Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial

Angela S. McNelly; Danielle E. Bear; Bronwen A. Connolly; Gill Arbane; Laura Allum; Azhar Tarbhai; Jackie A. Cooper; Philip A. Hopkins; Matthew P. Wise; David Brealey; Kieron Rooney; Jason Cupitt; Bryan Carr; Kiran Koelfat; Steven Olde Damink; Philip J. Atherton; Nicholas Hart; Hugh E. Montgomery; Zudin A. Puthucheary

doi:10.1016/j.chest.2020.03.045

Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial

Angela S. McNelly^*, Danielle E. Bear, Bronwen A. Connolly, Gill Arbane, Laura Allum, Azhar Tarbhai, Jackie A. Cooper, Philip A. Hopkins, Matthew P. Wise, David Brealey, Kieron Rooney, Jason Cupitt, Bryan Carr, Kiran Koelfat, Steven Olde Damink, Philip J. Atherton, Nicholas Hart, Hugh E. Montgomery, Zudin A. Puthucheary

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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

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.

Original language	English
Pages (from-to)	183-194
Number of pages	12
Journal	Chest
Volume	158
Issue number	1
DOIs	https://doi.org/10.1016/j.chest.2020.03.045
Publication status	Published - Jul 2020

Keywords

critical care
energy delivery
muscle wasting
nutrition
protein delivery
UNIT-ACQUIRED WEAKNESS
HUMAN SKELETAL-MUSCLE
ILL PATIENTS
ENTERAL NUTRITION
PROTEIN-SYNTHESIS
CARE
THERAPY
TIME
REHABILITATION
SURVIVORS

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McNelly, A. S., Bear, D. E., Connolly, B. A., Arbane, G., Allum, L., Tarbhai, A., Cooper, J. A., Hopkins, P. A., Wise, M. P., Brealey, D., Rooney, K., Cupitt, J., Carr, B., Koelfat, K., Damink, S. O., Atherton, P. J., Hart, N., Montgomery, H. E., & Puthucheary, Z. A. (2020). Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial. Chest, 158(1), 183-194. https://doi.org/10.1016/j.chest.2020.03.045

@article{2ebc5884f37d44719fb11ad400bf9467,

title = "Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial",

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]; PINTERPRETATION: 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.",

keywords = "critical care, energy delivery, muscle wasting, nutrition, protein delivery, UNIT-ACQUIRED WEAKNESS, HUMAN SKELETAL-MUSCLE, ILL PATIENTS, ENTERAL NUTRITION, PROTEIN-SYNTHESIS, CARE, THERAPY, TIME, REHABILITATION, SURVIVORS",

author = "McNelly, {Angela S.} and Bear, {Danielle E.} and Connolly, {Bronwen A.} and Gill Arbane and Laura Allum and Azhar Tarbhai and Cooper, {Jackie A.} and Hopkins, {Philip A.} and Wise, {Matthew P.} and David Brealey and Kieron Rooney and Jason Cupitt and Bryan Carr and Kiran Koelfat and Damink, {Steven Olde} and Atherton, {Philip J.} and Nicholas Hart and Montgomery, {Hugh E.} and Puthucheary, {Zudin A.}",

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, Nestl{\'e} 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{\textquoteright}s and St Thomas{\textquoteright} 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{\textquoteright}s and St Thomas{\textquoteright} 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{\'e}, 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: {\textcopyright} 2020 American College of Chest Physicians",

year = "2020",

month = jul,

doi = "10.1016/j.chest.2020.03.045",

language = "English",

volume = "158",

pages = "183--194",

journal = "Chest",

issn = "0012-3692",

publisher = "Elsevier",

number = "1",

}

McNelly, AS, Bear, DE, Connolly, BA, Arbane, G, Allum, L, Tarbhai, A, Cooper, JA, Hopkins, PA, Wise, MP, Brealey, D, Rooney, K, Cupitt, J, Carr, B, Koelfat, K , Damink, SO, Atherton, PJ, Hart, N, Montgomery, HE & Puthucheary, ZA 2020, 'Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial', Chest, vol. 158, no. 1, pp. 183-194. https://doi.org/10.1016/j.chest.2020.03.045

TY - JOUR

T1 - Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness

T2 - A Phase 2 Clinical Trial

AU - McNelly, Angela S.

AU - Bear, Danielle E.

AU - Connolly, Bronwen A.

AU - Arbane, Gill

AU - Allum, Laura

AU - Tarbhai, Azhar

AU - Cooper, Jackie A.

AU - Hopkins, Philip A.

AU - Wise, Matthew P.

AU - Brealey, David

AU - Rooney, Kieron

AU - Cupitt, Jason

AU - Carr, Bryan

AU - Koelfat, Kiran

AU - Damink, Steven Olde

AU - Atherton, Philip J.

AU - Hart, Nicholas

AU - Montgomery, Hugh E.

AU - Puthucheary, Zudin A.

N1 - 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

PY - 2020/7

Y1 - 2020/7

N2 - 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]; PINTERPRETATION: 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.

AB - 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]; PINTERPRETATION: 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.

KW - critical care

KW - energy delivery

KW - muscle wasting

KW - nutrition

KW - protein delivery

KW - UNIT-ACQUIRED WEAKNESS

KW - HUMAN SKELETAL-MUSCLE

KW - ILL PATIENTS

KW - ENTERAL NUTRITION

KW - PROTEIN-SYNTHESIS

KW - CARE

KW - THERAPY

KW - TIME

KW - REHABILITATION

KW - SURVIVORS

U2 - 10.1016/j.chest.2020.03.045

DO - 10.1016/j.chest.2020.03.045

M3 - Article

C2 - 32247714

SN - 0012-3692

VL - 158

SP - 183

EP - 194

JO - Chest

JF - Chest

IS - 1

ER -