A randomized trial of glutamine and antioxidants in critically ill patients.

Randomized, multicenter, factorial trial in critically ill adults with multiorgan failure requiring mechanical ventilation. Active intervention arms included glutamine (N=301), antioxidants (N=307), and antioxidants plus glutamine (N=310); participants were enrolled from 40 ICUs in Canada, the United States, and Europe between April 2005 and December 2011.

This 2x2 factorial trial tested early nutritional supplementation with glutamine, antioxidants, or both, compared with matched placebo. Glutamine was given intravenously at 0.35 g/kg/day by ideal body weight as alanyl-glutamine (0.50 g/kg/day) and enterally as 42.5 g/day of alanyl-glutamine and glycine-glutamine dipeptides providing 30 g of glutamine per day, for up to 28 days or until ICU discharge or death. The antioxidant regimen consisted of 500 μg selenium intravenously plus enteral selenium 300 μg, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg, also continued for up to 28 days or until discharge or death.

Early supplementation did not improve outcomes overall, and glutamine was associated with worse survival. For 28-day mortality, glutamine increased death versus no glutamine (32.4% vs 27.2%; adjusted odds ratio 1.28, 95% CI 1.00 to 1.64; P = 0.05), while antioxidants had no significant effect (30.8% vs 28.8%; adjusted odds ratio 1.09, 95% CI 0.86 to 1.40; P = 0.48). In-hospital mortality and 6-month mortality were also significantly higher among patients who received glutamine. Serious adverse events occurred in 52 cases among 46 patients, with 4 considered potentially related to study supplements.

Complex factorial design with multiple active regimens makes isolated attribution less straightforward, and the excerpt provides limited arm-specific detail for secondary outcomes. Adherence was incomplete overall, with only 70.9% of enteral and 89.1% of parenteral study supplements reportedly received, and the trial spanned multiple countries and ICUs, which may increase heterogeneity. Ethnicity, physical activity, and arm-specific dietary intake were not reported in the provided text.