Glutamine, thought to have beneficial effects for severe injury recovery, did not reduce the time-to-discharge when given supplementally to patients with severe burns, according to data from a double-blind, randomized, placebo-controlled trial published in The New England Journal of Medicine.
Investigators randomly assigned adult patients with deep second- or third-degree burns 1:1 to receive either 0.5 g/kg per day of enteral glutamine or placebo within 72 hours of hospital admission. Treatment lasted until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission — whichever came first. The primary outcome was the time to discharge alive from the hospital, and investigators calculated subdistribution hazard ratios (HRs) for discharge alive. The secondary outcome was 6-month mortality, which was estimated using the Kaplan-Meier method and compared between trial groups using a Cox proportional-hazards model.
There were 1200 patients with severe burns included in the analysis, 596 in the glutamine group and 604 in the placebo group. In both groups, the mean age was approximately 49 years, almost 73% were men, and about 75% were White. The median time to discharge alive from the hospital was 40 days (IQR, 24-87) in the glutamine group and 38 days (IQR, 22-75) in the placebo group (subdistribution HR, 0.91; 95% CI, 0.80-1.04; P =.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (HR, 1.06; 95% CI, 0.80-1.41). There were no significant differences between groups for serious adverse events.
The study was limited by low rates of 6-month survivor questionnaires.
Study authors found the results to be surprising given glutamine’s reportedly positive effect on severe burns in previous research, albeit most of them small single-center trials. “Our results were unexpected given the magnitude of the signal from previous trials of supplemental glutamine in burn-injured patients,” they acknowledged. They therefore cautioned against “the practice of translating the results of single-center trials into clinical-practice recommendations, as occurred with enteral glutamin supplementation.”
Heyland DK, Wibbenmeyer L, Pollack JA, et al, with the RE-ENERGIZE Trial Team. A randomized trial of enteral glutamine for treatment of burn injuries. N Engl J Med. 2022;387(11):1001-1010. doi:10.1056/NEJMoa2203364