Glutamine in critically ill patients: is it a fundamental nutritional supplement?

Abstract

Glutamine is the most abundant free amino acid in the human body and is necessary to modulate the inflammatory and oxidative stress responses in patients.(1,2) Systemic glutamine availability is determined by the balance of endogenous glutamine production (mainly in muscular tissue) and its use by glutamine consuming organs (gut, kidney, liver and the immune system). Several studies show that in catabolic intensive care unit (ICU) patients, the endogenous production of muscular glutamine is increased while the plasma levels of glutamine are decreased, indicating elevated glutamine needs.(3,4) We know also that low plasma glutamine values (< 420μmol/L) upon admission are related to increased mortality.(5) These findings are the rationale for the use of glutamine supplementation in the ICU population in order to replenish the muscle pool of glutamine, attenuate the efflux of this amino acid, and provide exogenous glutamine required to meet the elevated organ needs for improvement in protein synthesis, modulation of the immune system, reduction of oxidative stress, and preservation of the gut barrier. However, recent observations challenge this hypothesis. The plasma levels of glutamine are extremely variable in the ICU population(6) and are not always associated with increased mortality.(7) The glutamine supplementation does not stop the glutamine efflux from muscle because the endogenous muscular production and plasma levels of glutamine are related to the severity of the illness.(8) Intensive care unit patients are considered to be immunosuppressed as evidenced by reduced levels of and the presence of dysfunctional T lymphocytes, altered neutrophil activity and an imbalance in the production of cytokines.(9-13) The demonstration of the benefit of glutamine in increasing the number and functionality of effector cells of the immune response is evident in some studies,(14-19) while in others that answer is not so obvious.(20,21) We found (personal communication)(22) that in the ICU population, glutamine supplementation (0.40g/Kg/day) via parenteral nutrition improved cellular immune function with significant increases in CD14 and CD14 HLA-DR monocytes and significant decreases in T regulatory cells with a significant reduction in the appearance of nosocomial infection. Over the years, many studies examining glutamine in ICU populations have presented controversial results. We can differentiate between the small monocentric studies of the early years showing a significant reduction in Paulo Martins1