Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine. Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure.

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