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 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