Glutamine and antioxidant supplementation provide no benefit for critically-ill patients

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1. Glutamine supplementation in intensive care unit (ICU) patients increases mortality while antioxidant supplementation does not provide any additional benefit. 

2. Elevated urea levels were observed more frequently in patients receiving glutamine. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Critically ill patients are a population with known oxidative stress. Previous meta-analyses of smaller randomized control trials (RCT) demonstrated reduced mortality in critically ill patients who received glutamine and antioxidants in the intensive care unit (ICU). This study was the first large-scale international multi-center RCT to demonstrate that glutamine increases mortality and antioxidants provide no significant benefit in ICU patients. The randomized groups in this study were homogenous and the results can be generalized to most patients in ICU with multi-organ failure.

This study was unique from prior studies in that critically ill patients with multiorgan failure were accepted into the study, and were also receiving the highest possible dose of glutamine. These differences may have accounted for the statistical differences observed and might explain the dissonance with prior findings. Future studies might focus on elucidating the mechanism of action of glutamine in critically-ill patients.

Click to read the study, published online today in NEJM

In-Depth [randomized, multicenter, international study]: This study included 1,223 intensive care unit (ICU) patients with multi-organ failure from 40 different ICUs in Canada, the United States and Europe. Patients were randomized into one of four groups – placebo, glutamine, antioxidants, glutamine plus antioxidants. The primary outcome was 28-day mortality, which was 32.6% v. 25.3% in the glutamine-only v. placebo (p=0.05) and 29.0% v. 25.3% in the antioxidant v. placebo (p=0.48). The overall adjusted odds ratio with glutamine was 1.28 (p=0.05) and 1.09 (p=0.48) with antioxidants. Elevated urea levels (>50 mmol/L) were observed in 13.4% and 4.0% in the glutamine v. no glutamine groups (p<0.001).

By Jonathan Liu and Mitalee Patil

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