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Cited by 904Clinical Nutrition and GastroenterologySepsis Diagnosis and TreatmentHyperglycemia and glycemic control in critically ill and hospitalized patients

A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients

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Heyland, Daren, Muscedere, John, Wischmeyer, Paul E., Cook, Deborah, Jones, Gwynne, Albert, Martin, Elke, Gunnar, Berger, Mette M. +1 more·2013·New England Journal of Medicine
DOI 10.1056/nejmoa1212722
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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.).

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Crossref · 10.1056/nejmoa1212722

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  • In REDOXS, glutamine had no effect on infectious complications or organ failure rate.

    “Glutamine had no effect on infectious complications or organ failure rate.”

    From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [48]

  • In REDOXS, 6-month and in-hospital mortality were significantly higher in glutamine-treated subjects.

    “On the contrary, 6-month and in-hospital mortality were significantly higher in glutamine-treated subjects [48].”

    From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [48]

  • In the REDOXS trial, some patients exhibited high levels of plasma GLN.

    “In the REDOXS trial (209), some patients exhibited high levels of plasmaGLN (210, 211).”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [209]

  • The REDOXS study generated concerns because randomization resulted in higher severity with more organ failures in the GLN groups, largely explaining the higher mortality.

    “The REDOXS study (209), designed as a 2 x 2 factorial trial, generated concerns for a number of reasons, including the fact that the randomization resulted in higher severity with more organ failures in the GLN groups, largely explaining the higher mortality (234).”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [209]

  • The absence of an effect of selenium supplementation in the REDOXS trial might have been due to the adequacy of selenium status in the North American population compared with the European population who are selenium borderline deficient.

    “The absence of an effect of Se supplementation in the REDOXS trial (209) might have been due to the adequacy of the Se status in the North American population compared to the European population who are Se borderline deficient (292).”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [209]

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Authors
Heyland, D., Muscedere, J., Wischmeyer, P. E., Cook, D., Jones, G., Albert, M., Elke, G., Berger, M. M., & Day, A. G.
Affiliations
  • Kingston General Hospital (CA)
  • University of Colorado Anschutz (US)
  • St. Joseph’s Healthcare Hamilton (CA)
  • Ottawa Hospital (CA)
  • Hôpital du Sacré-Cœur de Montréal (CA)
  • University Hospital Schleswig-Holstein (DE)
  • Centre Hospitalier Universitaire Vaudois (CH)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2013-04-18
Volume
368
Issue
16
Pages
1489-1497
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1212722
OpenAlex
W2149714337
Cited by
904
References
3
Citations by year
2026: 29 · 2025: 37 · 2024: 43 · 2023: 53 · 2022: 34 · 2021: 56 · 2020: 72 · 2019: 64 · 2018: 62 · 2017: 94 · 2016: 83 · 2015: 116 · 2014: 119 · 2013: 39 · 2012: 1
FWCI
110.42
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
glutamine supplementation, antioxidant supplementation, critically ill patients, multiple organ failure, mechanical ventilation, oxidative stress, 28-day mortality, in-hospital mortality, organ failure, infectious complications, intensive care
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Antioxidants, Female, Glutamine, Humans, Male, Middle Aged, Multiple Organ Failure, Respiration, Artificial, Survival Rate, Logistic Models, Single-Blind Method, Critical Illness, Hospital Mortality, Kaplan-Meier Estimate, Young Adult, Intention to Treat Analysis

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