Alternative Substrates in the Critically Ill Subject (ASICS): Safety, Feasibility, Tolerability and Metabolic Profiling of a Novel Ketogenic Feed

Bioenergetic failure caused by impaired utilisation of glucose and fatty acids contributes to organ dysfunction across multiple tissues in critical illness. Ketone bodies may form an alternative substrate source, but the feasibility and safety of inducing a ketogenic state in physiologically unstable patients is not known. Twenty-nine mechanically ventilated adults with multi-organ failure were randomised into a two-centre safety and feasibility trial of ketogenic versus standard enteral feeding. Ketogenic feeding was feasible, safe, well tolerated and resulted in ketosis. Patients receiving ketogenic feeding had fewer hypoglycaemic events (0% vs. 1.58%), required less exogenous insulin (0.0 IU (IQR 0-16) vs.78 IU (IQR 0-412) but had slightly more daily episodes of diarrhoea (53.5% vs. 42.9%) over the trial period. Untargeted metabophenotyping revealed altered Cahill cycle flux and bioenergetic states, suggesting an advantageous metabolic profile. Ketogenic feeding is feasible and may be a novel intervention for addressing bioenergetic failure in critically ill patients. Clinical Trials.gov registration: NCT04101071; 19.09.2019. Take-home MessageCritical illness leads to altered metabolic states and bioenergetic failure caused by impaired utilisation of glucose, fatty acids and amino acids. This contributes to organ dysfunction across multiple tissues. Ketones may provide a safe and acceptable alternative metabolic fuel enabling energy production and maintaining tissue homeostasis. TweetKetogenic enteral feeding in early critical illness is feasible, safe and may decrease insulin requirements.