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What’s New in Nutrition?. NJ Maxvold MD Associate Professor of Pediatrics Pediatric Critical Care Medicine DeVos Children’s Hospital. Nutrition and PCRRT. Is there anything New? Current General Knowledge: Stress Response elicits change in Utilization of Fuel/Substrates: - PowerPoint PPT Presentation
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What’s New in Nutrition?
NJ Maxvold MD
Associate Professor of Pediatrics
Pediatric Critical Care Medicine
DeVos Children’s Hospital
Nutrition and PCRRT
Is there anything New?
Current General Knowledge:
Stress Response elicits change in Utilization of Fuel/Substrates:
1. Cellular (End Organ) Insulin Resistance, therefore hyperglycemia and altered cellular energetics
2. Fatty Acids increased utilization as Glucose Utilization becomes Inefficient
3. Protein metabolism shift from anabolism to catabolism
4. Phasic changes in metabolism during acute Illness
Nutrition and PCRRT
Carbohydrate Utilization• Limit of oxidation of Carbohydrate
~ 5 mg/kg/min of Glucose
• Hyperglycemia Insulin Resistance
Gluconeogenesis
Nutrition and PCRRT
Lipid Metabolism Fatty Acid Utilization (major myocardial oxidation fuel)
Mitochondrial adaptation to acute stress (Carnitine dependent enzymes) Calvani et al Basic Res Cardiol 2000Mitochondrial control of FFA oxidation and CHO oxidation AcetylCoA/ CoA ratio on PDH Complex
Nutrition and PCRRT
High Protein Catabolism• Muscle Efflux of Amino Acids to fuel
Gluconeogenesis
• Protein metabolism shift from anabolic to Acute phase proteins
(Hepatic Inflammatory Response)
Net Negative Nitrogen Balance
Critical Illness
hormone changes-Acute: increase-Later: decrease
↑ cytokines Altered substrate utilizationCHO: ↑hepatic gluconeogenesis (shift away from liver glycolysis)Hyperglycemia- Inefficient glucose oxidation- Insulin resistance- Shift in use of amino acids: gluconeogenesis + APR’s
MALNUTRITION
Acute Kidney Injury
UremiaAcidosisAltered Glucose metab.
Cytokines
Impaired nutrient transportInefficient/inadequate supplyImpaired A.a. conversion↓lipid oxidation
Nutrition and PCRRT
Impaired Nutrient Support: Diminished Cellular Energy
• Inefficiency of normal cellular transport activities:
• Disturbances in the Na/K ATPase pump (energy dependent function)
• Intracellular mitochondrial adaptations (Dysfunctional electron transport respiration)
Muscle wasting & Malnutrition Mortality
Nutrition and PCRRT Adequate Calories: REE or Indirect Calorimetry ??Should we add 10-15 % or More??
REE in Children : 35-60 kcal/kg/d Briassoulis et al Crit Care Med 2000
MEE in Crit Ill Children: 30-35 kcal/kg/d ?? How soon?? Heyland D et al JPEN 2003 24-48 Hrs
Indirect calorimetry AND CRRT
• IC: measure resting energy expenditure.• Based on: Expired CO2 and O2 (O2 consumption +
CO2 production).
Potential problem with CRRT
Hemofilter
Dialysis fluidEffluent
HCO3/CO2 fluxes May affect ICmeasurements.
IC may not be reliable?
Nutrition and PCRRT
• Protein Support for Nitrogen Balance:
• Nitrogen Intake = Nitrogen Output
Protein Catabolic Rate in AKI: Macias et al JPEN 1996
~ 1.4 -1.7 g/kg/day
Maxvold et al Crit Care Med 2000
~ 1.2 - 1.8 g/kg/day
Nutrition and PCRRT
Can Nitrogen Balance be Achieved in AKI patients on CRRT? Conflicting Studies Bellomo et al Ren Fail 1997
Protein Intake : Nitrogen Balance 1.2 g/kg/d AA -5.5 g N /d 2.5 g/kg/d AA -1.9 g N /d
Does Increasing Protein Intake Help?
