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
Original language | English |
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Pages (from-to) | 183-194 |
Number of pages | 12 |
Journal | Chest |
Volume | 158 |
Issue number | 1 |
DOIs | |
Publication status | Published - 01 Jul 2020 |
Externally published | Yes |
Bibliographical note
Funding Information:FUNDING/SUPPORT: J P Moulton Charitable Foundation (JM29/04/14; JM02/06/15); NIHR UCL/UCLH BRC cardiometabolic research grant (BRC202 rev/CM/AM/101320; RCF236/AMcN/2015); Intensive Care Foundation (New Investigator Award, A. S. McN.); London South Local Clinical Research Network (LCRN) (D. E. B.: November 2014-May 2015); North Thames LCRN (A. S. McN.: January 2017-March 2017); ASPEN Rhoads Research Foundation (Z. A. P.: January 2018-January 2020).
Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. E. B. reports speaker fees from Nutricia, Baxter Healthcare, B. Braun, and Fresenius Kabi; advisory board fees from Baxter Healthcare, Nestlé Nutrition, Fresenius Kabi, Abbott Nutrition, Cardinal Health, and Avanos; and conference attendance support from B. Braun, outside the submitted work. 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, Fresenius Kabi, Nestlé, Orion, and GlaxoSmithKline, outside the submitted work. None declared (A. S. McN., B. A. C., G. A., L. A., A. T., J. A. C., P. A. H., M. P. W., D. B., K. R., J. C., B. C., K. K., S. O. D., P. J. A.).
Funding Information:
Author contributions: A. S. McN. D. E. B. B. A. C. P. J. A. N. H. H. E. M. and Z. A. P. made substantial contributions to the conception or design of the work; A. S. McN. D. E. B. G. A. L. A. A. T. P. A. H. M. P. W. D. B. K. R. J. C. B. C. and K. K. acquired the data; A. S. McN. D. E. B. J. A. C. P. J. A. S. O. D. and Z. A. P. analyzed or interpreted the data; all authors drafted the work or revised it critically for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Z. A. P. takes responsibility for the content of the manuscript, including the data and analysis. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. E. B. reports speaker fees from Nutricia, Baxter Healthcare, B. Braun, and Fresenius Kabi; advisory board fees from Baxter Healthcare, Nestl? Nutrition, Fresenius Kabi, Abbott Nutrition, Cardinal Health, and Avanos; and conference attendance support from B. Braun, outside the submitted work. 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, Fresenius Kabi, Nestl?, Orion, and GlaxoSmithKline, outside the submitted work. None declared (A. S. McN. B. A. C. G. A. L. A. A. T. J. A. C. P. A. H. M. P. W. D. B. K. R. J. C. B. C. K. K. S. O. D. P. J. A.). Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Other contributions: The authors thank the patients (and their families) who took part, and the staff of all recruiting centers, for their willingness to engage. The following persons made substantive contributions to the study: Sheik Pahary, Rebecca Youngman, Kanakraj Roberts, Ian Taylor, Rebecca Oettle, Beth Penhalighan, Clair-Louise Harris, Clare Donegan, Paul Riozzi, Leah Thompson, Harriet Noble, John Smith, Jade M. Cole, Matt P. G. Morgan, Helen Hill, Eve Cocks, Jenny Brooks, Paul Twose, Erica Thornton, Rhys Davies, Christopher Whitton, Nicki Palmer, Jacqueline Curtin, Amelia Jones, Jo Jefford, Chloe Nottingham, Naomi Ronan, Denise Webster, Lisa Grimmer, Chloe Allison, Kate Driver, Jennifer Bennett-Britton, Libby Cole, Emma Stoddard, Carol Jeffs, Michael Gater, Minerva Gellamucho, Colin Emm, Caoihme Dempsey, Samantha Cook, Nagesh Bandla, Nehal Patel, and Hans van Eijk. Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article.
Publisher Copyright:
© 2020 American College of Chest Physicians
Keywords
- critical care
- energy delivery
- muscle wasting
- nutrition
- protein delivery
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine