TY - JOUR AV - public VL - 14 Y1 - 2023/12/15/ TI - A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed IS - 1 N1 - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article?s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article?s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. PB - Springer Science and Business Media LLC UR - http://dx.doi.org/10.1038/s41467-023-42659-8 N2 - 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. ID - discovery10184236 A1 - McNelly, Angela A1 - Langan, Anne A1 - Bear, Danielle E A1 - Page, Alexandria A1 - Martin, Tim A1 - Seidu, Fatima A1 - Santos, Filipa A1 - Rooney, Kieron A1 - Liang, Kaifeng A1 - Heales, Simon J A1 - Baldwin, Tomas A1 - Alldritt, Isabelle A1 - Crossland, Hannah A1 - Atherton, Philip J A1 - Wilkinson, Daniel A1 - Montgomery, Hugh A1 - Prowle, John A1 - Pearse, Rupert A1 - Eaton, Simon A1 - Puthucheary, Zudin A KW - Drug development KW - Phase I trials KW - Translational research JF - Nature Communications ER -