Angela S McNelly1, Danielle E Bear2, Bronwen A Connolly3, Gill Arbane4, Laura Allum4, Azhar Tarbhai5, Jackie A Cooper5, Philip A Hopkins6, Matthew P Wise7, David Brealey8, Kieron Rooney9, Jason Cupitt10, Bryan Carr11, Kiran Koelfat12, Steven Olde Damink13, Philip J Atherton14, Nicholas Hart4, Hugh E Montgomery15, Zudin A Puthucheary16. 1. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; University College London (UCL), London, United Kingdom; National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at UCL Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address: angela.mcnelly@qmul.ac.uk. 2. Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; Department of Critical Care, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; NIHR BRC, King's College London, London, United Kingdom. 3. NIHR BRC, King's College London, London, United Kingdom; Lane Fox Clinical Respiratory Physiology Research Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 4. Lane Fox Clinical Respiratory Physiology Research Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 5. University College London (UCL), London, United Kingdom. 6. Kings College Hospital, London, United Kingdom. 7. University Hospital of Wales, Cardiff, Wales, United Kingdom. 8. National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at UCL Hospitals NHS Foundation Trust, London, United Kingdom. 9. Bristol Royal Infirmary, Bristol, United Kingdom. 10. Blackpool Victoria Hospital, Blackpool, United Kingdom. 11. University Hospitals of North Midlands, Stoke-on-Trent, United Kingdom. 12. Department of Surgery and School of Nutrition and Translational Research in Metabolism (NUTRIM), University of Maastricht, Maastricht, The Netherlands. 13. Department of Surgery and School of Nutrition and Translational Research in Metabolism (NUTRIM), University of Maastricht, Maastricht, The Netherlands; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany. 14. Medical Research Council/Arthritis Research UK Centre for Musculoskeletal Aging, University of Nottingham, Nottingham, United Kingdom. 15. University College London (UCL), London, United Kingdom; National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at UCL Hospitals NHS Foundation Trust, London, United Kingdom. 16. Adult Critical Care Unit, Royal London Hospital, London, United Kingdom; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Abstract
BACKGROUND: Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality. Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding, which may ameliorate it. RESEARCH QUESTION: Does intermittent enteral feed decrease muscle wasting compared with continuous feed in critically ill patients? STUDY DESIGN AND METHODS: In a phase 2 interventional single-blinded randomized controlled trial, 121 mechanically ventilated adult patients with multiorgan failure were recruited following prospective informed consultee assent. They were randomized to the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 h, n = 62) or control group (standard continuous enteral feeding, n = 59). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, glycemic control, and physical function milestones. RESULTS:Muscle loss was similar between arms (-1.1% [95% CI, -6.1% to -4.0%]; P = .676). More intermittently fed patients received 80% or more of target protein (OR, 1.52 [1.16-1.99]; P < .001) and energy (OR, 1.59 [1.21-2.08]; P = .001). Plasma branched-chain amino acid concentrations before and after feeds were similar between arms on trial day 1 (71 μM [44-98 μM]; P = .547) and trial day 10 (239 μM [33-444 μM]; P = .178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6-20.4]) vs continuous feed (12.98 [14.0-15.7]; P < .001). However, days with reported hypoglycemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups. INTERPRETATION: Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality. Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding, which may ameliorate it. RESEARCH QUESTION: Does intermittent enteral feed decrease muscle wasting compared with continuous feed in critically illpatients? STUDY DESIGN AND METHODS: In a phase 2 interventional single-blinded randomized controlled trial, 121 mechanically ventilated adult patients with multiorgan failure were recruited following prospective informed consultee assent. They were randomized to the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 h, n = 62) or control group (standard continuous enteral feeding, n = 59). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, glycemic control, and physical function milestones. RESULTS: Muscle loss was similar between arms (-1.1% [95% CI, -6.1% to -4.0%]; P = .676). More intermittently fed patients received 80% or more of target protein (OR, 1.52 [1.16-1.99]; P < .001) and energy (OR, 1.59 [1.21-2.08]; P = .001). Plasma branched-chain amino acid concentrations before and after feeds were similar between arms on trial day 1 (71 μM [44-98 μM]; P = .547) and trial day 10 (239 μM [33-444 μM]; P = .178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6-20.4]) vs continuous feed (12.98 [14.0-15.7]; P < .001). However, days with reported hypoglycemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups. INTERPRETATION: Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov.
Authors: Emma J Ridley; Michael Bailey; Marianne Chapman; Lee-Anne S Chapple; Adam M Deane; Carol Hodgson; Victoria L King; Andrea Marshall; Eliza G Miller; S P McGuinness; Rachael Parke; Andrew A Udy Journal: BMJ Open Date: 2022-03-08 Impact factor: 2.692
Authors: Kirby P Mayer; Melissa L Thompson Bastin; Ashley A Montgomery-Yates; Amy M Pastva; Esther E Dupont-Versteegden; Selina M Parry; Peter E Morris Journal: Crit Care Date: 2020-11-04 Impact factor: 9.097
Authors: Kym Wittholz; Kate Fetterplace; Yasmine Ali Abdelhamid; Jeffrey J Presneill; Lisa Beach; Benjamin Thomson; David Read; René Koopman; Adam M Deane Journal: Pilot Feasibility Stud Date: 2022-01-31