Nutrient Support in Critically Ill Children with ARF

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Nutrient Support in Critically Ill Children with
ARF

• NJ Maxvold MD
• Pediatric Critical Care Medicine
• DeVos Childrens Hospital
• Grand Rapids, MI, USA

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Nutrition in Pediatric ARF

• Critical Illness Metabolism
• Stress h Inflammatory Cytokines Gene
  Expression Modulation
• NeuroEndocrine Axis Phases
• Altered Substrate Utilization
• Metabolic Alterations in ARF
• h catabolism from uremia, acidosis, impaired
  fluid/solute K
• AA Profile / Interconversion in ARF
• Vitamin Derangements
• Impaired Lipolysis i Lipase Activity h LDL
  VLDL, i Cholesterol

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• Hyperglycemia of Critical Illness
• Altered Substrate Utilization in Acute Illness
• Carbohydrate Utilization
• a. Oxidation ( Inefficient)
• b.Glycogenesis
• c.Lipogenesis
• Insulin Resistance

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CHO Metabolism in Critical Illness

• Inefficient Glucose Metabolism
• Shift of Glycolysis to Pyruvate, then cycling
  back through the liver for Gluconeogenesis Cori
  Cycle
• Decrease Pyruvate entry into TCA cycle
• Therefore net energy produced is significantly
  diminished, and continues to feed into a
  hypermetabolic state of partial glucose oxidation
  then regeneration of Glucose High Glucose
  Turnover

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Van den Berghe G, et al. Crit care Med 2003
31359-366

• Normoglycemic Control 80-110 mg/dl
• i Crit Illness
• i Polyneuropathy
• i Bactermia
• i Inflammation
• i Anemia
• Reduction of Mortality

• Insulin Dose
• Preventive Effect on ARF
• Reduction of Mortality
• Prolonged Inflammation

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CHO Metabolism in Critical Illness

• Glycolysis
• Glucosegtgtgt 2 Lactate
• DG - 47.0 kcal/mol
• TCA Complete Oxidation
• Glucose 6 O2 a 6 CO2 6 H2O
• DG - 686.0 kcal/mol

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Metabolic Alterations in Critical Illness

• Lipid Utilization in Acute Illness
• Stress Hormones (Catecholamines/Cortisol) h
  Lipolysis FFA (major fuel in acute illness)
• a. Oxidation via TCA cycle
• b. Lipogenesis
• c. Ketogenesis (Glucagon inhibited during
  critical illness)
• d.PDH Inhibition (prevents Glucose TCA
  Oxidation and increases FFA TCA Oxidation)

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• Protein Metabolism in Acute Illness
• Catabolism (Skeletal Muscle)
• a. Gluconeogenesis (Alanine)
• b. Acute Phase Proteins (Liver Synthesis)
• Negative Nitrogen Balance

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Stress Liver synthetic Changes

• Anabolic
• Albumin, antithrombin,
• protein C
• High Density Lipoproteins

• Stress/Acute Phase
• Fibrinogen
• Ferritin,
• alpha-1antitrypsinogen
• anitiproteases

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Altered Cellular Metabolism

• Diminished Mitochondrial Energy Production
• Dysfunctional Respiration Downregulation of
  genes coding for electron transport chain
• Dysfunctional Glycolytic pathway
• Downregulation of gene for PFK (rate
  limiting enzyme)
• Callahan et al, J Appl
  Physiol 2005991120-1126

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Hypermetabolism in Children with Critical
Illness

• AveEnergy Intake
  REE
• Coss-Bu( Am J Clin Nutr 2001) 0.23 MJ/kg/d
  gt25
• Verhoeven(Int Care Med 1998) 0.24 MJ/kg/d
  gt14
• Joosten (Nutrition 1999) 0.26 MJ/kg/d
  gt20

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• Substrate Utilization/Nutrient Composition
• 75CHO15 AA 10 Lipid
• 15CHO 15AA 70 Lipid
• C13 Glucose, C13 Acetate
• Maximum Glu Oxidation 4mg/kg/min
• Lipogenesis from Excess Glucose Metabolism
• Gluconeogenesis and Protein Catabolism was not
  effected
• Tappy et
  al. Crit Care Med 199826860-867

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Protein Catabolism in ARF

• Adult Studies
• Protein Catabolic Rate 1.4 - 1.7 g/kg/d
• Macias WL, et al. JPEN
  19962056-62
• Chima CS, et al. JASN 1993
  31516-1521
• Pediatric Studies
• Urea Nitrogen Appearance 185- 290mg/kg/d
• Kuttnig M, et al. Child Nephrol Urol
  19911174-78
• Maxvold N, et al. Crit Care Med
  2000281161-1165

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Nitrogen Balance in ARF

• Bellomo R, et al. Ren Fail 199719111-120
• Protein Intake Nitrogen Balance
• 1.2 g/kg/d AA -5.5g N/d
• 2.5 g/kg/d AA -1.9g N/d
• Patients were on CRRT

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Conditional Essential Nutrients?

