A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.
What this study found
Glutamine did not shorten time to discharge alive from the hospital. Median time to discharge was 40 days vs 38 days (subdistribution hazard ratio 0.91; 95% CI 0.80–1.04; P = 0.17). Six-month mortality was 17.2% vs 16.2% (hazard ratio 1.06; 95% CI 0.80–1.41). No substantial differences in serious adverse events. Conclusion: Enteral glutamine at 0.5 g/kg/day does not improve discharge timing, mortality, or major outcomes in adults with severe burns; routine use is not supported.
- Study & population
- International multicenter, double-blind, parallel-group randomized, placebo-controlled trial in adults with deep second- or third-degree burns requiring skin grafting; enrolled within 72 hours of hospital admission; 1209 randomized at 54 burn units in 14 countries (596 to glutamine, 604 to placebo); mean age around 49 years; majority male.
- Intervention
- 0.5 g/kg/day enteral glutamine (based on pre-burn body weight; obesity-adjusted weight used if BMI ≥35), delivered every 4 hours via a feeding tube or 3–4 times daily by mouth, for 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever comes first.
- Key limitation
- - Low accrual leading to midtrial changes to sample size and primary outcome; - Low completion rate of 6-month survivor questionnaires; - Midtrial sample size re-estimation and changes may have slightly distorted type I/II error rates.
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Open PDFOriginal abstract
BACKGROUND Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth 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, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).