The effects of supplemental glutamine dipeptide on gut integrity and clinical outcome after major escharectomy in severe burns: a randomized, double-blind, controlled clinical trial

Objective: To evaluate the effects of glutamine dipeptides on gut permeability, plasma endotoxin and outcome variables following extensive eschar excision on severe burns. Methods: Thirty patients with severe burns (total body surface burns, 30-50% and third degree burns, 15-25%) were investigated in a prospective, randomized, double-blind clinical trial, to receive parenteral nutrition with (test group) or without (control group) glutamine dipeptide supplementation. Protocol was approved by the local ethical committee and the informed consents were obtained. Parenteral isoenergetic and iso-nitrogenous nutrition was initiated on postoperative day 1 (POD+1) and was administered to both groups until postoperative day 12 (POD+12). Glutamine dipeptide supplement (Dipeptiven (R), Fresenius Kabi, Bad Homburg, Germany) corresponded to 0.5g/kg bw/d (equal to 0.35g glutamine kg bw/d). Plasma glutamine (gln-p), serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (L/M, which reflects gut permeability) were measured throughout the clinical course. Survival rate of skin graft, wound heating time and infection rate were assessed and length of hospital stay and total costs were determined at discharge. Results: The concentrations of gln-p remained low in the control group, but increased in the supplemented group (POD+1: control, 321 +/- 40 mu mol/l, vs. test 431 +/- 52 mu mol/l, P < 0.001; POD+12: control, 397 +/- 38 mu mol/l, vs. test 532.1 +/- 48.9 mu mol/l, P < 0.001). L/M ratio was initially increased in both groups, reflecting enhanced intestinal permeability; the levels being normalized at POD+12. Endotoxin levels were equally elevated in both groups at commencement (POD+1), but decreased significantly in patients receiving gin (POD+12: control, 0.141 +/- 0.045 vs. test 0.112 +/- 0.026, P < 0.043). Wound heating time was significantly shorter in the gin group compared to controls (32 +/- 3 days vs. 37 +/- 6, P < 0.012). Infection rate revealed an obviously lower tendency (control: 26% vs. test 13% NS), yet without approaching a significant difference. Total cost of hospitalization was 45.300 +/- 5.500 RMB (about 5500 US$) in controls vs. 41.400 +/- 3.400 RMB (about 5000 US$) in the gin group, P < 0.029; although it should be emphasized that the cost of glutamine supplementation was accounted for in the calculation. The skin graft survival rate and length of hospital stay were not significantly different between the groups. Conclusion: Supplementation with glutamine dipeptide was associated with enhanced gin plasma concentrations, decreased gut permeability and endotoxin levels as welt as wound heating time and lower cost of hospitalization. (c) 2004 Elsevier Ltd. All rights reserved.