Shiva Sharma SHO Breast/Endocrine Surgery Introduction Roles of Glutamine in the body Tissue Protection Anti-inflammatory regulation Preservation of metabolic function Glutamine as therapy Leading cause of death in critically ill patients is sepsis 230,000 deaths in the USA each year secondary to sepsis Mortality rate from sepsis risen by 90% in last 20years Development of multi-organ failure Organ dysfunction secondary to shock, inflammation, metabolic disturbances Non-essential amino acid Most abundant AA in the body 50% free AA in plasma Energy source Precursor to glutathione For nucleic acid synthesis Anti-oxidant effects Used for nitrogen transfer Kidney Acid-base regulation Releases ammonia in urine Combines with proton to release bicarbonate into renal venous bed Immune response Fuel for monocytes, macrophages, lymphocytes Unable to synthesise, rely on plasma glutamine Roles of Glutamine Over last 15-20 years effects of glutamine studied in ICU setting Beneficial effects including decreased morbidity/mortality Patients in ICU in profound catabolic states Release of amino acids from muscle breakdown Glutamine however does not increase in critically ill patients Decrease in plasma glutamine observed in critically ill patients Planas M, Schwartz S, Arbos MA, et al: Plasma glutamine levels in septic patients. JPEN J Parenter Enteral Nutr 1993; 17:299–300 Low glutamine has also been associated with increased mortality in ICU patients Oudemans-van Straaten HM, et al: Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001; 27:84–90 Not fully understood ?signalling molecule to regulate gene expression and intracellular signalling Stress signal to the body; increase cellular and immune defence Enhancement of Heat Shock Proteins These proteins are vital to cellular response to stresses, and regulate the management of intracellular proteins Wischmeyer etal. performed a series of experiments in a rat model to show that glutamine enhanced HSP-70 in septic rats Metabolic dysfunction was decreased ARDS decreased Decreased Mortality Ziegler TR etal. also went on to perform a pilot study; Double blind trial looking at Glutamine vs Isonitrogenous control solution in ICU patients on TPN for >5days Glutamine given as 0.5mg/kg*day Showed increase in HSP-70 expression Decrease in ICU stay Ziegler TR, Ogden LG, Singleton KD, et al: Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med 2005; 31:1079–1086 Activates peroxisome proliferation activated receptor-DNA binding sites This leads to attenuation of inflammatory response pathways through inhibitory transcription factors Glutamines acts on NF-kB signalling pathways ?HSP link, as HSP knockout mice loose this attenuation ability when glutamine administered after sepsis Glutamine decreases insulin resistance Reduced hyperglycaemia in ICU patients Enhances release of insulin from Beta-cells Overall improved insulin sensitivity after administration Dechelotte P, et al: L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: The French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34:598–604 Multiple advantages described to support glutamine administration Parenteral and enteral supplementation decrease mortality REDOXS study looking at glutamines ability to protect against injury, reduce inflammation, preserve metabolic function Critical Care Connections Inc 2005 (Canadian Clinical Practice Guidelines) suggest supplementation of parenteral nutrition with glutamine and enteral glutamine for burns/trauma patients Possible role in patient nutrition Possible role as prophylaxis in surgery/ICU for prolonged admissions