Shiva SharmaSHO Breast/Endocrine Surgery

IntroductionRoles of Glutamine in the bodyTissue ProtectionAnti-inflammatory regulationPreservation of metabolic functionGlutamine as therapy

Leading cause of death in critically ill patients is sepsis 230,000 deaths in the USA each year

secondary to sepsisMortality rate from sepsis risen by

90% in last 20yearsDevelopment of multi-organ failure

Organ dysfunction secondary to shock, inflammation, metabolic disturbances

Non-essential amino acidMost abundant AA in the body

50% free AA in plasmaEnergy sourcePrecursor 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

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