Glutamine Reduces Infection in Trauma Patients
Abstract & Commentary
Synopsis: In patients with multiple trauma, glutamine-enriched total enteral feeding was associated with lower incidences of pneumonia, sepsis, and bacteremia than a balanced, isonitrogenous, and isocaloric enteral feeding regimen.
Source: Houdijk AP, et al. Lancet 1998;352:772-776.
A total of 80 patients with multiple trauma were randomly allocated to either glutamine-supplemented enteral feeding (52 g protein [30.5 g glutamine/100g protein], 165 g carbohydrate, 15 g fat, and 1000 kcal/L) or an isocaloric, isonitrogenous control feeding (3.5 g glutamine/100 g protein). Both feedings contained the same amount of arginine and other essential amino acids. Eligible patients had an Injury Severity Score (ISS) of more than 20, were between 16 and 65 years of age, and had an expected survival rate of more than 48 hours as estimated by both the Glasgow Coma Scale Score and ISS. The patients were assigned to feeding by the pharmacist using computer-generated randomization, and all participants were unaware of treatment allocation. Feeding was started within 48 hours of admission and was continuously given, aimed to reach 75% of the basal energy expenditure within 72 hours. The caloric requirement was estimated and adjusted by indirect calorimetry. No other form of nutrition was given. The enteral feeding lasted at least five days. The end points of the study were infectious morbidity during the first 15 days. The concentrations of glutamine, arginine, and soluble tumor necrosis factor (TNF) receptors p55 and p75 in the blood were determined on the appropriate days.
The incidences of pneumonia, bacteremia, and sepsis were significantly lower in the glutamine-supplemented group in comparison with the control group (17% vs 45%, 7% vs 42%, and 3% vs 26%, respectively). In the treated patients, plasma concentrations of arginine and glutamine became significantly higher on days 3-5, and serum concentrations of soluble TNF-receptor p55 and p75 became lower on days 4-7.
Comment by Jun Takezawa, MD
Glutamine, structurally different from glutamic acid, has been called a "conditionally essential" amino acid, which cannot be sufficiently synthesized to meet the necessary requirements under a stressed state such as infection, trauma, or surgery. Under stress, skeletal muscles are catabolyzed, releasing amino acids, one-third of which consist of glutamine. When glutamine is given intravenously, this muscle catabolism is suppressed. In patients with multiple trauma, burns, and sepsis, the amount of glutamine in the skeletal muscle is decreased. Glutamine is also known as a respiratory fuel for mucosal cells in the intestine and colon. However, the most important roles are to multiplicate neutrophiles and to facilitate and assist in the killing of bacteria. These points comprise the background and rationale that glutamine may improve infectious mortality and morbidity in patients in a catabolic condition such as trauma.
Houdijk and colleagues conducted a well-designed randomized controlled trial (RCT) in the double-blinded fashion. The first RCT on glutamine-supplemented enteral feeding demonstrated improved six-month mortality in ICU patients (Nutrition 1997;13:295-302). This is the second RCT that has described the possible benefit of glutamine-supplemented enteral feeding in reducing infectious morbidity, which hopefully will also be associated with improved final outcomes such as mortality and medical costs.
Houdijk et al were interested in intermediate outcomes such as infectious morbidity and biochemical parameters such as soluble TNF receptors, and did not describe final outcomes in the patients studied. The only information related to patient outcome presented in this paper was the median stay of the patients in both groups, which was found not to be significantly different. It is surprising that the significantly higher incidence of infectious episodes in the control group did not result in the longer hospital stay. Future investigators are encouraged to conduct another RCT focusing on the final outcomes such as mortality and medical cost, as well as length of ICU and hospital stays and infectious morbidity. Until the final conclusion is made, glutamine-enriched enteral feeding for posttraumatic patients cannot be recommended.