Transcript Z06-Maxwold Norma Nutri - Pediatric Continuous Renal

Nutrient Support in Critically Ill
Children with ARF
NJ Maxvold MD
Pediatric Critical Care Medicine
DeVos Children’s Hospital
Grand Rapids, MI, USA
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
“ Hyperglycemia” of Critical Illness
• Altered Substrate Utilization in Acute Illness
Carbohydrate Utilization:
a. Oxidation ( Inefficient)
b.Glycogenesis
c.Lipogenesis
Insulin Resistance
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}
[Van den Berghe G, et al. Crit care Med
2003; 31:359-366]
Normoglycemic Control [80110 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
CHO Metabolism in Critical
Illness
•
Glycolysis:
Glucose>>> 2 Lactate
DG°´= - 47.0 kcal/mol
TCA Complete Oxidation:
Glucose + 6 O2 a 6 CO2 + 6 H2O
DG°´= - 686.0 kcal/mol
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)
• Protein Metabolism in Acute Illness
Catabolism (Skeletal Muscle)
a. Gluconeogenesis (Alanine)
b. Acute Phase Proteins (Liver Synthesis)
“Negative Nitrogen Balance”
Stress Liver synthetic Changes
• Anabolic :
• Albumin,
antithrombin,
• protein C
• High Density
Lipoproteins
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Stress/Acute Phase:
Fibrinogen
Ferritin,
alpha-1antitrypsinogen
anitiproteases
Altered Cellular Metabolism
•
Diminished Mitochondrial Energy
Production:
I.
Dysfunctional Respiration: Downregulation of
genes coding for electron transport chain
Dysfunctional Glycolytic pathway:
Downregulation of gene for PFK (rate limiting
enzyme)
II.
[Callahan et al, J Appl Physiol 2005;99:1120-1126]
Hypermetabolism in Children
with Critical Illness
AveEnergy Intake REE
Coss-Bu( Am J Clin Nutr 2001)
0.23 MJ/kg/d
>25%
Verhoeven(Int Care Med 1998) 0.24 MJ/kg/d
>14%
Joosten (Nutrition 1999)
>20%
0.26 MJ/kg/d
•
Substrate Utilization/Nutrient Composition
75%CHO:15% AA: 10% Lipid
15%CHO: 15%AA: 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 1998;26:860-867]
Protein Catabolism in ARF
• Adult Studies:
• Protein Catabolic Rate ~ 1.4 - 1.7 g/kg/d
[Macias WL, et al. JPEN 1996;20:56-62]
[Chima CS, et al. JASN 1993; 3:1516-1521]
Pediatric Studies:
Urea Nitrogen Appearance ~ 185290mg/kg/d
[ Kuttnig M, et al. Child Nephrol Urol 1991;11:74-78]
[ Maxvold N, et al. Crit Care Med 2000;28:1161-1165]
Nitrogen Balance in ARF
[Bellomo R, et al. Ren Fail 1997;19:111-120]
Protein Intake :
• 1.2 g/kg/d AA
• 2.5 g/kg/d AA
Nitrogen Balance
-5.5g N/d
-1.9g N/d
* Patients were on CRRT
Conditional” Essential Nutrients?
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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)
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]
Glutamine Metabolism
• Rested State:
• Gln [pl] ~500-600
micromol/L
• Gln [Ms] ~15-20
mmol/L
• Catabolic State:
• Rapid Fall in Gln [pl]
• >30- 50% Muscle Gln
Loss
• Reduced Muscle
Resting Membrane
Potential [Defect Na+
electrochemical
Gradient]
Glutamine Supplementation
[Ziegler et al, Ann Intern Med 1992;116:821]
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
i Clinical infections: 3/24 vs 9/21
i Hospital stay: 29 days vs 36 days
-4.2g/d
[ Schloerb et al; JPEN 1993; 17:407-413]
i Hospital stay:
26 days vs 32 days
i Total Body Water: -1.2 L vs 2.2 L (Bioimpedance)
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)
Conditional” Essential Nutrients?
Biotin Dose 15 mg/day
i Hypertriglyceridemia in Type II Diabetics.
[Baez-Saldana et al. Am J Clin Nutr 2004;78:238-43]
i
Glucose Concentration and Insulin
Concentrations in Type II Diabetics.
[ Fernandez-Mejia et al. Diabetes 2003;52:A459]
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
Mitch WE, Chesney RW. Amino acid metabolism by the kidney. Mineral
Electrolyte Metab 9:190-202 (1982)
Druml W. Amino Acid Metabolism and Amino Acid Supply in Acute Renal
Failure. Continuous Arteriovenous Hemofiltration (CAVH).
Int Conf on CAVH, Aachen1984, pp231-239.
Amino Acid Effects in ARF
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Heyman SN, etal. Kidney Int 1991;40:273-9
• Gly, Ala
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Wakabayashi Y, et al. Am J Physiol 1996;270:F784-9
• Arg
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Tubular protectant [ischemic or
nephrotoxic injury]
Preserves renal perfusion
Singer P, et al. Clin Nutr 1990;9(S):23A
Badalamenti S, et al. Hepatology 1990;11:379-386
AA Supplementation- h renal perfusion and GFR
and diuresis
Lipid Metabolism in ARF
• h LDL and VLDL
• iCholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity ~50%
i Lipoprotein Lipase
i Hepatic Triglyceride Lipase
Cholesterol: Conditional
Essential Nutrient in ARF?
• [Druml et al, Wien Klin Worchenschr 2003;115/21-22:767774]
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
Vitamins in Acute Renal Failure
• Vit B1 Def
• Vit B6 Def
• Folate Def
• Vit C Def
Water Soluble
Altered Energy Metabolism,
h Lactic Acid, Tubular damage
Altered Amino acid and lipid
metabolism
Anemia
Limit 200 mg/d as precursor to
Oxalic acid
Vitamins in Acute Renal Failure
Fat Soluble
• Vit D Def
• Vit A Excess
• Vit E Def
Hypocalcemia
i renal catabolism of
retinol binding protein
i >50% plasma and RBC
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*