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Supplementing the diet with glutamine didn't improve outcomes for second- and third-degree burn patients, the randomized trial showed.

Multiple daily doses of enteral glutamine didn't reduce median time to discharge alive from the hospital compared with placebo (40 vs 38 days, HR 0.91, 95% CI 0.80-1.04), reported Daren K. Heyland, MD, of Queen's University in Kingston, Ontario, Canada, and colleagues.

Furthermore, there were no benefits in 6-month mortality (17.2% vs 16.2%, respectively, HR 1.06, 95% CI 0.80-1.41), nor for length of stay measures or bacteremia.

The study was published in the in conjunction with a presentation at the European Burns Association Congress in Turin, Italy.

"Our results were unexpected given the magnitude of the signal from previous trials of supplemental glutamine in burn-injured patients," the researchers wrote.

International nutrition guidelines have recommended enteral glutamine for major burn patients on the basis of dramatic benefits suggested by aggregated data from small, single-center trials.

However, more recent findings in critical illness showing or even from glutamine supplementation warranted better data in the burn setting, Heyland's group noted.

"Glutamine was of particular interest because it is vital for a number of key stress-response pathways in serious illness," they wrote.

But in the face of substantially improved mortality and morbidity "with greater attention to initial resuscitation, wound management, and early surgical intervention, it may be unlikely that a single-nutrient replacement strategy will affect the underlying pathophysiological processes," they suggested.

The concept made sense, agreed Taryn E. Travis, MD, of the Burn Center at MedStar Washington Hospital Center in Washington, D.C. "It's part of these pathways where, looking at it logically, you would think, 'Well, of course, it should make a difference,'" she said.

"We've sort of hit this point now where people are looking at other things that we may be able to do outside of giving them good surgeries that could potentially help people survive their injuries," Travis commented in an interview with 乌鸦传媒. "At the end of the day, the thing that allows a burn patient to survive and make it out of the hospital is getting their skin healed. By proxy, anything that helps that happen faster is life- and lifestyle-impactful to burn patients."

Being nutritionally deficient slows down that process, she noted. Whether glutamine speeds it up in some way that impacts quality of life or other endpoints not looked at in the trial could still be possible, she added.

The RE-ENERGIZE trial included 1,209 patients with deep second- or third-degree burns (≥10% to ≥20% of total body-surface area, depending on age; average 33%).

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.

However, Heyland and colleagues noted that "the large number of diverse patients recruited across a large global network of burn units supports broad generalizability of the findings."

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