Enteral Glutamine in Critical Illness

Randomized Clinical Trial Comparing Enteral Glutamine Supplementation to Standard of Care Enteral Feeding in Critical Illness

Glutamine is an amino acid which is rapidly depleted in critical illness. It is used as energy by cells that line the gut, vital for immune system function, and works as an anti-oxidant. Glutamine supplementation has been shown to improve outcomes in ICU patients. We hypothesize that critically ill patients given extra glutamine will have less of an inflammatory response and therefore better outcomes than patients not given extra glutamine. Our study randomizes patients to tube feeding with OR without extra glutamine to see if it affects patient outcomes as well as markers of inflammation.

Glutamine, a nonessential amino acid, is preferred fuel for rapidly proliferating cells in human body. Those cells include the enterocytes in small intestine, lymphocytes, macrophages, and fibroblasts. Glutamine also transports nitrogen between tissues and serves as a precursor to glutathione which is a potent antioxidant. A healthy human body contains abundant glutamine, either from diet or from skeletal muscle tissue that synthesizes it. During critical illness the demand for glutamine is increased. Rapid depletion of glutamine stores in critically ill patients has been described and correlated to increased mortality. Glutamine depletion may be deleterious in critical illness because of adverse effects on the essential functions mentioned above. For example glutamine depletion may cause gut mucosal barrier function to deteriorate, leading to bacterial translocation and enhanced systemic inflammatory response with increased risk for multisystem organ failure. Clinical trials performed in a wide range of patients with serious illness, including cancer, trauma, burn, major surgery and critical illness, have demonstrated possible benefits of glutamine supplementation. Interpretation of the results of multiple studies is made difficult based on differences in glutamine dosing, route of administration, population studied, and endpoints used. Blood volume analysis has been shown to be a good measure of capillary leak. The DAXOR blood volume analyzer kit was recently approved by the FDA for blood volume analyses and also has the capacity of measuring capillary permeability by looking at the slope of albumin transudation. It is a simpler way to measure capillary permeability than other methods described. Reviewing the previous study results, glutamine supplementation in parental form and with higher dose in various patient populations has shown evidence of being beneficial. Studies of enteral glutamine therapy have also showed benefits, but results are less consistent possibly because of the heterogeneous study methodology described above. Moreover, most of the studies are carried out in burn patients and surgical patients; there were few studies in critical ill medical patients. Finally no study has specifically looked at the mechanism via which glutamine has conferred protection. Comparison: Critically ill patients given enteral tube feeds compared to critically ill patients given enteral tube feeds with supplemental glutamine.

Group A patients will receive 0.5g/kg/day of enteral glutamine daily while they are receiving tube feeds or at the end of 28 days (whichever comes first)

Inclusion Criteria: Admission to MICU/ CICU Age greater than or equal to 18 years old Requirement for enteral nutrition Presence or planned insertion of central venous catheter as part of routine medical care Requirement for mechanical ventilation APACHE II Score >/= 15 Exclusion Criteria: Female of child-bearing age (i.e. less than 45 years old) Enteral nutrition begun prior to randomization Receiving Total Parenteral Nutrition Requirement for protein restriction Creatinine >4 mg/dl History of cirrhosis and/or clinical signs of heptic encephalopathy

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