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Glutamine in Critical Illness

Shiva Sharma SHO Breast/Endocrine Surgery. Glutamine in Critical Illness. Contents. Introduction Roles of Glutamine in the body Tissue Protection Anti-inflammatory regulation Preservation of metabolic function Glutamine as therapy.

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Glutamine in Critical Illness

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  1. Shiva Sharma SHO Breast/Endocrine Surgery Glutamine in Critical Illness

  2. Contents • Introduction • Roles of Glutamine in the body • Tissue Protection • Anti-inflammatory regulation • Preservation of metabolic function • Glutamine as therapy

  3. 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

  4. What is Glutamine? • 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

  5. Roles • 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

  6. Roles of Glutamine

  7. Glutamine in Critical Illness • 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

  8. 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

  9. Mechanism • Not fully understood • ?signalling molecule to regulate gene expression and intracellular signalling • Stress signal to the body; increase cellular and immune defence

  10. Tissue Protection • 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

  11. 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

  12. Anti-Inflammatory Regulation • 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

  13. Metabolic Function • 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

  14. Glutamine as a Therapy • 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

  15. 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

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