Presentation on theme: "Arginine: Friend or Foe"— Presentation transcript:
1Arginine: Friend or Foe Juan B. Ochoa, MD, FACSProfessor of Surgery and Critical CareMedical Director Division of Trauma SurgeryUniversity of Pittsburgh
2DisclosuresUniversity of PittsburghFinancial SupportNIH – K , RO1 GM065914Pittsburgh Society FoundationNutrition CompaniesRoss, Novartis, NestlePatentArginase and Immunity
3Objectives Review the metabolism of arginine Demonstrate how disease alters the expression of the metabolic pathways.TraumaSepsisDetermine possible biological rolesIn healthIn diseaseEvaluate the clinical role of arginine supplementation.
4Arginine Supplementation Biologically active MetabolitePhysiological ChangeBenefit
5Arginine Supplementation Biologically active MetabolitePathological ChangeDetriment
6Arginine Intestinal Lumen Citrulline Citrulline Protein Breakdown GlutamineCitrullineArginineProtein Breakdown
8Arginine - Vasodilation Nitric oxide Generated by aCONSTITUTIVE ENZYMEVery small quantitiesSubstrate DependentThe more arginine, the more vasodilationBetter Organ PerfusionMore tolerance to low flow states - SHOCK
9Effect of Arginine on Microcirculation after Open Heart Surgery Tepaske - Lancet 2001 Circulating NOx was Increased
10The effect of Arginine infusion on Nitric oxide Production in ischemic flaps 8 Pigs - Vascularized Pedicle Ischemic Flaps. Arginine given DURING the creation of the FlapNitric oxide production measured by chemiluminescence – microdialysisFlap viability using vital dyes
11Arginine and Immunity 1980’s – Arginine incorporated into so called “Immune Enhancing Diets”Other Nutrients addedOmega 3 Fatty acidsNucleotides“Boost” the Immune System
12Arginine and Immunity Friend or Foe? Benefit: “Enhanced” immunity “better” fights against infectionHarm: “Enhanced” immunity may produce “Self Injury”
13What is the Evidence? Harm vs. Benefit Under Resting conditionsArginine is NOT used by the immune SystemNO mechanism of arginine transport into the cell.Enzymes that metabolize arginine NOT expressed.Therefore there is NO EVIDENCE that arginineIs an “IMMUNE ENHANCER”Dr. Bobbi Langkamp-Henken
22Relationship between plasma arginine and leucine after trauma and sepsis.
23Arginine Deficiency after Trauma Caused by Increased ArginaseNote: arginase expression may be modulated by omega 3 fatty acidsIs difficult to overcome with arginine replacement aloneHigh doses of arginineArginine homeostasis is restored by a combination ofArginineOmega 3 Fatty AcidsNucleotides?
24No Clear Evidence of Arginine Deficiency in Sepsis
25What about Clinical Evidence of Benefit or Harm?
26Meta-analysis- Immune Enhancing Diets and Infectious Complications Heyland D. JAMA 2001;(286)8:Taken as a whole indiscriminate use of IEDs is NOT indicated.IEDs ONLY work on disease processes where there is arginine DEFICIENCYThe Heyland meta-analysis looked at studies where the products had supplemental arginine as well as fish oil.This shows you how the immune restoring diets faired when compared to standard enteral diets in both elective surgery and critically ill patients.There’s a couple of take away points I want to leave you with here.#1, this data shows a clear indication for the use of high arginine diets in elective surgery and trauma patients.#2, this data has increased our awareness for the need to further study the application of these diets in septic patients.#3, if we are to meaningfully discuss and study the use of immune restoring diets in our patients we must drop the concept of ‘critical illness diet’ and talk specifically about surgery, trauma, and sepsis. Given what we know about arginine metabolism, critical illness is no longer a very useful term in discussing patient populations and the best diet to put them on.
27Trauma/SurgeryHemolytic DiseasesSickle Cell AnemiaArginine DeficiencyCancerTransfusionsChronic InfectionsHypertension of Pregnancy
28Conclusions Arginine is Not an Immune Enhancer Arginine is metabolized in a completely different way in health and diseaseChanges in arginine metabolism occur principally in the immune systemTrauma activates Myeloid cells to produce arginaseArginase depletes arginine & generates ornithineSepsis appears NOT to be associated with arginine deficiency
29Conclusions Clinical Evidence Surgery is benefited by the use of arginine, omega 3 fatty acids, and nucleotidesIdeally used 5 days preoperativelyOverall > 20 clinical Studies↓ 40% in infection ratesSignificant savingsTrauma Patients appear to benefit alsoModest number of patients
30Conclusions Medical Critically Ill Patients are NOT benefited. No clear evidence of HarmSepsis Patients Controversial evidenceSome studies show HarmSome studies show benefitArginine-containing diets SHOULD NOT be used in these Patients
31The Benefit or Harm of Arginine depends on How we use it Thank you ASPEN