Scheinkestel et al Nutrition 2003
• 11 critically ill adults on CRRT, protein intake 2.5 g/kg/day a) normal amino acid levels b) positive nitrogen balance.
• 50 critically ill adults on CRRT: 1.5 vs 2.0 vs 2.5 g/kg/day. NB related to protein intake. NB related to hospital stay Protein intake 2.5 g/kg/d: improved survival!
Protein and calorie prescription for children and young adults receiving CRRT: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry group. Zappitelli et al, submitted.
0
1
2
3
4
5
1 2 3 4 5 6 7 8 9 10excludes outside values
Protein intake(g/kg/day)
Day of CRRT
Daily change in protein prescription during treatment with CRRT.
Protein and calorie prescription for children and young adults receiving CRRT: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry group. Zappitelli et al, submitted.
Characteristics (N) Protein intake (g/kg/day) Initial Maximal
Gender Males (111) Females (84) p-value1
Age Group≤ 1 year (35)1 to ≤13 years (95)>13 years (65)p-value
MODS (155)No MODS (40)p-valueSurvival Survivors (117) Non-survivors (78) p-valueCRRT indication Electrolytes (31) Fluid overload (66) Electrolytes and fluid overload (98) p-value
1.4, 1.0[1.4] 2.0, 1.6[1.6]1.3, 1.0[1.2] 1.9, 1.8[1.5] 0.7 0.9
1.5, 1.8[1.5] 2.5, 2.4[2.3] 1.3, 1.0[1.2] 2.0, 1.9[1.5] 1.4, 1.0[1.0] 1.6, 1.3[1.1] 0.09 0.009*
1.3, 1.0[1.2] 1.9, 1.8[1.5]1.5, 1.0[0.8] 2.0, 1.3[1.7] 0.1 0.2
1.4, 1.0[1.2] 2.0, 1.6[1.5]1.3, 1.0[1.3] 1.8, 1.8[1.7] 0.6 0.9
1.2, 1.0[0.9] 1.6, 1.4[1.1]1.6, 1.2[1.2] 2.1, 1.8[1.8]1.2, 1.0[1.3] 2.0, 1.8[1.6] 0.07 0.2
All groups:-Maximal protein>initial
Multivariate predictors ofmaximal protein intake
- Younger age- Higher initial protein Rx- #CRRT days
Protein Rx >2g/kg/day in 40%
Amino acid, trace metal and folate clearance by continuous renal replacement therapy in critically ill children. Zappitelli et al, submitted
CVVHD initiation (N=15) Day 2 (N=15) Day 5 (N=9)Mean±SD, Median Mean±SD, Median Mean±SD, Median
Protein intake (g/kg/d)N balance (g/kg/d)Caloric intake (kcal/kg/d)Caloric balance (kcal/kg/day)
1.98±1.24, 1.75 2.04±1.02, 2.09 1.85±0.60, 2.08
NA -0.88±1.60, -0.22 -0.23±0.19, -0.24
32.6±27.6, 23.8 40.3±22.3, 33.6 43.2±18.4, 42.7
-0.4±25.4, -8.0 +7.7±21.7, +1.5 +10.6±17.7, +10.8
Protein and energy intake and output at CVVHD1 initiation, Day 2 and Day 5.
Maxvold et al, Crit Care Med, 2000
Protein intake was 1.5 g/kg/day – Negative nitrogen balance
It’s not easy to achieve a positive nitrogen balance.
