WHAT THIS STUDY ADDS:

• Glutamine, delivered in water via a nasoenteral feeding tube, decreases bacteremia and may increase survival in critically ill burn patients.

MONTREAL—A well-designed clinical trial has shown that glutamine may be lifesaving for at least some critically ill patients.[1] Adult burn victims who received enteral glutamine supplementation experienced significant reductions in the risk of blood infection and death.

Glutamine, an essential amino acid, is an important energy substrate for immune cells and the intestinal epithelium, and also serves as a nucleotide precursor. These biologic properties have made glutamine a good candidate for nutritional intervention in critical illness, and its ability to reduce infectious morbidity in trauma patients is recognized. However, glutamine is seldom (if ever) included in standard nutritional support solutions.

The results of the new study present a strong argument for using glutamine routinely in critically ill burn victims. “Given the fact that glutamine is safe, relatively inexpensive, and easy to administer, I would recommend its administration to severely burned patients,” said Dominique Garrel, MD, the study’s principal investigator and a Professor of Medicine at the University of Montreal. “Glutamine’s cost is about US $40 per 300 grams, which makes the cost of this treatment $4 a day. The claim for glutamine benefits, however, should be limited to the prevention of septicemia and should not include a reduction in mortality, because mortality was not a [primary] end point in our study. Also, the number of patients was small.”

DELIVERING GLUTAMINE EFFECTIVELY

Dr. Garrel and his colleagues were the first to measure the impact of glutamine in burn patients. They had hypothesized a role for glutamine in the treatment of these patients given the pronounced muscle and plasma glutamine depletion in severe burn injury.

To investigate this, the researchers randomly assigned 45 patients with severe burns to receive either 4.3 g of glutamine (every four hours for a total of 26 g/d) or an isonitrogenous control mixture of aspartic acid, asparagine, and glycine. The interventions were delivered to the patients in 50 mL of water via a nasoenteral feeding tube (started within 24 hours of hospital admission) and were continued until complete healing occurred. Both patients and practitioners were blind to the type of treatment given.

“Separate administration of glutamine as boluses is preferred,” Dr. Garrel said, “because the amount given does not depend on the volume of enteral solution received by the patient,” which varies with clinical status. He explained that the glutamine regimen his team used was chosen in part to address the fact that some previous trials had failed to detect a benefit of glutamine administration in critically ill patents. These trials, he said, provided glutamine at a dosage of less than 20 g/d and mixed the glutamine with the enteral solution. “Glutamine is not stable in solution, and the addition of the amino acid to a feeding formula is difficult. A dipeptide, glycyl-glutamine could be used, but it is much more expensive,” he added.

IMPORTANT BENEFITS

Included in the final analysis were 41 patients, 19 in the glutamine group and 22 in the control group. The clinical and nutritional characteristics of the patients were similar. Of the four who were excluded, three had died within 72 hours and one was unable to receive enteral nutrition.

Mortality was significantly lower in the patients given glutamine than in those receiving placebo. In the intention-to-treat analysis (which included all 45 subjects), 12 patients from the control group died, compared with two patients from the glutamine group. In the per-protocol analysis (which excluded the four subjects described above), the respective numbers of deaths were eight and zero.

Among the control subjects, mortality was largely the result of infection. The frequency of positive blood cultures was about three times higher in the control patients than in the glutamine patients (the number of positive cultures, in days per patient, was 4.3 vs 1.2, with the difference reaching statistical significance).

Pseudomonas aeruginosa was the infecting organism in six of the 10 control patients who had a positive blood culture but in none of the seven glutamine patients with documented infection. Moreover, of the eight control patients who died, four had positive blood cultures for P aeruginosa. No dominant bacterium was found in the blood of the glutamine-supplemented patients.

Dr. Garrel said, “There is a fascinating hypothesis about the effect of glutamine on P aeruginosa,” based on work by researchers from Chicago. “Glutamine appears to be an essential nutrient for the microbe. When glutamine is insufficient in the culture milieu, the bacteria proliferate and damage the epithelial barriers,” he explained. “It could then be that enteral glutamine administration stabilizes P aeruginosa in the gut and prevents its pathogenic action on the host.”

OTHER FINDINGS

Between-group differences were not observed in the length of care (0.90 vs 0.98 days per total burn surface area, for glutamine vs controls); in the rate of wound infection; or in the level of phagocytic activity of circulating polymorphonuclear cells (glutamine has been shown to effect this change in children with burn injuries). In addition, no differences were seen in plasma concentrations of interleukin 6 and interleukin 2 receptor alpha or in serum glutamine levels.

—Verna L. Schwartz, MS

Reference
1. Garrel D, Patenaude J, Nedelec B, et al. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003;31:2444-2449.

Return to table of contents