Cited by 71Muscle metabolism and nutritionClinical Nutrition and GastroenterologyIntensive Care Unit Cognitive Disorders

An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers

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Gamrin-Gripenberg, Lena, Sundström-Rehal, Martin, Olsson, Daniel, Grip, Jonathan, Wernerman, Jan, Rooyackers, Olav·2018·Critical Care

Abstract

BACKGROUND: There is extensive documentation on skeletal muscle protein depletion during the initial phase of critical illness. However, for intensive care unit (ICU) long-stayers, objective data are very limited. In this study, we examined skeletal muscle protein and amino acid turnover in patients with a prolonged ICU stay. METHODS: Patients (n = 20) were studied serially every 8-12 days between days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg muscle protein turnover was assessed by measurements of phenylalanine kinetics, for which we employed a stable isotope-labeled phenylalanine together with two-pool and three-pool models for calculations, and results were expressed per 100 ml of leg volume. In addition, leg muscle amino acid flux was studied. RESULTS: The negative leg muscle protein net balance seen on days 10-20 of the ICU stay disappeared by days 30-40 (p = 0.012). This was attributable mainly to an increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by an attenuated efflux of free amino acids from the leg. Leg muscle protein breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3-methylhistidine. The arterial plasma concentrations of free amino acids did not change over the course of the study. CONCLUSIONS: In critically ill patients with sustained organ failure and in need of a prolonged ICU stay, the initial high rate of skeletal muscle protein depletion was attenuated over time. The distinction between the acute phase and a more prolonged and more stable phase concerning skeletal muscle protein turnover must be considered in study protocols as well as in clinical practice. TRIAL REGISTRATION: Australian New Zealand Trial Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016.

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Crossref · 10.1186/s13054-017-1932-6

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  • Recent stable isotope studies demonstrate that amino acid conversion is improved with time, allowing an increase in whole body protein production only after the early period of the acute phase, even increasing further in the post-acute phase.

    “Recent stable isotope studies [63,64] demonstrate that amino acid conversion is improved with time, allowing an increase in whole body protein production only after the early period of the acute phase, even increasing further in the post-acute phase.”

    From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [63]

