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REducing Deaths due to OXidative Stress (The REDOXS© Study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients

Published online by Cambridge University Press:  07 March 2007

Daren K. Heyland ,
Rupinder Dhaliwal ,
Andrew G. Day ,
John Muscedere ,
John Drover ,
Ulrich Suchner  and
Deborah Cook
Daren K. Heyland*
Affiliation:
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
Rupinder Dhaliwal
Affiliation:
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
Andrew G. Day
Affiliation:
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
John Muscedere
Affiliation:
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
John Drover
Affiliation:
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
Ulrich Suchner
Affiliation:
Ludwig Maximilians University, Munich, Germany
Deborah Cook
Affiliation:
St Joseph's Healthcare, Hamilton, Ontario L8N 4A6, Canada
*
*Corresponding author: Dr D. K. Heyland, fax +1 613 548 1351, email dkh2@post.queensu.ca
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Abstract

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Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2×2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

Keywords

Enteral nutritionCritical illnessGlutamineAntioxidants
Type
BAPEN Symposium 4 on ‘Glutamine and antioxidants in critical care’
Information
Proceedings of the Nutrition Society , Volume 65 , Issue 3 , August 2006 , pp. 250 - 263
Copyright
Copyright © The Nutrition Society 2006

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