Nutrition in CRRT Do the losses exceed the delivery?

1. Nutrition in CRRTDo the losses exceed the delivery? Timothy E. Bunchman

2. Nutrition in MOSF • What are the needs of the patient due to presence of MOSF? • Protein • Carbohydrate • Lipids • What are the losses of the patient due to the therapy of CRRT?

3. Protein & Amino Acid Metabolism • Clinically seen as • Hyper catabolic • E.g. Rapidly rising BUN • Over time loss of lean body mass

4. Protein & Amino Acid Metabolism • Mechanisms • Increase in muscle catabolism • Decrease in muscle protein synthesis • Increase in hepatic • gluconeogenesis • Ureagenesis • Protein synthesis • Altered AA transport (cellular) • Decrease in renal peptide catabolism

5. Protein & Amino Acid Metabolism • Potential causes • Insulin resistance • Metabolic acidosis • Inflammation • Catabolic hormones • Growth hormone/factor resistance • Substrate deficiencies • Malnutrition prior to illness • Loss on dialysis

6. Carbohydrate metabolism • Clinical findings • hyperglycemia

7. Carbohydrate metabolism • Mechanisms • Insulin resistance • Increase in hepatic gluconeogenesis

8. Carbohydrate metabolism • Potential causes • Stress hormones • Inflammatory mediators with increase in cytokine (e.g. TNF) expression • Metabolic acidosis • Pre-existing hyperparathyroidism

9. Lipid Metabolism • Clinical findings • Hypertriglyceridemia

10. Lipid Metabolism • Mechanisms • Inhibition in lipolysis • Increase in hepatic triglyceride secretion

11. Lipid Metabolism • Potential causes • Unknown inhibitor to lipoprotein lipase • Inflammatory mediators

12. Nutrition in PCRRT • CRRT allows solute clearance • uremic solutes • small molecular sized nutrients (eg oligosaccharides) • amino acids and small peptides • electrolytes

13. Is malnutrition an independent predictor of survival in ARF? • Energy Balance studies • Cumulative energy deficits associated with increase mortality • Bartlett et al, Surgery 1986 • 48% mortality in malnourished • 29% mortality in non malnourished • Fiaccudori et al, J Am Soc Neph 1996

14. Nutritional Factors in ARF • Increase in protein catabolism • underlying and cause of ARF • cytokine effects • uremia • increase in gluconeogenesis and protein degradation • hormonal • Insulin resistance, diminished protein synthesis • metabolic acidosis

15. Nutritional Factors in ARF • Dialysis losses • protein losses in PD • amino acid losses in PCRRT • Diminished nutrient utilization • Inadequate supplementation • failure to measure needs • side effects of nutrition supplementation

16. Dialysis Losses • Peritoneal Dialysis • albumin, protein, immunoglobulin and amino acid losses • Katz et al, J Peds

17. IgG levels in Infants(Katz et al, J Peds 117:258-261, 1990)

18. IgG levels in Infants(Katz et al, J Peds 117:258-261, 1990)

19. Dialysis Losses • CRRT • small peptide and amino acid • Mokrzycki and Kaplan, J Am Soc Neph 1996

20. Protein losses on CRRT • Range of amino acid and protein losses • 7-50 gms/day • Factors effecting AA/protein losses • hemofilter size (surface area) and composition • nature of solute (molecular size) • total ultrafiltration • plasma concentration of amino acids/protein

21. Protein losses on CRRTMokrzycki and Kaplan, J Am Soc Neph 1996 • CVVH and CVVHDF • Polysulfone membranes • (Amicon 20 and Fresenius F-80) • BFR 100-300 mls/min • Dx FR 1000 mls/hr with net u/f/hr 1600 mls • 1.2 - 7.5 gms/day of protein losses

22. Protein losses on CRRTDavies et al, Crit Care Med, 1991 • CAVHD • AN-69 (0.43 m2; PAN membrane) • BFR MAP dependent (80 mls/min) • Dx rate @ 1 l/hr; net u/f/hr 340 mls • AA losses at 1 liter Dx: 9% of total intake • Dx rate @ 2 l/hr; net u/f/hr 340 mls • AA losses at 2 liter Dx:12% of total intake

23. Protein losses on CRRTDavenport et al, Crit Care Med 1989 • CVVH • Polyamide FH 55 (Gambro) • BFR 140 mls/min • Net u/f/hr 1000 mls • Amino Acid losses/day by diagnosis • Cardiogenic shock- 7.4 gms • Sepsis-3.8 gms

