Glutamine to ICU patients

Abstract: Intravenous glutamine supplementation to intensive care patients using a glutamine containing dipeptide is now widely accepted in clinical practice. There are evidences that glutamine supplementation of ICU patients in need of parenteral nutrition improves mortality and morbidity. The beneficial effects may be extended also to ICU patients on combined enteral and parenteral nutrition and perhaps also to ICU patients on enteral nutrition only. The effect of intravenous and/or enteral glutamine supplementation to these patient groups is presently not conclusive. To facilitate clinical use of glutamine supplementation a number of safety aspects are considered in this thesis work. The possibility to administer the concentrated glutamine containing dipeptide solution in peripheral vessels, and the metabolic tolerance of the dipeptide formulation in ICU patients. Metabolic tolerance was assessed as the absence of accumulation of the dipeptide, the absence of urinary losses of the dipeptide, and the clearance of dipeptide and constituent amino acids over time. Furthermore, the possible losses of the dipeptide and the constituent amino acids during continuous renal replacement therapies in ICU patients with kidney failure have not been clarified. The extent of glutamine losses into the ultrafiltrate and the possibility that exogenous supplemented glutamine will be lost into the ultrafiltrate to a high degree have been addressed. Finally the concern that exogenous provided glutamine may be converted into glutamate in the brain of head trauma patients has been a concern. Head trauma patients some times suffer from multiple organ failure and hence maybe treated with exogenous glutamine. The suggestion of a connection between elevated intracerebral glutamate levels and an unfavourable outcome in the head trauma patients has been suggested. Therefore the possible connection between exogenous glutamine supplementations and the level of free glutamate interstitially in the brain and the balance of free glutamate and glutamine across the brain was investigated. The results show that a glutamine containing dipeptide in a concentrated solution may be administered in the peripheral vein without any signs of inflammatory reaction. In addition, the glutamine containing dipeptide is metabolically well tolerated in ICU patients. The losses of exogenously provided glutamine into the ultrafiltrate during continuous renal replacement therapy are not different from a situation where no exogenous supply is given. The increased loss into the ultrafiltrate is on the contrary an argument to increase the exogenous supplementation of glutamine. Finally, there was no connection between glutamine supplementation and the level of free glutamate interstitially in the brain and the balance of glutamate across the brain in head trauma patients. In addition, posthoc analyses were performed demonstrating that the endogenous rate of appearance of glutamine (estimate of glutamine production) in ICU patients is of the same magnitude as in healthy individuals. And it is suggested that this endogenous production is not inhibited by exogenous glutamine supplementation. The results presented in this thesis work provide evidence that studies to elucidate outcome advantages for ICU patients in relation to intravenous glutamine supplementation are safe and can be encouraged. Furthermore new insights in glutamine production and handling of exogenous glutamine supplementation were gained.