Nutrition support in the ICU setting

1. Nutrition support in the ICU setting It is what you don’t see that really matters

5. nucleus • oxygen • macronutrients • micronutrients • substrates • hormones • cytokines • CO2 • breakdown products • micronutrients • substrates • hormones • cytokines • energy production • substrate utilization • substrate synthesis • protein / complex subs synthesis LOCAL EFFECTS Endothelium interaction • Interaction with clotting mechanism • interaction with inflammation process SYSTEMIC EFFECTS Capillary arterial side Capillary venous side The microcirculatory environment

7. DNA Stimulus • nutrient • microbe • cell debris • physical agent • chemical agent • hostile environment PROTEIN SYNTHESIS Response • defense • offense • repair • suicide Current Concept Stimulus and cell response

8. Amino Acids Glycerol Diet Intestine Liver Lactate Plasma glucose 70 mg/dL (3.9 mmol/L Kidney Muscle and other tissues Brain Fat Urine (when plasma glucose > 180mg/dL) Glucose homeostasis

9. Stomach MCT • Liver (remnant receptor) • LDL Receptor • HDL Receptor Diet Intestine Bile acids LDL B-100 Plasma Chylomicron remnants E, B48 Lymphatics IDL B-100 LPL Plasma Chylomicrons E, C, & B48 , FFA (bound to albumin) LPL Plasma LCAT VLDL E, C, B-100 HDL LDL Receptor Muscle and other tissues Lipid metabolism

10. Inert protein (hair, etc) Body protein Diet transamination Common metabolic pool Amino acid pool Urinary excretion amination deamination Creatine NH4 Hormones Neurotransmitters Purines, pyrimidines Urea Protein metabolism

11. Lecuit M, Sonnenburg J. Host-microbial relationship in the intestine: sensing commensal and pathogenic bacteria: Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 Host-microbial interaction

12. Lecuit M, Sonnenburg J. Host-microbial relationship in the intestine: sensing commensal and pathogenic bacteria: Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 Host-microbial recognition

13. Gut – inductive and effector sites Per Brandtzaeg, Mucosal adaptive immunity: impact of exogenous stimuli and feeding; Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005

14. Cell mediated immunity, graft rejection, chronic inflammation IgG2a Macrophage CTL NK cell B cell IL-2, IFN Antigen Th 1 IL-12 IL-2, IFN + + Antigen presenting cell Th 0 Naïve Th cell - - + Th 2 IL-2 Eosinophil IL-4 IL-4 Allergic inflammation Mast cell B cell IgE IgG1

15. microbes tissue antigens tissue injury B B IgG IgM IgE trigger N Mast cell C3a C5a Complement Activation T M Inflammatory mediators migration permeability adhesion Endothelial vessel M T N The immune system in acute inflammation

16. Cardiac function Pulmonary function Intake • Microcirculation environment • extracellullar • intracellular FOOD Energy provision Protein synthesis Renal function Carbohydrates, fats, protein, electrolytes, trace elements, vitamins, special substrates Body reserves (malnourished) Body reserves (adequate fed) Nutrition and microcirculation

17. cytochrome • dehydrogenase Oxidation Energy Iron Protein synthesis Wound healing Zinc • DNA processes Copper • SO dismutase Immunity Phagocytosis Selenium • Glutathione Antioxidants Inflammation Trace elements and life processes

18. Dietary nucleotides DNA mRNA digestion  Adenylate charge  Ap4A Nucleosides Modification of nucleotide pool Bases CD antigens • specific proteins • cytokines Protein synthesis Cytokines Response Enterocyte or Gut Lymphocyte Gil A, Modulation of the immune response mediated by dietary nucleotides. Eur J Clin Nutr, 2002 Nucleotides: cellular mechanics

19. Tissue inflammation, Early organ failure and death SIRS TNF, IL-1, IL-6, IL-12, IFN, IL-3 PRO days weeks Inflammatory balance ANTI IL-10, IL-4, IL-1ra, Monocyte HLA-DR suppression Immunosuppression Delayed MOF and death 2nd Infections CARS Insult (trauma, sepsis) Griffiths, R. “Specialized nutrition support in the critically ill: For whom and when? Clinical Nutrition: Early Intervention; Nestle Nutrition Workshop Series Inflammation and organ failure in the ICU

