glutamine in critical illness

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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. - PowerPoint PPT Presentation

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  • 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 sepsis230,000 deaths in the USA each year secondary to sepsisMortality rate from sepsis risen by 90% in last 20yearsDevelopment of multi-organ failureOrgan dysfunction secondary to shock, inflammation, metabolic disturbances

  • Non-essential amino acidMost abundant AA in the body50% free AA in plasmaEnergy sourcePrecursor to glutathioneFor nucleic acid synthesisAnti-oxidant effects Used for nitrogen transfer

  • KidneyAcid-base regulationReleases ammonia in urineCombines with proton to release bicarbonate into renal venous bedImmune responseFuel for monocytes, macrophages, lymphocytesUnable to synthesise, rely on plasma glutamine

  • Over last 15-20 years effects of glutamine studied in ICU settingBeneficial effects including decreased morbidity/mortalityPatients in ICU in profound catabolic statesRelease of amino acids from muscle breakdownGlutamine however does not increase in critically ill patients

  • Decrease in plasma glutamine observed in critically ill patientsPlanas M, Schwartz S, Arbos MA, et al: Plasma glutamine levels in septic patients. JPEN J Parenter Enteral Nutr 1993; 17:299300Low glutamine has also been associated with increased mortality in ICU patientsOudemans-van Straaten HM, et al: Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001; 27:8490

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

  • Enhancement of Heat Shock ProteinsThese proteins are vital to cellular response to stresses, and regulate the management of intracellular proteinsWischmeyer etal. performed a series of experiments in a rat model to show that glutamine enhanced HSP-70 in septic ratsMetabolic dysfunction was decreasedARDS 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 >5daysGlutamine given as 0.5mg/kg*dayShowed increase in HSP-70 expressionDecrease 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; 31:10791086

  • Activates peroxisome proliferation activated receptor-DNA binding sitesThis leads to attenuation of inflammatory response pathways through inhibitory transcription factorsGlutamines acts on NF-kB signalling pathways?HSP link, as HSP knockout mice loose this attenuation ability when glutamine administered after sepsis

  • Glutamine decreases insulin resistanceReduced hyperglycaemia in ICU patientsEnhances release of insulin from Beta-cellsOverall 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; 34:598604

  • Multiple advantages described to support glutamine administrationParenteral and enteral supplementation decrease mortalityREDOXS 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 patientsPossible role in patient nutritionPossible role as prophylaxis in surgery/ICU for prolonged admissions

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