title: A randomized trial of glutamine and antioxidants in critically ill patients.
abstract: 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.).
authors.affiliation: Kingston General Hospital, Kingston, ON, Canada. dkh2@queensu.ca
authors.forename: Daren
authors.initials: D
authors.lastname: Heyland
authors.forename: John
authors.initials: J
authors.lastname: Muscedere
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wischmeyer
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Gwynne
authors.initials: G
authors.lastname: Jones
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.forename: Gunnar
authors.initials: G
authors.lastname: Elke
authors.forename: Mette M
authors.initials: MM
authors.lastname: Berger
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Day
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D016638:Critical Illness; D005260:Female; D005973:Glutamine / Q000009:adverse effects / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012121:Respiration, Artificial; D016037:Single-Blind Method; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000975:Antioxidants; D005973:Glutamine