Should nutrition therapy be modified to account for mitochondrial dysfunction in critical illness?

Metabolic dysfunction, and its associated muscle atrophy, remains the most common complication of critical care. At the center of this is mitochondrial dysfunction, secondary to hypoxia and systemic inflammation. This leads to a bioenergetic crisis, with decreased intramuscular adenosine triphosphate content and a reduction in the highly energy-dependent process of protein synthesis. Numerous methods have been studied to try and reduce these effects, with only limited success. Trials investigating the use of increased energy and protein administration have instead found a decrease in relative lean body mass and a potential increase in morbidity and mortality. Ketone bodies have been proposed as alternative substrates for metabolism in critical illness, with promising results seen in animal models. They are currently being investigated in critical care patients in the Alternative Substrates in the Critically Ill Subjects trial (ASICS). The evidence to date suggests that individualized feeding regimens may be key in the nutrition approach to critical illness. Consideration of individual patient factors will need to be combined with personalized protein content, total energy load received, and the timing of such feeds. This review covers mitochondrial dysfunction in critical illness, how it contributes to muscle wasting and the resultant morbidity and mortality, and the scientific basis of why current nutrition approaches to date have not been successful in negating this effect. These two factors underpin the need for consideration of alternative nutrition strategies in the critically ill patient.