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Pharmaconutrition: Selected Nutrients and Their Influence on Patient Outcomes The Canadian Clinical Practice Guidelines

Pharmaconutrition: Selected Nutrients and Their Influence on Patient Outcomes The Canadian Clinical Practice Guidelines. Daren K. Heyland, MD, FRCPC, MSc. Queen’s University, Kingston, Ontario. Updated July 2006 . www.criticalcarenutrition.com. Immunonutrition: Cocktail Approach?.

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Pharmaconutrition: Selected Nutrients and Their Influence on Patient Outcomes The Canadian Clinical Practice Guidelines

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  1. Pharmaconutrition: Selected Nutrients and Their Influence on Patient OutcomesThe Canadian Clinical Practice Guidelines Daren K. Heyland, MD, FRCPC, MSc Queen’s University, Kingston, Ontario

  2. Updated July 2006 www.criticalcarenutrition.com

  3. Immunonutrition: Cocktail Approach? • Specific nutrients found to have effects on immune system, metabolism, and GI structure and function • Arginine • Glutamine • Omega-3 fatty acids • Nucleic acids • others • Individual effect on clinical outcomes?

  4. endothelial dysfunction activation of coagulation/complement Insult • infection • trauma • I/R • hypoxemic/ • hypotensive Activation of PMN’s elaboration of cytokines, NO, and other mediators generation of OFR (ROS + RNOS) Role of GIT mitochondrial dysfunction oxidative stress = cellular = energetic failure Death organ = failure Pathophysiology of Critical Illness Key nutrient deficiencies (e.g. glutamine, selenium) Arginine

  5. Elective Surgical Patient • cellular immune dysfunction • T-cell • decrease cytokine activation • IL-2, IFN

  6. Elective Surgical Patient arginase arginine expression of zeta chain Taheri Clin Cancer Res 2001 ;7:958

  7. =

  8. 1.18 (0.88,1.58)

  9. Which Nutrients? Which Patients? Population Nutrients Canadian Clinical Practice Guidelines JPEN 2003;27:355 www.criticalcarenutrition.com

  10. Underlying Rationale for Framework • No scientific rationale for combining nutrients together; need to consider them alone • Empirical evidence that the nutrients have different treatment effects across populations

  11. Which Nutrient for Which Population? Population Nutrients Canadian Clinical Practice Guidelines JPEN 2003;27:355

  12. Arginine-supplemented diets?

  13. Underlying PathophysiologyRole of Nitric Oxide Mitaka Shock 2003;19: 305

  14. Optimal NO-Balance cNOS - Microcirculation- Immune augmentation  Benefitial Effect of Arginine induced NO formation Arginine / NO availability Harmful cNOS + iNOS - Hemodynamic instability- Immune Suppression- Cytotoxicity- Organe dysfunction Suchner Brit J Nutrition 2001

  15. Effect of Arginine-supplemented diets on Mortality www.criticalcarenutrition.com

  16. Effect of Arginine-supplemented diets on Infectious complications www.criticalcarenutrition.com

  17. Effect of Arginine-supplemented diets in Critically Ill Patients • Possible mortality in septic pts. Crit Care Med 1995;23:436 Dent, Crit Care Med 2003 Bertolini Int Care Med 2003;29:834 •  cost. • Lack of treatment effect. But what about ...

  18. Glutamine supplementation?

  19. Potential Beneficial Effects of Glutamine Enhanced Heat Shock Protein GLN Pool Enhanced insulin sensitivity Decreased Free Radical availability (Anti-inflammatory action) NF-B ? Inflammatory Cytokine Attenuation Glutathione Synthesis Glutamine Therapy Reduced Translocation Enteric Bacteria or Endotoxins Maintenance of Intestinal Mucosal Barrier Fuel for Enterocytes Critical Illness Nuclotide Synthesis Preservation of TCA Function Reduction of Infectious complications Maintenance of Lymphocyte Function Fuel for Lymphocytes Anti-catabolic effect Preserved Cellular Energetics- ATP content Preservation of Muscle mass GLN pool

  20. Effect of Glutamine: A Systematic Review of the Literature Infectious Complications www.criticalcarenutrition.com

  21. Effect of Glutamine: A Systematic Review of the Literature Mortality www.criticalcarenutrition.com

  22. Results of subgroup analysis EN vs PN?

  23. Benefit of Parenteral Glutamine in Patients on EN?

  24. Fish Oil supplemented diets?

  25. Mechanisms of Action • Mediator formation depends on the phospholipid fatty acid content of arachidonic acid (AA) in inflammatory cell membranes • It is possible to modulate the content of AA in inflammatory cell membranes by changing lipid composition of the diet

  26. Mechanisms of Action GLA EPA Arachidonic Acid Borage Oil Fish Oil CyclooxygenaseLipoxygenase DGLA Substitution of AA By EPA Resulting in: Substitution of AA By DGLA resulting in: Decrease in Pro-Inflammatory Eicosanoids (LTB4, TXA2, PGE2) Less Inflammatory Eicosanoids (TXA3, PGE3, LTB5) PGE1 and Less Inflammatory Eicosanoids

  27. Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI • RCT of 146 critically ill patients with ALI and BAL+ for WBCs • Double-blinded; ITT • Experimental: Oxepa® • Control: high fat diet • Groups well matched at baseline P=0.02 P=0.03 P=0.17 Gadek Crit Care Med 1999;27:1409

  28. Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI • RCT of 100 critically ill patients with ALI • Single center • unblinded; not ITT • Experimental: Oxepa® • Control: high fat diet • Oxepa associated with improved oxygenation and lung compliance Singer Crit Care Med 2006:34;1033

  29. Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI • RCT of 165 critically ill patients with ARDS secondary to sepsis • Double-blinded; not ITT • Experimental: Oxepa® • Control: high fat diet • Oxepa associated with: • improved oxygenation • More Vent free days • More ICU free days • Fewer new organ failures P=0.04 Pontes -Arruda Crit Care Med 2006:34;2345

  30. Overall Effect on Mortality www.criticalcarenutrition.com

  31. Interpretation of Studies? • treatment effect of antioxidants? • treatment effect of borage oils? • comparison to standard enteral feeding products? How do you interpret the findings?

  32. Antioxidant-supplemented specialized diets?

  33. Rationale for Antioxidants Infection InflammationIschemia OFR CONSUMPTION OFR PRODUCTION Depletion of Antioxidant Enzymes OFR Scavengers Vitamins/Cofactors Impaired - organ function - immune function - mucosal barrier function OXIDATIVE STRESS OFR production > OFR consumption = Complications and Death

  34. Rationale for Antioxidants • Endogenous antioxidant defense mechanisms • Enzymes (superoxide dismutase, catalase, glutathione perioxidase, glutathione reductase including their cofactors Zn and Selenium) • Sulfhydryl group donors (glutathione) • Vitamins E, C, and B-carotene

  35. Rationale for Antioxidants

  36. Effect of Combined Antioxidant Strategies in the Critically Ill Effect on Mortality

  37. Which Nutrient for Which Population? Population Nutrients Canadian Clinical Practice Guidelines JPEN 2003;27:355

  38. REducing Deaths from OXidative Stress:The REDOXS study antioxidants Factorial 2x2 design glutamine R Concealed Stratified by 1200 ICU patients R placebo Evidence of • site organ failure antioxidants • Shock R placebo placebo

  39. Critical Care Nutrition Web Site www.criticalcarenutrition.com • web based clinical practice guidelines • summaries of evidence • online survey of current practice • benchmarking (other sites and the clinical practice guidelines) • tools (protocols, etc) • research related news

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