The RE-ENERGIZE trial challenges the thinking around glutamine in Burns care
A worldwide randomised trial, RE-ENERGIZE, of 1,209 patients with severe burns has demonstrated that supplemental glutamine did not reduce the time to discharge alive from the hospital. Furthermore, there were no benefits in 6-month mortality nor for length of stay measures or bacteremia. The study was published in September 2022 in the New England Journal of Medicine in conjunction with a presentation at the European Burns Association Congress in Turin, Italy. Funding was received from the U.S. Department of Defense and the Canadian Institutes of Health Research.
This result was unexpected as glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. However, previous clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of supplementation with glutamine.
International nutrition guidelines have recommended enteral glutamine for major burn patients but more recent findings in critical illness showing no benefit or even harm from glutamine supplementation warranted better data in the burn setting.
Participants were randomized to double-blind treatment within 72 hours after admission to an ICU or burn unit with glutamine (0.5 g/kg body weight per day) or placebo every 4 hours through a feeding tube or three or four times a day by mouth. Treatment continued until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission.
A key limitation was that the trial was stopped before the planned 2,700-patient accrual because of slow enrollment. Once it became clear the original sample size wasn’t feasible, the protocol was amended to switch the primary and secondary outcomes. Another limitation was attrition of participants to the 6-month survivor questionnaires.
The study’s lead, Dr Daren Heyland (Professor of Medicine at Queen’s University and the Director or the Clinical Evaluation Research Unit, Kingston General Hospital, Canada) noted that “the large number of diverse patients recruited across a large global network of burn units supports broad generalizability of the findings.”
At the University Hospitals Birmingham Foundation Trust the study was led by the Director of the Centre for Conflict Wound Research, Professor Naiem Moiemen. RE-ENERGIZE was supported locally by the Delivery Team under the Trauma, Burns and Critical Care umbrella and recruited 29 patients.
Professor Moiemen added ‘this is the first large scale multi-national randomised clinical trial in Burns. This great work has settled a clinical question that was debated within the burn community for decades. The successful conducting of this trial has established a strong research network, essential for further trials that can provide quality evidence in future.’
New England Journal of Medicine
Source Reference: Heyland DK, et al “A randomized trial of enteral glutamine for treatment of burn injuries” N Engl J Med 2022; DOI: 10.1056/NEJMoa2203364.
Glutamine for Burn Patients: Time for a Rethink by Crystal Phend, Contributing Editor, MedPage Today September 9, 2022