APPLIED NUTRITIONAL INVESTIGATION Influence of Polymeric Enteral Nutrition Supplemented With Different Doses of Glutamine on Gut Permeability in Critically Ill Patients Nicola ´s Velasco, MD, Glenn Hernandez, MD, Carol Wainstein, MD, Luis Castillo, MD, Alberto Maiz, MD, Francisco Lopez, MD, Sergio Guzman, MD, Guillermo Bugedo, MD, Ana Marı ´a Acosta, BS, and Alejandro Bruhn, MD From the Hospital Clı ´nico, Facultad de Medicina, Pontificia Universidad Cato ´lica de Chile, Santiago, Chile OBJECTIVES: To evaluate the effect of glutamine-supplemented polymeric enteral formulas on the recov- ery of gut-permeability abnormalities in critically ill patients. METHODS: Twenty-three patients were randomized to receive a conventional casein-based enteral formula (ADN), ADN plus glutamine in a dose of 0.15 g  kg -1  d -1 or ADN plus 0.30 g  kg -1  d -1 of glutamine for 8 d. The lactulose mannitol permeability test (L/M) was performed at baseline and at the end of the study. Nineteen healthy volunteers served as controls for the L/M test. RESULTS: An increase in permeability compared with control subjects was observed in patients at baseline (mean  standard error of the mean; L/M ratio: 0.11  0.03 and 0.025  0.004, respectively; P  0.02). The L/M ratio improved after the period of enteral nutrition as a whole (initial L/M: 0.11  0.03, final L/M: 0.061  0.01; P  0.03), but no difference was found between groups. CONCLUSIONS: Even though polymeric enteral nutrition was associated with a significant improvement in the L/M ratio, glutamine supplementation did not show a specific influence in improving recovery of gut permeability in critically ill patients. Nutrition 2001;17:907–911. ©Elsevier Science Inc. 2001 KEY WORDS: gut permeability, glutamine, lactulose mannitol test, enteral nutrition INTRODUCTION A permeable gut after ischemia or severe injury in critically ill patients has been implicated as a potential source of systemic proinflammatory mediators, which might contribute to the patho- genesis of the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome. The systemic absorption of mediators such as bacteria, endotoxins, or cytokines can be pre- vented by the maintenance of an intact gut barrier. 1–2 Several factors such as splanchnic ischemia, enteral fasting, and immuno- logic depression may contribute to the loss of the barrier function after a severe injury. 1–2 Although the intestinal barrier is a complex defense influenced by several factors other than the simple structure of gut epithelium, different functional tests such as the lactulose/mannitol (L/M) ratio in urine have been used to assess permeability. Experimental and clinical studies using the L/M test have shown that total parenteral nutrition without glutamine does not prevent the functional abnor- malities of the gut epithelium that develop after long-term fasting. 3–5 These abnormalities can be avoided by the administra- tion of enteral nutrition when feasible. This has raised interest in the study of enterocyte metabolism to develop an optimal enteral formula that might contribute to the restoration of normal gut- barrier function. The small bowel enterocyte uses glutamine as one of its main nutrients, 6–9 a fact that has generated great interest in evaluating the role of this amino acid on the nutrition of critically ill pa- tients. 10 Glutamine-supplemented elemental diets have been asso- ciated with improved nutrition status, increased epithelial-gut cell proliferation, and decreased mortality in animal models after burns, extensive radiation, or enterocolitis when compared with an elemental formula without glutamine. 11,12 Conventional enteral- nutrition formulas that use intact proteins (e.g., casein or soy) provide a moderate amount of glutamine (3.55 to 5.15 g/1000 kcal). 13 There are no clinical data concerning the use of such enteral formulas supplemented with glutamine and their impact on gut permeability. We hypothesized that the glutamine in casein was enough to promote an appropriate recovery of gut permeability in critically ill patients and that supplemental doses of glutamine did not have an additional effect. MATERIALS AND METHODS All patients or their closest relatives signed informed consent before entering the study. The study protocol was approved by the Institutional Review Board of the Catholic University Medical School. Patients admitted to the Surgical Intensive Care Unit of our hospital between May 1994 and November 1995 were recruited if they were critically ill with at least 4 d of enteral fasting and able to start enteral feeding by a nasoduodenal tube or jejunostomy. Patients were excluded if they presented any of the following conditions: hepatic (bilirubin  3 mg%) or renal (creatinine  2 mg%) failure, disseminated neoplasia, active chemo- or radiother- apy for cancer, active coagulopathy, hemodynamic instability, and contraindications for enteral feeding (high-flux intestinal fistulae, severe diarrhea, or persistent ileus). Therapeutic nutrition goals were to provide 25 to 30 kcal  kg -1  d -1 and 1.5 to 2.0 g  kg -1  d -1 of protein. Supplementary This study was supported by grant 1940597 from FONDECYT/Chile. Correspondence to: Glenn Hernandez, MD, Facultad de Medicina, Pontifi- cia Universidad Cato ´lica de Chile, Casilla 114-D Santiago, Chile. E-mail: glenn@med.puc.cl Nutrition 17:907–911, 2001 0899-9007/01/$20.00 ©Elsevier Science Inc., 2001. Printed in the United States. All rights reserved. PII S0899-9007(01)00613-X