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  1. [1]Walsh CJ Batt J Herridge MS Dos Santos CC Muscle wasting and early mobilization in acute respiratory distress syndrome Clin Chest Med 2014 35 4 811 26 10.1016/j.ccm.2014.08.016 25453427 · DOI
  2. [2]Dos Santos C Hussain SN Mathur S Picard M Herridge M Correa J Bain A Guo Y Advani A Advani SL Mechanisms of chronic muscle wasting and dysfunction after an intensive care unit stay: a pilot study Am J Respir Crit Care Med 2016 194 7 821 30 10.1164/rccm.201512-2344OC 27058306 · DOI
  3. [3]Casaer MP Muscle weakness and nutrition therapy in ICU Curr Opin Clin Nutr Metab Care 2015 18 2 162 8 10.1097/MCO.0000000000000150 25603227 · DOI
  4. [4]Casaer MP Langouche L Coudyzer W Vanbeckevoort D De Dobbelaer B Guiza FG Wouters PJ Mesotten D Van den Berghe G Impact of early parenteral nutrition on muscle and adipose tissue compartments during critical illness Crit Care Med 2013 41 10 2298 309 10.1097/CCM.0b013e31828cef02 23860247 · DOI
  5. [5]Gamrin L Andersson K Hultman E Nilsson E Essen P Wernerman J Longitudinal changes of biochemical parameters in muscle during critical illness Metabolism 1997 46 7 756 62 10.1016/S0026-0495(97)90119-0 9225828 · DOI
  6. [6]Gamrin L Essen P Forsberg AM Hultman E Wernerman J A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids, energy-rich phosphates, protein, nucleic acids, fat, water, and electrolytes Crit Care Med 1996 24 4 575 83 10.1097/00003246-199604000-00005 8612406 · DOI
  7. [7]Puthucheary ZA Rawal J McPhail M Connolly B Ratnayake G Chan P Hopkinson NS Padhke R Dew T Sidhu PS Acute skeletal muscle wasting in critical illness JAMA 2013 310 15 1591 600 10.1001/jama.2013.278481 24108501 · DOI · Paper page
  8. [8]Reid CL Campbell IT Little RA Muscle wasting and energy balance in critical illness Clin Nutr 2004 23 2 273 80 10.1016/S0261-5614(03)00129-8 15030968 · DOI
  9. [9]Biolo G Bosutti A Iscra F Toigo G Gullo A Guarnieri G Contribution of the ubiquitin-proteasome pathway to overall muscle proteolysis in hypercatabolic patients Metab Clin Exp 2000 49 6 689 91 10.1053/meta.2000.6236 10877190 · DOI
  10. [12]Klaude M Mori M Tjader I Gustafsson T Wernerman J Rooyackers O Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis Clin Sci 2012 122 3 133 42 10.1042/CS20110233 21880013 · DOI
  11. [14]Essén P McNurlan MA Gamrin L Hunter K Calder G Garlick PJ Wernerman J Tissue protein synthesis rates in critically ill patients Crit Care Med 1998 26 1 92 100 10.1097/00003246-199801000-00022 9428549 · DOI
  12. [15]Gamrin L Essén P Hultman E McNurlan MA Garlick PJ Wernerman J Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients Ann Surg 2000 231 4 577 86 10.1097/00000658-200004000-00018 10749620 PMC1421035 · DOI
  13. [16]Tjader I Rooyackers O Forsberg AM Vesali RF Garlick PJ Wernerman J Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients Intensive Care Med 2004 30 2 266 75 10.1007/s00134-003-2048-9 14722645 · DOI
  14. [17]Vesali RF Klaude M Rooyackers OE Tjäder I Barle H Wernerman J Longitudinal pattern of glutamine/glutamate balance across the leg in long-stay intensive care unit patients Clin Nutr 2002 21 6 505 14 10.1054/clnu.2002.0583 12468371 · DOI
  15. [18]Vesali RF Klaude M Thunblad L Rooyackers OE Wernerman J Contractile protein breakdown in human leg skeletal muscle as estimated by [2H3]-3-methylhistidine: a new method Metab Clin Exp 2004 53 8 1076 80 10.1016/j.metabol.2004.02.017 15281022 · DOI
  16. [19]Fitzmaurice GM Laird NM Ware JH Applied longitudinal analysis 2012 2 Hoboken Wiley
  17. [21]Caso G Garlick PJ Ballou LM Vosswinkel JA Gelato MC McNurlan MA The increase in human muscle protein synthesis induced by food intake is similar when assessed with the constant infusion and flooding techniques J Nutr 2006 136 6 1504 10 10.1093/jn/136.6.1504 16702312 · DOI
  18. [22]Gruther W Benesch T Zorn C Paternostro-Sluga T Quittan M Fialka-Moser V Spiss C Kainberger F Crevenna R Muscle wasting in intensive care patients: ultrasound observation of the M. quadriceps femoris muscle layer J Rehabil Med 2008 40 3 185 9 10.2340/16501977-0139 18292919 · DOI · Paper page

Cited by

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Authors
Gamrin-Gripenberg, L., Sundström-Rehal, M., Olsson, D., Grip, J., Wernerman, J., & Rooyackers, O.
Affiliations
  • Karolinska Institutet (SE)
  • Karolinska University Hospital (SE)
Corresponding author
Rooyackers, Olav
Venue
Critical Care
Published
2018-01-23
Volume
22
Issue
1
Pages
13-13
ISSN
1364-8535 (ISSN-L)
OpenAlex
W2792457722
Cited by
71
References
1
Citations by year
2026: 5 · 2025: 13 · 2024: 12 · 2023: 6 · 2022: 10 · 2021: 6 · 2020: 11 · 2019: 4 · 2018: 4
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Critical Care (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Stockholms Läns Landsting
  • Vetenskapsrådet
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Keywords
skeletal muscle protein turnover, phenylalanine kinetics, de novo protein synthesis, muscle protein degradation, 3-methylhistidine, prolonged ICU stay, critical illness, muscle atrophy, organ failure
MeSH terms
Aged, Amino Acids, Female, Humans, Intensive Care Units, Leg, Length of Stay, Male, Middle Aged, Muscle Proteins, Phenylalanine, Sweden, Time Factors, Muscle, Skeletal

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