathophysiology of ICUAW is complex and heterogeneous. This chapter focuses on our current understanding of the pathophysiology driving critical illness myopathy. It reviews the biology behind skeletal muscle loss and dysfunction that occurs in the ICU and can persist in the critical illness survivor. Muscle wasting is a multifactorial process induced by increased muscle proteolysis and decreased protein synthesis in the early phase of critical illness, and the cellular processes and molecular signaling networks responsible will be discussed. Similarly, the biologic processes underpinning impaired muscle contractility are highlighted. The durable impact of critical illness on skeletal muscle biology and the mechanisms resulting in sustained muscle wasting following ICU discharge are also discussed. Current and potential future therapeutic approaches to the prevention and treatment of muscle dysfunction in critical illness and after illness resolution, are proposed.