Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.
Details
Serval ID
serval:BIB_594EA1B9D9D1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.
Journal
Jpen. Journal of Parenteral and Enteral Nutrition
Working group(s)
Canadian Critical Care Trials Group
Contributor(s)
Muscedere J., Hammond C., Meyers M., Fleury S., O' Callaghan N., Cook D., McDonald E., Clarke F., Jones G., Watpool I., McArdle T., Porteous R., Pagliarello G., McArdle T., Chittock D., Gardner M., Logie S., Foster D., Albert M., Deroy P., Simard H., Ahern S., Harvey J., Magder S., Banici L., Kutsogiannis J., Thompson P., Scott K., Bartel R., Jossy D., Krawchuk C., Stollery D., Barchard J., Krause M., Wood G., Auld F., Atkins L., Martin C., Campbell E., Hall R., Julien L., Khwaja K., Banici L., Lauzier F., Gagne C., Thibodeault M., Wood G., Auld F., Leonard P., Atkins L., Mehta S., Brown M., Mele T., Bentall T., Lellouche F., Ferland MC., Meade M., Hand L., McDonald B., Winch D., Fowler R., Marinoff N., Dodek P., Ashley BJ., Wiebe K., Janz W., Wischmeyer P., Luzier E., Baer A., McCarthy M., Chowayou L., Garrett K., Allen F., Stapleton R., Martin J., Shea B., Saad M., DeSpirito C., Kosar R., Podbielski J., Vincent L., Morin K., Saad M., DeSpirito C., Dudick C., White J., Frankel H., Smith LA., White T., Kinikini M., Briggs B., Murray M., Watkins A., Berger M., Delodder F., Elke G., Weiler N., Schulz-Ruthenberg N., D' Aria S., Gründling M., Kuhn SO., Guderian L., Bause H., Gabriel P., Prause A., Wolf C., Spapen H., Opdenacker G., Preiser JC., Lefranq J.
ISSN
0148-6071 (Print)
ISSN-L
0148-6071
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
39
Number
4
Pages
401-409
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects.
MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification).
RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements.
CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.
MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification).
RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements.
CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.
Keywords
Aged, Antioxidants/adverse effects, Antioxidants/therapeutic use, Critical Illness/mortality, Critical Illness/therapy, Dietary Supplements/adverse effects, Glutamine/adverse effects, Glutamine/therapeutic use, Hospital Mortality, Humans, Kidney, Logistic Models, Middle Aged, Multiple Organ Failure/mortality, Multiple Organ Failure/therapy, Odds Ratio, Prospective Studies
Pubmed
Web of science
Create date
16/02/2015 10:43
Last modification date
20/08/2019 15:12
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