• DOI:10.1056/NEJMoa1212722
• Corpus ID: 21401818

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

@article{Heyland2013ART,
  title={A randomized trial of glutamine and antioxidants in critically ill patients.},
  author={Daren Keith Heyland and John Muscedere and P. Wischmeyer and Deborah J. Cook and Gwynne Jones and Martin Albert and Gunnar Elke and Mette M. Berger and Andrew G. Day},
  journal={The New England journal of medicine},
  year={2013},
  volume={368 16},
  pages={
          1489-97
        }
}

• D. Heyland, J. Muscedere, +6 authors A. Day
• Published 17 April 2013
• Medicine
• The New England journal of medicine

BACKGROUND
Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.

METHODS
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. 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 less than 0.044 at the final analysis was considered to indicate statistical significance.

RESULTS
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 to 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 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).

CONCLUSIONS
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. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).