Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial
- PMID: 24803474
- PMCID: PMC6800175
- DOI: 10.1177/0148607114529994
Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial
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.
Trial registration: ClinicalTrials.gov NCT00133978.
Keywords: antioxidants; critical care; glutamine; post hoc analysis; randomized clinical trials.
© 2014 American Society for Parenteral and Enteral Nutrition.
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References
-
- Motoyama T, Okamoto K, Kukita I, Hamaguchi M, Kinoshita Y, Ogawa H. Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome. Crit Care Med. 2003;31: 1048–1052. - PubMed
-
- Alonso de Vega JM, Díaz J, Serrano E, Carbonell LF. Oxidative stress in critically ill patients with systemic inflammatory response syndrome. Crit Care Med. 2002;30:1782–1786. - PubMed
-
- Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med. 1995;23:646–651. - PubMed
-
- Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002;360:219–223. - PubMed
-
- Goodyear-Bruch C, Pierce JD. Oxidative stress in critically ill patients. Am J Crit Care. 2002;11:543–561. - PubMed
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