• Glutamine Nitrogen Trafficking
• Precursor of purine / pyridimine
• Substrate for Rapidly dividing Cells (Kidney
  tubular cells, enterocytes, immune cells)
• Precursor for Glutathione
• Substrate for Gluconeogenesis
• Intracellular Osmotic Regulator
• Primary Substrate for Ammoniagenesis(in Kidney
  and gut)

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Glutamine Metabolism

• Glutamine Release
• Muscle Free pool Gln
• Muscle protein catabolism
• Muscle synthesis of Gln

• Glutamine Uptake
• Gut Supply Dependent
• Liver, Spleen, Immune System Active, Independent

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Glutamine Metabolism

• Rested State
• Gln pl 500-600 micromol/L
• Gln Ms 15-20 mmol/L

• Catabolic State
• Rapid Fall in Gln pl
• gt30- 50 Muscle Gln Loss
• Reduced Muscle Resting Membrane Potential Defect
  Na electrochemical Gradient

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Glutamine Supplementation

• Ziegler et al, Ann Intern Med 1992116821
• 45 BMT patients with Parenteral Glutamine
  (L-Gln) Supplemention 0.57g/kg/d Gln
  2.07g/kg/d AA Intake
• Improved Nitrogen Balance -1.4g/d vs -4.2g/d
• i Clinical infections 3/24 vs 9/21
• Hospital stay 29 days vs 36 days
• Schloerb et al JPEN 1993 17407-413
• Hospital stay 26 days vs 32 days
• Total Body Water -1.2 L vs 2.2 L (Bioimpedance)

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Conditional Essential Nutrients?

• Biotin
• Regulatory Effect on genes of Intermediary
  Metabolism
• a. Stimulates genes for Insulin, Insulin
  Receptor, Glucokinase (pancreatic and Hepatic)
• b. Decreases gene expression of hepatic
  Phosphoenolpyruvate Carbosykinase (Gluconeogenic
  Enzyme in the liver)

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Conditional Essential Nutrients?

• Biotin Dose 15 mg/day
• i Hypertriglyceridemia in Type II Diabetics.
• Baez-Saldana et al. Am J Clin Nutr
  200478238-43
• i Glucose Concentration and Insulin
  Concentrations in Type II Diabetics.
• Fernandez-Mejia et al. Diabetes
  200352A459

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Nutrition in Pediatric ARF

• Amino Acids Alterations in ARF
• Impaired Conversion
• Phenylalanine to Tyrosine
• Citrulline to Arginine
• Homocysteine to Methionine
• Methionine to Cystine/Taurine
• Glycine to Serine

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Mitch WE, Chesney RW. Amino acid metabolism by
the kidney. Mineral Electrolyte Metab 9190-202
(1982)
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Druml W. Amino Acid Metabolism and Amino Acid
Supply in Acute Renal Failure. Continuous
Arteriovenous Hemofiltration (CAVH). Int Conf on
CAVH, Aachen1984, pp231-239.
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Amino Acid Effects in ARF

• Heyman SN, etal. Kidney Int
  199140273-9
• Gly, Ala Tubular protectant ischemic or
• nephrotoxic injury
• Wakabayashi Y, et al. Am J Physiol
  1996270F784-9
• Arg Preserves renal perfusion
• Singer P, et al. Clin Nutr
  19909(S)23A
• Badalamenti S, et al. Hepatology
  199011379-386
• AA Supplementation- h renal perfusion and GFR and
  diuresis

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Lipid Metabolism in ARF

• h LDL and VLDL
• iCholesterol and HDL-Cholesterol
• Impaired Lipolysis
• Lipase Activity 50
• i Lipoprotein Lipase
• i Hepatic Triglyceride Lipase

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Cholesterol Conditional Essential Nutrient in
ARF?

• Druml et al, Wien Klin Worchenschr
  2003115/21-22767-774
• Suppl free Cholesterol 4 g/l added to 20
  Lipid emulsions
• Results
• Reduced Plasma Triglycerides with reduced plasma
  ½ life and h total body clearance
• Fraction of Lipid Oxidation Improved

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Vitamins in Acute Renal Failure

• Water Soluble
• Vit B1 Def Altered Energy Metabolism,
• h Lactic Acid, Tubular damage
• Vit B6 Def Altered Amino acid and lipid
• metabolism
• Folate Def Anemia
• Vit C Def Limit 200 mg/d as precursor to
• Oxalic acid
  

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Vitamins in Acute Renal Failure

• Fat Soluble
• Vit D Def Hypocalcemia
• Vit A Excess i renal catabolism of
• retinol binding
  protein
• Vit E Def i gt50 plasma and RBC

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Nutrient Prescription in Pediatric ARF?

• Energy/Caloric Requirements 0.25 MJ/kg/d
• Formulation 20-25 Carbohydrate (Insulin as
  needed to keep Glu 100-140)
• Protein/AA 2-3 g/kg/d with Glutamine
  comprising 25-35
• Biotin Suppl of 10-15 mg/day
• Cholesterol ? 4 g/l/1.7m2/day
• Monitor REE, Nitrogen Balance, Vitamins and
  Trace Elements
• Early Enteral Feeding