Zhu-Ming Jiang

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial

BACKGROUND This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. METHODS Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. RESULTS The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay was significantly shorter in the gln group than controls (67 +/- 4 days versus 73 +/- 6; p = .026). On day 30, wound healing was 86% +/- 2% complete in the gln group compared with 72% +/- 3% in controls (p = .041). Total cost of hospitalization was 62794 +/- 6178 RMB (dollar 7593 +/- 747 US dollars) in the gln group and 68996 +/- 8620RMB (dollar 8343 +/- 1042, p = .031) in controls, although the cost of the enteral nutrition was higher in the gln-supplemented patients. CONCLUSION Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels, improved gut permeability, and initially decreased plasma endotoxin levels in severely thermally injured patients. These alterations were associated with a reduction in the length of hospitalization and lower costs.

Effects of Alanyl-Glutamine on Gut Barrier Function

Traditional parenteral nutrition (PN) and chemotherapy may lead to changes of mucosal morphology and gut barrier function. This study investigated the effect of alanyl-glutamine (Ala-Gln) on intestinal morphology and gut barrier function in PN-fed rats challenged with 5-fluorouracil (5-FU). Male Wistar rats were centrally catheterized and then randomized to receive PN devoid of glutamine (control group; n = 10) or 3% Ala-Gln-supplemented PN (study group; n = 10) for 7 d. Intestinal permeability to lactulose and mannitol was measured before and 72 h post 5-FU administration on day 4. Serum glutamine concentration and jejunal mucosal structure were maintained in the study group compared with the control group (P 0.05) on day 3. On day 7, L/M was unaltered in the study group, whereas it increased in the control (0.042 +/- 0.004634 versus 0.029 +/- 0.002020; P < 0.05). We concluded that glutamine dipeptide maintained intestinal mucosal morphology and barrier function in PN-fed rats challenged with 5-FU.

Impact of perioperative treatment of recombinant human growth hormone on cell immune function and intestinal barrier function: Randomized, double-blind, controlled trial

The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation (p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values (p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.

Postoperative Fall in Serum Zinc Concentrations Unaffected by Intravenous Zinc Therapy

The serum zinc levels and urinary zinc outputs before and after a middle severity operative trauma were investigated. The serum zinc concentration dropped markedly 6 hr after operation in both supplemented and nonsupplemented groups. It gradually returned to near normal without exogenous supplies of zinc. Provision of therapeutic doses of zinc could not prevent the abrupt dip of the serum zinc level. The possible mechanism of such changes are discussed briefly.