Logic: bigger filter, higher Qd or Quf = increased clearance
Amino acid, trace metal and folate clearance by continuous renal replacement therapy in critically ill children. Zappitelli et al, submitted
Amino Acid
Day 2 (n=15) Day 5 (n=9)K1 CVVHD CVVHD Losses K Renal (n=2) K CVVHD CVVHD Losses K Renal (n=3)(ml/min/1.73m2) (mcg/kg/d) (ml/min/1.73m2) (ml/min/1.73m2) (mcg/kg/d) (ml/min/1.73m2) Mean±SD, Median Mean±SD, Median Mean Mean±SD, Median Mean±SD, Median Mean
TauAspThrSerAsnGluGlnProGlyAlaCitValCysMetIleLeuTyrPheOrnLysHisArg
104.5±179.0, 32.9 8.4±11.1, 4.8 1.0 77.8±111.2, 24.2 4.5±5.4, 1.8 2.1335.8±483.7, 53.6 3.9±4.1, 3.2 2.6 234.0±349.8, 51.1 5.6±4.4, 2.6 12.031.9±25.0, 22.6 15.7±18.5, 9.9 4.1 38.8±25.1, 29.8 11.9±5.9, 12.0 18.929.1±25.6, 17.8 8.1±8.6, 5.7 3.6 34.6±27.7, 22.3 6.0±3.3, 5.0 9.237.2±32.1, 32.3 7.7±8.1, 4.5 9.8 35.5±19.8, 34.3 5.0±3.4, 5.3 28.69.4±10.6, 6.2 2.7±4.0, 1.8 0.6 6.1±5.0, 3.8 1.6±0.7, 1.7 1.019.4±20.1, 13.2 47.4±63.7, 23.0 2.2 85.4±152.9, 21.2 44.2±30.7, 34.5 0.738.3±32.7, 31.2 24.3±22.2, 17.6 0.2 37.5±21.9, 27.3 19.4±11.2, 20.5 0.828.1±25.7, 18.0 16.0±16.1, 7.5 3.9 35.3±30.2, 19.8 12.0±7.1, 14.1 12.926.1±24.6, 15.4 23.4±21.2, 13.5 5.2 37.9±38.8, 25.2 20.0±11.5, 24.1 6.925.6±24.3, 15.9 2.8±4.5, 1.3 4.1 39.3±50.4, 25.7 1.5±1.1, 1.4 5.724.8±22.0, 14.8 16.8±13.4, 12.7 5.2 39.1±37.3, 25.1 14.4±6.9, 13.9 5.527.4±54.5, 8.6 0.8±1.2, 0.5 0.5 34.7±29.9, 44.3 1.3±1.1, 1.1 5.218.0±19.9, 8.2 5.9±13.5, 12.7 3.6 26.8±31.1, 17.2 2.2±1.8, 2.2 5.129.9±29.8, 17.3 6.0±5.7, 4.3 6.9 38.6±34.7, 22.1 5.4±2.7, 4.3 6.622.9±20.9, 13.6 11.6±9.2, 7.8 3.9 32.2±28.8, 22.7 10.3±5.2, 10.9 4.422.2±23.3, 10.7 9.2±13.5, 4.3 4.4 36.5±41.3, 21.4 5.6±2.7, 5.2 10.523.9±20.8, 12.9 18.4±23.1, 7.8 4.5 34.9±29.7, 26.4 11.3±6.2, 10.1 7.08.4±8.7, 12.9 3.4±5.0, 1.0 0.3 91.0±249.7, 10.6 2.5±3.4, 1.4 0.77.7±9.0, 2.8 10.0±11.1, 4.4 0.3 108.4±299.5, 9.6 8.7±8.9, 5.6 0.913.2±15.8, 10.0 8.0±15.9, 2.8 0.7 33.4±66.3, 15.7 4.5±3.8, 5.1 12.115.8±17.1, 8.0 11.4±23.4, 3.5 1.8 45.8±68.6, 8.6 6.0±4.8, 4.1 6.2
CVVHD clearance of amino acids measured on Day 2 and Day 5 N=15
0
10
20
30
40
50
60
K
ml/min/1.73m 2
Thr Glu Gln Pro Gly Ala Val Met Phe Lys His Arg
Amino Acids
Combined results of clearance of essential amino acids by CRRT. Zappitelli et al (submitted) and Maxvold et al, Critical Care, 2000 (n=6).
