TPN and lipid. RCT of 57 patients. TPN with lipid vs TPN without lipid. TPN associated with increased infectious complications

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1 TPN and lipid RCT of 57 patients TPN with lipid vs TPN without lipid TPN associated with increased infectious complications * * * * Battistella FD, et al. J Trauma 1997; 43:52.

2 Data Needed 1. New TPN trials with glucose control 2. New trials withholding lipids or utilizing Omega -3 lipids 3. Omega-3 lipid administration as a separate pharmacologic supplement

3 Outline Topics for Research in Clinical Nutrition! Glucose Control/Caloric Intake! Proper delivery of TPN! Pharmaconutrients! Pharmaconutrients: : Omega-3 Fats - the age of nutrigenomics is upon us! Pharamaconutrients: : Glutamine! Pharamaconutrients: Arginine! Perioperative Nutritional Intervention

4 Modulating inflammatory and oxidative stress with nutrients: The effect of aging

5 Aging is associated with an increase in signs of inflammation and oxidatative stress and reduction in cell mediated immunity Increased cytokine production Loss of muscle and bone Increased blood lipids Inflammatory & Oxidative Increased amount of disease with an inflammatory component in its cause. Increased Stress Impaired cell mediated immunity

6 Increase in fasting plasma triglycerides and C-Reactive protein with age in healthy Caucasian men Fasting triglyceride Fasting C-reactive protein Age group n= n= Significant effect of age grouping p< Kruskal-Wallis Test

7 IL pro-inflammatory SNP (T) related to 3-year mortality in elderly male geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 Cumulative Proportion Surviving 1,0 Non-infl (CC) Pro-infl (CT+TT) P=0.02 0, Months Cederholm et al J. Intern Med 2007; 262:

8 Investigation of whether the genotype for pro-inflammatory cytokines influences the outcome of hospitalised elderly subjects.

9 Subjects 79 patients consecutively admitted to two geriatric wards were studied 83±7 years, 68% females Chronic illness/exacerbation, infections, fall trauma Median hospital stay 11 ( th-75th perc) days

10 TNF!-308 pro-inflammatory SNP (A2) improves survival in elderly female geriatric patients 1,0 Cumulative Proportion Surviving 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 TNF12 Pro-infl (A1A2) Non-infl (A1A1) TNF11 P= ,1 0, Months Grimble et al Clin Nutr 2003;22:S39

11 IL pro-inflammatory genotype (GG) improves 3-year survival in elderly female geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 Cumulative Proportion Surviving 1,0 Non-infl (CC+CG) Pro-infl (GG) P=0.02 P= ,1 0, Months Grimble et al Clin Nutr 2003;22:S39

12 TNF"+252 pro-inflammatory genotype (B22) decreases 3- year survival in elderly male geriatric patients 1,0 Cumulative Proportion Surviving 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 TNFB22 Non-infl (B11, B12) Pro-infl (B22) P=0.04 Grimble et al Clin Nutr 2003;22:S39 0, Months

13 IL pro-inflammatory SNP (T) decreases 3-year survival in elderly male geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 Cumulative Proportion Surviving 1,0 Non-infl (CC) Pro-infl (CT+TT) P=0.02 Grimble et al Clin Nutr 2003;22:S39 0, Months

14 Modulating inflammatory and oxidative stress with nutrients. The effect of aging.

15 Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells

16 Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells Oxidants Pathogen killing Tissue damage Hostile environment

17 Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells Oxidants Pathogen killing Tissue damage Nutrient release from host tissues Hostile environment Appetite loss

18 Trauma/infection/burns Pro-inflammatory cytokines Immune system activation Immunonutrition T and B cells Oxidants Antioxidant defence Glucose Pathogen killing Hostile environment Tissue damage - Nutrient release from host tissues Appetite loss Sulphur amino acids Glutamine Glutathione synthesis Antioxidant defences strengthened

19 Trauma/infection/burns Pro-inflammatory cytokines Oxidants Antioxidant defence Immune system activation - Feedback systems IL10, Heat shock proteins Glucose Immunonutrition T and B cells Pathogen killing Hostile environment Tissue damage - Nutrient release from host tissues Appetite loss Sulphur amino acids Glutamine Glutathione synthesis Antioxidant defences strengthened

20 Take home messages "Inflammatory and oxidative stress increase with aging. "Plasma lipids and endothelial dysfunction increase with age. "The lipid lowering, anti-inflammatory effects of fish oil are more likely to occur in old than young subjects. "These effects in old subjects are more likely in individuals with a pro-inflammatory genotype.

21 You Are What You Eat Dietary!-6 FA Membrane phospholipids Dietary!-3 FA Arachidonic acid Eicosapentaenoic acid Docosahexaenoic acid lipoxygenase cyclooxygenase lipoxygenase Leukotrienes (4 series) Proinflammatory Cell adhesive Chemotactic Prostanoids & Thromboxanes (2 series) Aggregates platelets Immunosuppressive Prostanoids & Thromboxanes (3 series) Antiaggregatory Non-immunosuppressive Leukotrienes (5 series) Anti-inflammatory Nonadhesive

22 Enteral Nutrition With Eicosapentaenoic Acid (EPA),!-Linonenic Acid (GLA) and Antioxidants in Critical Illness: : A Meta- Analysis Evaluation of Outcome Data Pontes-Arruda A, DeMichele S, Seth A and Singer P Crit Care Med 34 (12 Suppl 1): A95, 2006

23 Enteral Nutrition With Eicosapentaenoic Acid (EPA),!-Linonenic Acid (GLA) and Antioxidants in Critical Illness: : A Meta- Analysis Evaluation of Outcome Data Pontes-Arruda A, DeMichele S, Seth A and Singer P Crit Care Med 34 (12 Suppl 1): A95, 2006

24 Study name Statistics for each study Std diff in means and 95% CI Std diff Standard Lower Upper Relative in means error Variance limit limit Z-Value p-value weight Pontes-Arruda et al, Singer et al, Gadek et al, Fixed effects MORE ICU-FREE DAYS p < Favors Control Favors EPA+GLA Pontes-Arruda et al. Crit Care Med 34:A95, 2006

25 Study name Statistics for each study Std diff in means and 95% CI Pontes-Arruda et al, 2006 Std diff Standard Lower Upper Relative in means error Variance limit limit Z-Value p-value weight Singer et al, Gadek et al, Fixed effects Favors Control Favors EPA+GLA MORE VENTILATOR-FREE DAYS p < Pontes-Arruda et al. Crit Care Med 34:A95, 2006

26 Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper Relative ratio limit limit Z-Valuep-Value weight Pontes-Arruda et al, Gadek et al, Fixed effects Favors EPA+GLA Favors Control 83% LESS ORGAN FAILURES p < Pontes-Arruda et al. Crit Care Med 34:A95, 2006

27 28-Days All Cause Mortality Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper Relative Oxepa ratio limit limit Z-Valuep-Value weight (n/n) Control (n/n) Pontes-Arruda et al, /55 25/48 Singer et al, Gadek et al, /46 28/49 6/51 9/47 Fixed effects % Reduction p = FAVORS EPA/GLA FAVORS CONTROL ITT Mortality (All 411 Patients) 49% Reduction p = (OR %CI: ) Pontes-Arruda et al. Crit Care Med 34:A95, 2006

28 Would Parenteral Omega-3 lipids have even better effects??

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