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Extra glutamine increases mortality in critically ill adults

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2527 (Published 24 April 2013) Cite this as: BMJ 2013;346:f2527

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Early glutamine supplementation looked harmful to critically ill adults in a large trial that tested the supplements in intensive care units in Canada, the US, and Europe. Participants with multiorgan failure treated with glutamine had higher mortality than placebo controls. The difference was on the cusp of statistical significance in the primary analysis (mortality at 28 days 32.4% v 27.2%; adjusted odds ratio, 1.28, 95% CI 1.00 to 1.64) and definitely significant in two secondary analyses (in-hospital mortality 37.2% v 31%; P=0.02; 6 month mortality 43.7% v 37.2%; P=0.02).

The authors expected the opposite. A previous meta-analysis had reported benefits, and glutamine was thought to be a key amino acid during the early days of a critical illness. Using a factorial design, the trial also tested a cocktail of antioxidants, such as selenium. These supplements made no difference to mortality or any other outcome relative to placebo.

The trial was big enough and powerful enough to rule out any benefits from either intervention, says a linked editorial (p 1549). We must readjust our intuitive assumptions about the role of glutamine in critical illness and accept that supplementation is ineffective and may even be toxic. Most of the 1223 participants in this trial were in shock. They were given extra glutamine, extra antioxidants, both, or neither on the day of admission to intensive care, then continuously for up to 28 days.

Notes

Cite this as: BMJ 2013;346:f2527

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