Several studies, adult and child: ~ 10-20% intake “lost” through hemofilter.
Both studies: Highest losses with Glutamine/Glutamic acid
Critical Illness – trace metals
• Deficiencies linked to:
- Lymphocyte dysfunction
- Cardiovascular dysfunction
- Platelet activity
- Antioxidant function
- Wound healing
Amino acid, trace metal and folate clearance by continuous renal replacement therapy in critically ill children. Zappitelli et al, submitted
K1 Day 2 K Day 5 Serum concentrations _____________________ (ml/min/1.73m2) (ml/min/1.73m2) Initiation Day 2 Day 5 Reference range2
SeleniumCopperChromiumZincManganeseFolate
10.1±7.2, 9.5 8.6±3.9, 7.2 55±19, 49 61±24, 59 64±23, 63 23 to 190 (µg/l) 0.4±0.3, 0.3 0.54±0.46, 0.44 88±21, 87 L3 110±27, 106 104±27, 103 90 to 190 (µg/dl)24.0±10.6, 25.4 24.7±7.1, 26.0 2±1, 2 2±1, 2 2±0.4, 2 0 to 2.1 (µg/l)4.2±4.1, 3.2 4.0±2.4, 2.9 66±44, 53 L 68±28, 61 76±38, 68 60 to 120 (µg/dl)9.0±12.9, 4.6 38.2±121.4, 5.1 9±16, 4 H3 8±15, 3 H 8±15, 3 H 0 to 2 (µg/l)29.4±54.9, 16.2 15.6±3.2, 16.3 16±12, 12 10±4, 9 8±2, 7 5.4 to 40 (ng/l)
Churchwell et al, NDT, 2007
Critically ill adults receiving CVVHD and CVVHDFTransmembrane clearancesMuch lower clearance of selenium and chromiumOverall, trace metal clearance negligible.
CRRT-Vitamins
02468
10121416
Serum folate level (ng/ml)
Pre CRRT Day 2 Day 5
Day of CRRT
Amino acid, trace metal and folate clearance by continuous renal replacement therapy in critically ill children. Zappitelli et al, submitted
**
Nutrition and PCRRT
Berger et al AM J Clin Nutr 2004
24º Balance Studies Intake (Replacement Fluid) = Output (Effluent)
[SeRF] = [SeEff] -0.97 µmol (2 x RI)
[CuRF] = [CuEff] -0.54 µmol (0.3 x RI)
[Vit B1RF] = [Vit B1Eff] -4.12 mg (1.5 x RI)
[ZnRF] = [ZnEff] 20.7 µmol (1.5 x RI) Negative Balance for Se, Cu, VitB1 and Se and VitB1 Losses > 1.5 x the Recommended Intake
Critical Illness - Vitamins
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 acidPotential for losses during CRRT.
