Mortality Outcome Predictors G. Van den Berghe Frontiers in Neuroendocrinology 23 (2002) : 370-391.

Mortality Outcome PredictorsMortality Outcome PredictorsG. Van den BergheG. Van den Berghe Frontiers in NeuroendocrinologyFrontiers in Neuroendocrinology

23 (2002) : 370-39123 (2002) : 370-391

Van Den Berghe G, et al. Intensive Insulin Van Den Berghe G, et al. Intensive Insulin Therapy in Critically Ill Patients. Therapy in Critically Ill Patients. N Engl J Med N Engl J Med

2001; 345:1359-13672001; 345:1359-1367

N = 1548 ptsProspective,randomized,controlled StudyIntensive Insulin Therapy [Glu=80-110]Conventional Insulin Therapy [Glu=180-

200]

Diet : 20-30 kcalNP/kg/d, 0.13-0.26 g N/kg/d,

20-40% of kcalNP Lipids.

Van Den Berghe G, et al. Intensive Insulin Van Den Berghe G, et al. Intensive Insulin Therapy in Critically Ill Patients. Therapy in Critically Ill Patients. N Engl J Med N Engl J Med

2001; 345:1359-13672001; 345:1359-1367

[Van den Berghe G, et al. Crit care [Van den Berghe G, et al. Crit care Med 2003; 31:359-366]Med 2003; 31:359-366]

Glycemic Control: [80-110 mg/dl]

Crit Illness Polyneuropathy Bactermia Inflammation Anemia Reduction of Mortality

Insulin Dose: Preventive Effect on

ARF Reduction of Mortality Inflammation

rGH Therapy in Critical IllnessrGH Therapy in Critical Illness

Finnish ( N=170) and MultiNational (N=190)

Enrolled > 5 ICU days; rGH = 5.3/8.0 mg/d

Hyperglycemia and Insulin Suppl

Sepsis and MOF,

Improved Nitrogen Balance (Finnish)

rGH Supplementation Mortality RR= 2.4[Takala J, et al. Increased Mortality associated with Growth Hormone Treatment

in Critically Ill Patients. N Engl J Med 1999;341:785-92]

Hypothalamic Secretagogues for Hypothalamic Secretagogues for Pituitary and Metabolic ImprovementPituitary and Metabolic Improvement

N=14, Prolonged Illness> 14 ICU days

GHRP-2 + TRH for 5 day therapy crossing over to placebo

6:00 am GHRP-2 bolus 1 mcg/kg and TRH bolus of 1 mcg/kg, then

continuous infusion of 1mcg/kg/hr

Restored the pulsatile profile of GH and TSH and + peripheral responses (IGF-I, IGFBP-3, ALS,Leptin, Insulin)

No effect of Cortisol levels Improved Urea to creatinine ratio [Van den Berghe G, et al. J Clin Endocrinol Metab 84: 1311-1323, 1999]

Neuroendocrine Axis Modulation in Neuroendocrine Axis Modulation in Acute IllnessAcute Illness

[Acker CG, et al. A trial of thyroxine in ARF. Kidney Int 2000;57:293-298]

Triiodothyronine Suppl (T3)Mortality

[Bettendorf M, et al. Lancet 2000 Aug 12; 356(9229):529-34]

40 Postop Cardiac Children , Randomized, Blinded

2mcg/kg T3 on Day 1, thereafter 1mcg/kg/dImproved Cardiac Index: 20% (T3) vs 10% (Placebo)

Future Nutritional AdaptionsFuture Nutritional Adaptions

Potential Endocrine Intervention in ARF: Ding H, et al. J Clin Invest 1993; 91:2281-7

IGF-1 Accelerate Regeneration in ARF,

Improved Nitrogen Balance Hirschberg R, et al. Kidney Int 1999; 55:2423-32

IGF-1 No clinical effect in ARF patients

Lipid Utilization:Critical IllnessLipid Utilization:Critical Illness

Fatty Acids

Oxidation Fat Accrual(Acute) (Prolonged) Leptin

NEA : LeptinNEA : Leptin

Source –Adipocyte, pulsatile release 16 -kDa Protein hormone, encoded “ob”gene

Actions: Appetite Control (Neuropeptide Y) Substrate (Fat) Utilization Bone Metabolism

Pediatric NutritionPediatric Nutrition

Components of Pediatric Nutrition in ARF:

1. Growth and Development of Child

2. Cessation anabolic growth during acute

illness:

A.Maintenance of Cellular Metabolism

B. Repair / Healing Process

Nutrition in ARFNutrition in ARF

Acute Renal Failure Nutritional Effects:

1. High Protein Catabolic Rate

2. Altered Amino Acid Profile

3. Altered Substrate Utilization and Elimination

4. Altered Renal Solute Clearance and UF

5. Altered Renal Synthetic Function

Nutrition in ARFNutrition in ARF

Protein Support in Acute Renal Failure:Additive Losses by RRTNitrogen Balance – Can it Occur in ARF?Special AA formulations??Additional Cellular Agonists/Antagonists of

Muscle Protein turnover

Critical Care NutritionCritical Care Nutrition

Nutritional Components of Critical Illness:

1. Daily Energy Needs/Expenditure

2. Energy Formulation

3. Substrate Utilization

4. Stage of Critical Illness- Neuroendocrine Axis

5. Euglycemic Control

Nutrition in Pediatric ARFNutrition in Pediatric ARF

Age ( ~m2) BMR*(kcal/m2/hr) REE (kcal/d) 0-1 (.34-.45) 53 320-500 2-6 (.58-.8) 52-47 740-950 7-10 (1.0) 47-42 1130 11-14(m/1.4) 43-42 1440 11-14(f/1.4) 42-39 1310 15-18(m/1.7) 41-40 1760 15-18(f/1.6) 37-35 1370 BMR* from Fleisch table of basal met standards

Developmental/Age Effect on Energy Developmental/Age Effect on Energy and Protein Needs (RDA)and Protein Needs (RDA)

Age Wt BMR REE RDA Protein N:Calorie

Infant 9 53 500 972 2 1:337

Child 30 43 1130 2400 1.2 1:416

Adoles 70 40 1760 2700 0.8 1:301

Healthy: Nitrogen to Calories ~ 1:350

Critical Illness: Nitrogen to Calories ~ 1:150

Estimation of Energy NeedsEstimation of Energy Needs

Harris Benedict Equation:Males BEE = 66 + (13.7 x W(kg)) + (5 x

H(cm)) – (6.8 x A (yr))

Females BEE= 655 + (9.6 x W(kg)) + (1.7 x

H(cm)) – (4.7 x A (yr))

Energy Requirements in Energy Requirements in IllnessIllness

Stress Factors Relative Contribution on Hypermetabolic Needs:

Burns 1.2 –2.0 x BEENeoplasm 1.1-1.3 x BEEMultiple Trauma 1.2-1.4 x BEESevere Infection/Sepsis 1.2-1.4 x BEE

Measurement of REEMeasurement of REE

Indirect Calorimetry

REE (kcal/d) = VO2 (L/min) x 4.3(kcal/L)

+ VCO2 (L/min) x 1.1 (kcal/L) x 1440

Steady state of activity, FiO2 ~60% or less,

minimal leak (Vti ~Vte)

RQ MeasurementsRQ Measurements

Respiratory Quotient (R) : VCO2/VO2

Substrate RCarbohydrate 1.0Protein 0.8Fat 0.7Synthesis of fat >1.0