Impaired muscle metabolism in the ICU: interrogating the underlying pathophysiology

Purpose of review Accelerated muscle wasting in critically ill patients contributes to poor recovery outcomes. Critical care guidelines recommend delivering higher protein doses; yet, increasing evidence suggests harm from higher protein doses. Recent findings Definitive randomised controlled trials in critically ill adults have reported signals of harm from higher protein administration compared to lower protein doses or standard of care, with significant results pertaining to reduced health-related quality of life and worse outcomes in sub-groups of acute kidney injury and higher illness severity. Physiological data demonstrate anabolic resistance to dietary protein and elevated rates of protein degradation. Recent human studies propose novel mechanisms to explain these results, including inflammation, apoptosis, and deranged concentrations of vitamin D and intramuscular zinc. Preclinical models may elucidate mechanisms core to muscle wasting: ‘micro muscles’ cell culture systems can assess muscle loss in response to nutrient administration; and both rodent and large animal models allow for mechanistic interrogation of muscle metabolism in response to feeding. Summary Higher protein doses alone are unlikely to attenuate muscle wasting. Understanding mechanisms for anabolic resistance and increased protein degradation, employing preclinical models, will support the development of targeted strategies to prevent muscle loss during critical illness.