Critical Illness - Vitamins
Fat Soluble
• Vit D Def Hypocalcemia
• Vit A Excess renal catabolism of
retinol binding protein
• Vit E Def >50% plasma and
RBC
Critical Illness & AKI - Lipids
LDL and VLDL
• Cholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity ~50%
Lipoprotein Lipase
Hepatic Triglyceride Lipase
Nutrition and PCRRT
Initial Nutritional Prescription for Kids with AKI on CRRT:
• Early Nutrition : 24-48 hrs of PICU admission • Enteral feeding + Parenteral feeding (often require partial Parenteral Nutrition early in acute illness) • REE for age (without additional kcal % allowance) ( REE is already >33% Above mean MEE )
• MEE if available
Initial Nutritional PrescriptionPediatric AKI on CRRT
Component Prescription:
CHO
Fat
Protein
Vitamins
Trace elements
Monitoring
Consider
4-5 mg/kg/min Glucose support [5.8-7.2 g/kg/d] (Insulin as needed for Hyperglycemia)
0.5-1g/kg/d
2 to 3 g/kg/day with AKI (Increase intake if on High flow CRRT (by 20%)
Daily recommended intake (± replacement ) Monitor serum folate, water soluble vitamin levels
Daily Recommended Intake
MEE, Nitrogen Balance, Electrolytes, Vitamins, Trace elements
-Pharmaconutrients: Glutamine, Ala, Se, Omega 3 FA, L-Carnitine, etc
Nutrition and PCRRT
Future Development
PharmacoNutrients:
• Gln
• Omega 3 Fatty Acids
• Arginine
• L-Carnitine
• Growth Factors
PharmacoNutrients
Singer et al Intensive Care Med 2008
• Omega-3 FA: Augment immune defense through inhibition of NF-kappaß
Luiking st al Crit Care Med 2007 Kalil et al Crit Care Med 2006
• Arginine: + Effect - Improved microcircuation, gut function, Plt and WBC Adherence,Endothelial function
- Effect -Hemodynamic Instability, Oxidative Stress
Prevot et al Pediatr Nephrol 2009
• Growth Factors (IGF-1, GH, Insulin)
Glutamine: Conditionally Essential Nutrient
• Substrate for Rapidly dividing cells(Kidney tubular cells, Enterocytes, Immune cells)
• Precursor for Glutathione• Substrate for Gluconeogenesis• Substrate for Ammoniagenesis• Osmotic regulator, • Precursor of purine/pyridimine
Potential Beneficial Effects of Glutamine
Fuel forFuel forEnterocytesEnterocytes
Fuel forFuel forLymphocytesLymphocytes
Nuclotide Nuclotide SynthesisSynthesis
Maintenance ofMaintenance ofIntestinalIntestinalMucosal BarrierMucosal Barrier
Maintenance ofMaintenance ofLymphocyteLymphocyteFunctionFunction
Preservation Preservation of TCA Functionof TCA Function
Decreased FreeRadical availability (Anti-inflammatory action)
GlutathioneGlutathioneSynthesisSynthesis
GLNGLNpoolpool
GlutamineTherapy
Enhanced HeatEnhanced Heat Shock ProteinShock Protein
Anti-cataboliceffect
Preservation of Muscle mass
Reduced Reduced TranslocationTranslocationEnteric BacteriaEnteric Bacteriaor Endotoxinsor Endotoxins
Reduction ofReduction ofInfectious Infectious complicationscomplications
Inflammatory Cytokine Inflammatory Cytokine AttenuationAttenuation
Preserved CellularEnergetics- ATP content
GLNGLNPoolPool
Critical IllnessCritical Illness
Enhanced insulin sensitivity
• CRISIS Trial: Multicenter Pediatric Trial ofEnteral Se, Zn, Gln, IV Metoclopramide
1º Outcome: Time between PICU [DOA] and Infection [nosocomial or clinical]
• REDOXS Study: Multicenter Adult Trial 4 Treatment Arms: Gln; Gln and AntiOxidants; Antioxidants; Placebo Remember!
Gln Loss on CRRT:15-20% of Total AA Clearance
Glutamine Studies
Nutrition and PCRRT
Carnitine Studies
• Conditionally Essential Supplement• Improved Mitochondrial Cellular
Energetics
Nutrition in PCRRT
Carnitine Role in Cell Energetics:• Facilitates Long Chain AcylCoA
[transformed FattyAcids within cytosol]
• Diminishes Acetyl CoA/CoA Ratio -
Improves the PDH Complex Activity• Increases Pyruvate Oxidation and
decreases Lactate Production
Nutrition in PCRRT
That’s Enough for Now!
Many Thanks and Gratitude :Dr. Bunchman Dr. Zappitelli
My Associates in Michigan, especially the PICU nurses!