The metabolic effects of intermittent versus continuous feeding in critically ill patients

Wilkinson, D.; Gallagher, I. J.; McNelly, A.; Bear, D. E.; Hart, N.; Montgomery, H. E.; Le Guennec, A.; Conte, M. R.; Francis, T.; Harridge, S. D. R.; Atherton, P. J.; Puthucheary, Z. A.

Abstract

Intermittent (or bolus) feeding regimens in critically ill patients have been of increasing interest to clinicians and scientists. Changes in amino acid, fat and carbohydrate metabolites over time might yet deliver other benefits (e.g. modulation of the circadian rhythm and sleep, and impacts on ghrelin secretion, insulin resistance and autophagy). We set out to characterise these changes in metabolite concentration. The Intermittent versus Continuous Feeding in Critically Ill paitents study (NCT02358512) was an eight-centre single-blinded randomised controlled trial. Patients were randomised to received a continuous (control arm) or intermittent (6x/day, intervention arm) enteral feeding regimen. Blood samples were taken on trial days 1, 7 and 10 immediately before and 30 min after intermittent feeds, and at equivalent timepoints in the control arm. A pre-planned targeted metabolomic analysis was performend using Nuclear Resonance Spectroscopy. Five hundred and ninety four samples were analysed from 75 patients. A total of 24 amino acid-, 19 lipid based-, and 44 small molecule metabolite features. Across the main two axes of variation (40–60% and 6–8% of variance), no broad patterns distinguished between intermittent or continuous feeding arms, across intra-day sampling times or over the 10 days from initial ICU admission. Logfold decreases in abundance were seen in metabolites related to amino acids (Glutamine − 0.682; Alanine − 0.594), ketone body metabolism (Acetone − 0.64; 3-Hydroxybutyric Acid − 0.632; Acetonacetic Acid − 0.586), fatty acid (carnitine − 0.509) and carbohydrate metabolism (Maltose − 0.510; Citric Acid − 0.485). 2–3 Butanediol, a by-product of sugar-fermenting microbial metabolism also decreased (− 0.489). No correlation was seen with change in quadriceps muscle mass for any of the 20 metabolites varying with time (all p > 0.05). Increasing severity of organ failure was related to increasing ketone body metabolism (3 Hydroxybutyric Acid-1 and − 3; p = 0.056 and p = 0.014), carnitine deficiency (p = 0.002) and alanine abundancy (p − 0.005). A 6-times a day intermittent feeding regimen did not alter metabolite patterns across time compared to continuous feeding in critically ill patients, either within a 24 h period or across 10 days of intervention. Future research on intermittent feeding regimens should focus on clinical process benefits, or extended gut rest and fasting.

Citation

Wilkinson, D., Gallagher, I. J., McNelly, A., Bear, D. E., Hart, N., Montgomery, H. E., …Puthucheary, Z. A. (2023). The metabolic effects of intermittent versus continuous feeding in critically ill patients. Scientific Reports, 13(1), Article 19508. https://doi.org/10.1038/s41598-023-46490-5

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2023
• Online Publication Date: Nov 9, 2023
• Publication Date: 2023
• Deposit Date: Jan 18, 2024
• Publicly Available Date: Jan 18, 2024
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 19508
• DOI: https://doi.org/10.1038/s41598-023-46490-5
• Keywords: Clinical trial design; Translational research
• Public URL: https://nottingham-repository.worktribe.com/output/27364501
• Publisher URL: https://www.nature.com/articles/s41598-023-46490-5
• Additional Information: Received: 15 April 2023; Accepted: 1 November 2023; First Online: 9 November 2023; : This work was supported (in part) by the ASPEN Rhoads Research Foundation. D. E. B. reports speaker fees from, Baxter Healthcare; advisory board fees from Baxter Healthcare;. N. H. reports unrestricted grants from Philips and ResMed outside the direct area of work commented on here with the funds held and managed by Guy’s and St Thomas’ NHS Foundation Trust; financial support from Philips for the development of MYOTRACE technology that has a patent filed in Europe (US pending) outside the area of work commented on here; personal fees for lecturing from Philips-Respironics, Philips, ResMed, and Fisher-Paykel both within and outside the area of work commented on here; N. H. is on the Pulmonary Research Advisory Board for Philips outside the area of work commented on here with the funds for this role held by Guy’s and St Thomas’ NHS Foundation Trust. H. E. M. has a patent, “The Use of Inhibitors of the Renin-Angiotensin System,” which relates in part to the prevention of muscle wasting, issued. Z. A. P. reports personal fees from Faraday Pharmaceuticals, Lyric Pharmaceuticals,Bioage, Fresenius Kabi, Nestlé, Orion, and GlaxoSmithKline, outside the submitted work. None declared (DW, IJG, AM,PJA, ALG, MRC, TF, SDR).