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Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study.

Publication ,  Journal Article
Heyland, DK; Dhaliwalm, R; Day, A; Drover, J; Cote, H; Wischmeyer, P
Published in: JPEN J Parenter Enteral Nutr
2007

BACKGROUND: Supplementation with glutamine and antioxidants may be associated with an improvement in clinical outcomes, but the optimal dose of these substrates is unknown. The purpose of this study was to determine the safety of high doses of glutamine combined with antioxidants in critically ill patients. METHODS: We conducted a single-center, open-label, dose-escalating clinical trial. Mechanically ventilated adult patients with clinical evidence of hypoperfusion were sequentially enrolled to 1 of 5 groups. Group 1 (n = 30): no supplementation; group 2 (n = 7): 0.35 g/kg/d of glutamine IV; group 3 (n = 7): same as group 2 plus 15 g/d of glutamine and 150 microg of selenium enterally; group 4 (n = 7): same as group 2 plus 30 g/d of glutamine and 300 microg of selenium enterally; and group 5 (n = 7): same as group 4 plus an additional 500 microg of selenium IV. After enrollment, nutrients were started as soon as possible. All patients were fed enterally according to clinical practice guidelines. RESULTS: The primary outcomes for this study were change in sequential organ function assessment (SOFA) score and safety parameters. Secondary outcomes included whole blood glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and blood cells' mitochondrial DNA/nuclear DNA ratio (RATIO). There were no adverse events attributable to the study nutrients, and the maximum and Delta SOFA did not differ across groups. In group 2, a significant decrease in GSH levels was observed (p = .03). With subsequent groups, the slopes straighten out and the p values are no longer significant, suggesting a greater preservation of GSH levels with escalating doses. In group 2, the slope of the line representing TBARS was horizontal. With subsequent groups, the slopes decrease, and by group 5, this decrease reaches statistical significance (p = .03), suggesting a greater reduction in oxidative stress with the higher doses in group 5. The difference in slopes across all groups describing the mitochondrial RATIO is statistically significant (p = .001), again suggesting that, with higher doses, there is increased mitochondrial function. CONCLUSIONS: The doses of glutamine and antioxidants tested in this study seem to be safe and may have positive effects on some mechanistic endpoints. A larger trial will be necessary to confirm their therapeutic effects.

Duke Scholars

Published In

JPEN J Parenter Enteral Nutr

DOI

ISSN

0148-6071

Publication Date

2007

Volume

31

Issue

2

Start / End Page

109 / 118

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thiobarbituric Acid Reactive Substances
  • Selenium
  • Oxidative Stress
  • Nutrition & Dietetics
  • Middle Aged
  • Male
  • Humans
  • Glutathione
  • Glutamine
 

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Heyland, D. K., Dhaliwalm, R., Day, A., Drover, J., Cote, H., & Wischmeyer, P. (2007). Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study. JPEN J Parenter Enteral Nutr, 31(2), 109–118. https://doi.org/10.1177/0148607107031002109
Heyland, Daren K., Rupinder Dhaliwalm, Andrew Day, John Drover, Helene Cote, and Paul Wischmeyer. “Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study.JPEN J Parenter Enteral Nutr 31, no. 2 (2007): 109–18. https://doi.org/10.1177/0148607107031002109.
Heyland DK, Dhaliwalm R, Day A, Drover J, Cote H, Wischmeyer P. Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study. JPEN J Parenter Enteral Nutr. 2007;31(2):109–18.
Heyland, Daren K., et al. “Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study.JPEN J Parenter Enteral Nutr, vol. 31, no. 2, 2007, pp. 109–18. Pubmed, doi:10.1177/0148607107031002109.
Heyland DK, Dhaliwalm R, Day A, Drover J, Cote H, Wischmeyer P. Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study. JPEN J Parenter Enteral Nutr. 2007;31(2):109–118.
Journal cover image

Published In

JPEN J Parenter Enteral Nutr

DOI

ISSN

0148-6071

Publication Date

2007

Volume

31

Issue

2

Start / End Page

109 / 118

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thiobarbituric Acid Reactive Substances
  • Selenium
  • Oxidative Stress
  • Nutrition & Dietetics
  • Middle Aged
  • Male
  • Humans
  • Glutathione
  • Glutamine