A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients

Study Questions:

What is the effect of early glutamine and antioxidant supplementation in critically ill patients?


In this blinded 2-by-2 factorial trial, the investigators randomly assigned 1,223 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. Supplements were started within 24 hours after admission to the ICU, and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a p value of <0.044 at the final analysis was considered to indicate statistical significance.


There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00-1.64; p = 0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86-1.40; p = 0.48) or any other secondary endpoint. There were no differences among the groups with respect to serious adverse events (p = 0.83).


The authors concluded that 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.


This international, randomized, blinded trial involving critically ill patients with multiorgan failure reported a nonsignificant increase in 28-day mortality, and significant increases in in-hospital and 6-month mortality were observed with the use of glutamine. No effect of glutamine was observed on any other outcome. Furthermore, antioxidant supplementation was not associated with any effect on study outcomes and conferred no therapeutic benefit. At the current time, there appears to be no role for glutamine and antioxidant supplementation in critically ill patients.

Clinical Topics: Prevention, Nonstatins, Diet

Keywords: Intensive Care Units, Glutamine, Hospital Mortality, Dietary Supplements, Respiration, Artificial, Canada, Multiple Organ Failure, Critical Illness, Europe, United States

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