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Glutamine and Antioxidants in the Critically Ill Patient
Author(s) -
Heyland Daren K.,
Elke Gunnar,
Cook Deborah,
Berger Mette M.,
Wischmeyer Paul E.,
Albert Martin,
Muscedere John,
Jones Gwynne,
Day Andrew G.
Publication year - 2015
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607114529994
Subject(s) - glutamine , placebo , medicine , post hoc analysis , subgroup analysis , randomized controlled trial , confidence interval , odds ratio , biology , biochemistry , pathology , alternative medicine , amino acid
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.