20. Calder Philip, Polyunsaturated fatty acids, inflammation, and immunity : Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 EPA NFB Arachidonic acid in membrane phospholipids DHA Phospholipase A2 Inflammatory effects (e.g. cytokines) Free arachidonic acid COX-2 5-LOX 5-LOX COX-2 COX-2 E-series resolvins 3-series PG & TX 5-series LT 2-series PG & TX 4-series LT D-series resolvins, etc Anti Inflammatory effects Inflammatory effects Less Inflammatory effects than 4-series Less Inflammatory effects than 2-series Anti Inflammatory effects Anti Inflammatory effects Inflammatory effects -3 PUFA

21. Principal areas to address • Adequacy of microcirculation: • Accurate fluid balance • Adequate oxygenation • Adequacy of nutrients (macro and micro) • Appropriate access • Accurate calorie count • Differentiation between infection and SIRS • Appropriate antibiotic use

22. Nutrition issues in critical care • Adequate and complete nutrient intakes • “NPO” mind set • Type of nutrient and route of delivery • Development of immune reactions (e.g. allergy) • Parenteral nutrition • Antibiotics • Effect on normal flora • Preventive measures • Stressful or injurious environment (e.g. oxidative stress) • Use of special nutrients that become conditionally essential

24. Who are these patients? “Group A” • Inadequate intake due to multiple etiologies • Chronic illness • Cardiac problems • Pulmonary problems • Gastrointestinal problems • Stroke • Depressed • Geriatric patients • Common Features: • No appetite • Swallowing problems • Malabsorption

25. HOW ABOUT CANCER PATIENTS? Stage 3-4 “Group B”

26. Group “A” & “B” patients 20% energy (keys) Complete starvation Injury + Starvation 0 Decision Box 5 Maastricht trial 1992 10 Veterans trial 1990 15 Nottingham trial 1983 20 Lincoping trial 1990 Studley 1930 % WEIGHT LOSS 25 Keys 1953 30 Warsaw Ghetto 1942 35 30% Mortality 40 45 DAYS 0 10 20 30 40 50 60 70 80 90 100 Allison SP. The uses and limitations of nutrition support. Arvid Wretlind lecture given at 14th ESPEN Congress in Vienna. Clinical Nutrition (1992) 11: 319-330.

27. Ability to withstand starvation - effects of age and size 2500 2000 2 kg prem adult 1500 Calorie reserve (kcal/kg) term 1000 1 year old 500 1 kg prem 0 10 20 30 40 50 60 70 80 90 100 Duration of starvation (days) Pediatric patients: Priorities

28. 200 Lymphoid type 180 Neural type 160 140 General type 120 Percent Genital type 100 80 60 40 20 B 2 4 6 8 10 12 14 16 18 20 Age in years Pediatric patients: Priorities • Brain growth is pre-programmed; especially high in the first 2 years • Myelinization is completed by 6 to 12 months and in some nerves up to 2 years

29. gluconeogenesis protein loss high carbo used up in 48 hrs Fat use diverted Energy reserves utilization – critically ill

31. Alternate pathway activators: C3bBb C4b2a C3 Classical pathway activators C4 C3a C4a C1qr2s2 C1qr2s2 C3b B C4b C2 MBL MASP1, MASP2 MBL MASP1, MASP2 C3bB C4b2 D Ba C3 C2b Lectin pathway activators C3bBb C4b2a C3a C3b C8 C9 C6 C7 C5 C5b C5a C3b C5b-9 C5b67 Surface site Complement System

32. Alternate pathway activators: C3bBb C4b2a C3 Classical pathway activators C4 C3a C4a C1qr2s2 C1qr2s2 C3b B C4b C2 MBL MASP1, MASP2 MBL MASP1, MASP2 C3bB C4b2 D Ba C3 C2b Lectin pathway activators C3bBb C4b2a C3a C3b C8 C9 C6 C7 C5 C5b C5a C3b C5b-9 C5b67 Surface site Complement System Antigen/ antibody complexes (adaptive Microorganisms (innate)

33. How the Complement System Works

34. Current update