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: Inflammatory Cytokines; Gene Expression Modulation
NeuroEndocrine Axis Phases
Altered Substrate Utilization
Metabolic Alterations in ARF
 catabolism from uremia, acidosis, impaired fluid/solute K
AA Profile / Interconversion in ARF
Vitamin Derangements
Impaired Lipolysis:  Lipase Activity;  LDL & VLDL,  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 [80- • Insulin Dose

110 mg/dl]
• Preventive Effect on
Crit Illness
Polyneuropathy ARF
 Bactermia • Reduction of Mortality
 Inflammation • Prolonged
 Anemia Inflammation
Reduction of Mortality
 CHO Metabolism in Critical
Illness

• Glycolysis:
Glucose>>> 2 Lactate
G°´= - 47.0 kcal/mol
TCA Complete Oxidation:
Glucose + 6 O2 6 CO2 + 6 H2O
G°´= - 686.0 kcal/mol
 Metabolic Alterations in Critical
Illness
• Lipid Utilization in Acute Illness:
Stress Hormones (Catecholamines/Cortisol)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 : • Stress/Acute Phase:
• Albumin, • Fibrinogen
antithrombin, • Ferritin,
• protein C • alpha-1antitrypsinogen
• High Density • anitiproteases
Lipoproteins
 Altered Cellular Metabolism

• Diminished Mitochondrial Energy

Production:
I. Dysfunctional Respiration: Downregulation of
genes coding for electron transport chain
II. Dysfunctional Glycolytic pathway:
Downregulation of gene for PFK (rate limiting
enzyme)
[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) 0.26 MJ/kg/d

>20%
• 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 ~ 185-
290mg/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 : 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
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)
 Glutamine Metabolism
Glutamine Release: • Glutamine Uptake:
 Muscle Free pool Gln • Gut [Supply Dependent]
 Muscle protein • Liver, Spleen, Immune
catabolism System [Active,
 Muscle synthesis of Independent]
Gln
 Glutamine Metabolism
• Rested State: • Catabolic State:
• Rapid Fall in Gln [pl]
• Gln [pl] ~500-600 • >30- 50% Muscle Gln
micromol/L Loss
• Gln [Ms] ~15-20 • Reduced Muscle
Resting Membrane
mmol/L 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 -4.2g/d
 Clinical infections: 3/24 vs 9/21
 Hospital stay: 29 days vs 36 days
[ Schloerb et al; JPEN 1993; 17:407-413]
 Hospital stay: 26 days vs 32 days
 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

 Hypertriglyceridemia in Type II Diabetics.
[Baez-Saldana et al. Am J Clin Nutr 2004;78:238-43]

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
• Heyman SN, etal. Kidney Int 1991;40:273-9
• Gly, Ala Tubular protectant [ischemic or
• nephrotoxic injury]
• Wakabayashi Y, et al. Am J Physiol 1996;270:F784-9
• Arg Preserves renal perfusion
• Singer P, et al. Clin Nutr 1990;9(S):23A
• Badalamenti S, et al. Hepatology 1990;11:379-386
AA Supplementation-  renal perfusion and GFR and
diuresis
 Lipid Metabolism in ARF

•  LDL and VLDL

• Cholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity ~50%
 Lipoprotein Lipase
 Hepatic Triglyceride Lipase
 Cholesterol: Conditional
Essential Nutrient in ARF?
• [Druml et al, Wien Klin Worchenschr 2003;115/21-22:767-
774]
Suppl free Cholesterol [4 g/l] added to 20% Lipid
emulsions
Results:
Reduced Plasma Triglycerides with reduced plasma ½ life
and  total body clearance
Fraction of Lipid Oxidation Improved
 Vitamins in Acute Renal Failure
Water Soluble
• Vit B1 Def Altered Energy Metabolism,
 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
 Vitamins in Acute Renal Failure

Fat Soluble

• Vit D Def Hypocalcemia

• Vit A Excess  renal catabolism of
retinol binding protein
• Vit E Def  >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*