Nature Communications (Dec 2023)

A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed

  • Angela McNelly,
  • Anne Langan,
  • Danielle E. Bear,
  • Alexandria Page,
  • Tim Martin,
  • Fatima Seidu,
  • Filipa Santos,
  • Kieron Rooney,
  • Kaifeng Liang,
  • Simon J. Heales,
  • Tomas Baldwin,
  • Isabelle Alldritt,
  • Hannah Crossland,
  • Philip J. Atherton,
  • Daniel Wilkinson,
  • Hugh Montgomery,
  • John Prowle,
  • Rupert Pearse,
  • Simon Eaton,
  • Zudin A. Puthucheary

DOI
https://doi.org/10.1038/s41467-023-42659-8
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 14

Abstract

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Abstract 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 managed on intensive care units were randomised (Ketogenic n = 14, Control n = 15) into a two-centre pilot open-label trial of ketogenic versus standard enteral feeding. The primary endpoints were assessment of feasibility and safety, recruitment and retention rates and achievement of ketosis and glucose control. Ketogenic feeding was feasible, safe, well tolerated and resulted in ketosis in all patients in the intervention group, with a refusal rate of 4.1% and 82.8% retention. Patients who received ketogenic feeding had fewer hypoglycaemic events (0.0% vs. 1.6%), required less exogenous international units of insulin (0 (Interquartile range 0-16) vs.78 (Interquartile range 0-412) but had slightly more daily episodes of diarrhoea (53.5% vs. 42.9%) over the trial period. Ketogenic feeding was feasible and may be an intervention for addressing bioenergetic failure in critically ill patients. Clinical Trials.gov registration: NCT04101071.