24. Nutritional losses Replacement fluid vs dialysateMaxvold et al, Crit Care Med 2000 Apr;28(4):1161-5 • Prospective crossover study to evaluate nutritional losses of CVVH vs CVVHD • Study design • Fixed blood flow rate-4 mls/kg/min • HF-400 (0.3 m2 polysulfone) • Cross over for 24 hrs each to pre filter replacement or Dx at 2000 mls/hr/1.73 m2

25. Nutritional losses Replacement fluid vs dialysateMaxvold et al, Crit Care Med 2000 Apr;28(4):1161-5 • Indirect calorimetry to measure REE • TPN source of nutrition @ 120% of REE • 70% dextrose • 30% lipids • Insulin to maintain euglycemia when needed • 10% Aminosyn II • 1.5 gms/kg/day of protein

26. Comparison of Total Amino Acid losses: CVVH vs CVVHD(Maxvold et al, Crit Care Med 2000 Apr;28(4):1161-5) NS Amino Acid Losses (g/day/1.73 m2)

27. Nutritional losses Replacement fluid vs dialysateMaxvold et al, Crit Care Med 2000;28(4):1161-5 • Amino acid and protein losses with this prescription represent between 10-12% of total delivered nutritional proteins • Glutamine loss accounted for approximately 20% of total AA loss • Some Amino Acid preparations for TPN are deficient in glutamine

28. 24 Hr Nitrogen Balance: CVVH vs CVVHD(Maxvold et al, Crit Care Med 2000 ;28(4):1161-5 ) NS 24 hr Nitrogen Balance (g/day/1.73 m2)

29. ? Glucose loss in the Dialysate • 90 kg BMT tx pt with MOSF • Begun on CVVD at 2.5 liters of Normocarb • Due to acidosis 2 liters of Normocarb added as a prefilter replacement fluid therefore the child is now on CVVHDF • Normocarb is glucose free • What is the caloric impact of this?

30. ? Calorie deficient due to no glucose in the Dialysate-2 • Ultrafiltrate glucose is measured at 109 mg/dl • 4.5 liters/hr x 24 hrs = 108 liters uf/day • 109 mg/dl = 1090 mg/l = 1.09 gms/l • 1.09 gms/l x 108 liters = 117 gms of glucose lost • 117 gms x 4 cals/gm = 470 cals lost

31. Is this significant? • IVFs are • TPN giving 2500 cals/day • 5 IVFs for meds, drips, etc all in D5 with a total rate of 200 ccs/hr • 200 ccs/hr x 24 hrs = 4800 ccs of D5 • D5 has 5 gms/100ccs or 50 gms/1000 • 50 gms x 4.8 liters = 24 gms • 24 gms x 4 cal = 96 cals (cals not thought of)

32. Intensive Insulin therapy(Van den Berghe et al NEJM 345:1359-67, 2001)

33. Intensive Insulin therapy(Van den Berghe et al NEJM 345:1359-67, 2001)

34. Intensive Insulin therapy(Van den Berghe et al NEJM 345:1359-67, 2001)

35. Intensive Insulin therapy(Van den Berghe et al NEJM 345:1359-67, 2001)

36. Trace elements and Vitamins • Trace elements are poorly cleared due to protein binding • Water soluble vitamins are well cleared and the child is at risk for deficiency

37. Trace elements and Vitamins • Vitamin A may be retained and cause toxicity manifested as hypercalemia • Vitamin K is not cleared but in patients with MOSF on antibiotics will become deficient and will need supplementation • Vitamin D may be depressed if pt had pre existing renal insufficiency • Vitamin E levels are depressed in MOSF but are not cleared

38. So what do we do? • 1. Keep glucose under control • Use insulin freely (yes some of the insulin is cleared ?? How much?) • If using ACD-A citrate the D stands for Dextrose • (I missed that but I was educated by a NICU nurse)

39. So what do we do? • 2. Keep lipids as part of the formulation but be aware that both glucose and lipids effect triglycerides

40. So what do we do? • 3. Protein load as an amino acid needs to be targeted • Local standard is to target to a BUN of 40-60 mg/dl • Some NICU babies on the current M-60 AN-69 membrane of the PRISMA require 7-9 gms/kg/day to reach a target of BUN to 30 mg/dl

41. Urea Levels: HD vs. HFMehta et al, Kid Int, 2001, 60:1154-1163

42. So what do we do? • 4. Use the gut whenever possible • Benefit of immune function of enteral formulas • Decreases risk of TPN line induced sepsis • Bacterial • fungal

43. A Study to do • Serial nitrogen balance, REE, glucose metabolism studies throughout the course of the child’s illness • Impact upon balance of catabolism to anabolism as one increases the protein/AA exposure