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

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Presentation on theme: "Mortality Outcome Predictors G. Van den Berghe Frontiers in Neuroendocrinology 23 (2002) : 370-391."— Presentation transcript:

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

2 Van Den Berghe G, et al. Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med 2001; 345:1359-1367 N = 1548 pts Prospective,randomized,controlled Study Intensive Insulin Therapy [Glu=80-110] Conventional Insulin Therapy [Glu=180- 200] Diet : 20-30 kcal NP /kg/d, 0.13-0.26 g N/kg/d, 20-40% of kcal NP Lipids.

3 Van Den Berghe G, et al. Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med 2001; 345:1359-1367

4 [Van den Berghe G, et al. Crit care 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

5 rGH 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]

6 Hypothalamic Secretagogues for Pituitary 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]

7 Neuroendocrine Axis Modulation in Acute Illness [Acker CG, et al. A trial of thyroxine in ARF. Kidney Int 2000;57:293- 298] Triiodothyronine Suppl (T 3 ) Mortality [Bettendorf M, et al. Lancet 2000 Aug 12; 356(9229):529-34] 40 Postop Cardiac Children, Randomized, Blinded 2mcg/kg T 3 on Day 1, thereafter 1mcg/kg/d Improved Cardiac Index: 20% (T3) vs 10% (Placebo)

8 Future 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

9 Lipid Utilization:Critical Illness Fatty Acids Oxidation Fat Accrual (Acute) (Prolonged) Leptin

10 NEA : Leptin NEA : Leptin Source –Adipocyte, pulsatile release 16 -kDa Protein hormone, encoded obgene Actions: Appetite Control (Neuropeptide Y) Substrate (Fat) Utilization Bone Metabolism

11 Pediatric 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

12 Nutrition 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

13 Nutrition in ARF Protein Support in Acute Renal Failure: Additive Losses by RRT Nitrogen Balance – Can it Occur in ARF? Special AA formulations?? Additional Cellular Agonists/Antagonists of Muscle Protein turnover

14 Critical 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

15 Nutrition in Pediatric ARF Nutrition 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

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

17 Estimation of Energy Needs Estimation 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) )

18 Energy Requirements in Illness Stress Factors Relative Contribution on Hypermetabolic Needs: Burns 1.2 –2.0 x BEE Neoplasm 1.1-1.3 x BEE Multiple Trauma 1.2-1.4 x BEE Severe Infection/Sepsis 1.2-1.4 x BEE

19 Measurement 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 (Vt i ~Vt e )

20 RQ Measurements Respiratory Quotient (R) : VCO2/VO2 Substrate R Carbohydrate 1.0 Protein 0.8 Fat 0.7 Synthesis of fat >1.0


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