SAFETY AND EFFICACY OF INCREASING DOSAGES OF GLYCYL-GLUTAMINE FOR TOTAL PARENTERAL-NUTRITION IN POLYTRAUMA PATIENTS

Supplementation of parenteral nutrition with glutamine (GLN) has been suggested to improve the efficacy of nutritional support by stimulatin g protein synthesis and improving immunocompetence. In the present stu dy we investigated the impact of infusing the dipeptide glycyl-glutami ne (GLY-GLN) at increasing dosages on plasma amino acid concentrations in patients with polytrauma. Nine polytraumatized patients were rando mly assigned according their age and their trauma score to three exper imental groups. Group I received 280, group II 450, and group III 570 mg GLY-GLN per kg body weight/day for a period of four days (3rd to 7t h posttraumatic day), resulting in a maximum daily GLN administration (calculated for a 70 kg patient) of 14 g, 21 g and 28 g, respectively. Seven polytraumatized patients receiving the nutrition solution witho ut GLY-GLN supplementation served as controls. Ali patients received t otal parenteral nutrition with an average amino acid administration of 1.1 g/kg/day and a total energy intake of 30 kcal/kg/day. GLY-GLN inf usion did not evoke any side effects. In comparison with the control g roup, arterial plasma GLN concentrations increased significantly on da y I after start of infusion in groups II and III, but remained raised throughout the study period only in group III (p < 0.003). Similarly, plasma GLY concentrations were also significantly raised in group III (p < 0.04). The maximum increase of plasma GLY was found on the second infusion day, after which plasma concentrations of GLY fell to concen trations even below those observed in the control group at the end of the study period. Excretion of GLY GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible. We conclude from this first ava ilable dose finding study on glutamine-containing dipeptides that in p olytraumatized patients infusion of 570 mg/kg/day of GLY-GLN (correspo nding to 28 g glutamine or 40 g dipeptide/70 kg, respectively) is nece ssary to induce a sustained effect on plasma glutamine concentrations. No pathological accumulation of free glycine or of the dipeptide was seen with any of the three dosage steps of GLY-GLN. Thus, the administ ration of even high doses of GLY-GLN is feasible and safe in patients with polytrauma and is not associated with any relevant renal substrat e loss.