Introduction
muscle mass, death, critically ill, hypoxia, Ketoacidosis, acidosis, ketosis, Critically ill, Critical illness, vital organ dysfunction, multi-organ failure
PHYSIOLOGICAL STRESS, HYPOGLYCAEMIA, CRITICALLY ILL, HYPOXIA, INFLAMMATION, KETOACIDOSIS, ACIDOSIS, KETOSIS, CRITICALLY ILL, CRITICAL ILLNESS, CRITICAL ILLNESS, MULTI-ORGAN FAILURE, MUSCLE WASTING
Critical illness is a state of ill health with vital organ dysfunction and a high risk of imminent death if care (pharmacological or mechanical) is not provided and has the potential for reversibilityHepatic metabolism of fatty acids can yield ketone bodies such as beta-hydroxybutyrate and acetoacetate. Under conditions of physiological stress, these act as substrates for Adenosine Triphosphate (ATP) generation in the mitochondria of extra-hepatic tissues. In high intensity exercise, ketogenic diets provide ketone body substrates, improving ATP production, decreasing muscle protein breakdown and improving physical performance.Ketolysis occurs in mitochondria of extra-hepatic tissues, resulting in the formation of acetyl-CoA. The rate-determining step is the reconstitution of acetoacetyl-CoA from acetoacetate by the enzyme succinyl CoA-oxoacid transferase, which is not regulated by hypoxia or inflammation, unlike pyruvate dehydrogenase kinaseOne specific physiological consequence of critical illness that may be attenuated by a ketogenic diet is that of muscle wasting. Critically ill patients lose 2–3% of their muscle mass per dayHowever, the feasibility and safety of achieving ketosis in unstable patients in multi-organ failure has yet to be proven. Ketoacidosis might occur if ketones were not metabolised, exacerbating pre-existing systemic and cellular acidosis that carries a mortality risk to critically ill patients. Ketogenic diets minimise exogenous glucose delivery, which might predispose patients to hypoglycaemia, which is harmful to patientsWe therefore performed a randomised trial to determine the feasibility and safety of delivering a ketogenic enteral feed in critically ill patients and collecting physical function-specific outcomes. We additionally performed an exploratory analysis of plasma metabolomic profiling to ascertain the presence or absence of a signal for efficacy in altering tissue metabolism, which might warrant further research in a larger trial.