1. Pediatric CRRT: Dialysis and Replacement Solutions William E. Smoyer, M.D. Pediatric Nephrology University of Michigan

2. Introduction Variety of CRRT solutions in use Few commercial options for CRRT fluid in some countries (i.e. USA) Major determinants ä Base composition ä Location of preparation ä Timing of preparation

3. Base Composition of CRRT Fluid Replacement Fluid / Dialysate ä Should be nearly physiologic (two exceptions) 1) Cannot combine physiologic Ca ++ and PO 4 -3 2) Need supraphysiologic HCO 3 - Types of Solutions ä Bicarbonate-based solutions (custom made) ä Lactate-based solutions (pre-made)

4. Bicarbonate-Based CRRT Fluid Generally preferred over lactate-based solutions ä Can be used for replacement fluid or dialysate ä Avoids need for conversion of lactate into bicarbonate ä Not stable for long periods due to CO 2 diffusion ä More expensive than lactate-based solutions ä Not widely commercially available No marketed solutions in USA Marketed as “Hemosol” in Canada and Europe

5. Bicarbonate-Based CRRT Fluid Phosphorus-based Solution ä Requires continuous calcium infusion CaCl 2 titrated to keep Ca ++ at 1-1.3 mEq/L Calcium-based Solution ä Requires continuous phosphorus infusion Na 3 PO 4 at 1-2 mmol/kg/d

6. Bicarbonate-Based CRRT Fluid Options for Therapy ä Custom made in hospital pharmacy (most common) ä Generated by hemodialysis machine 1 ä Alternating Ca- and HCO 3 -based solutions (hourly) 0.45% saline + 70 mEq/L NaHCO 3 + 0-4 mEq/L KCl 0.9% saline + 300 mg/L CaCl 2 +200 mg/L MgSO 4 + 0-4 mEq/L KCl ä “Four Bag” Method 2 ä COMPASS Program 1 LeBlanc et al. Am J Kid Dis. 26:910, 1995 2 Mault et al. ASAIO J 30:203, 1984

7. Replacement Fluid or Dialysate Bicarbonate-Based Solutions

8. Lactate-Based CRRT Fluid Stable for long periods Commercially available ä 1.5% peritoneal dialysate ä Lactated Ringer’s solution ä Baxter Premix Dialysate (only FDA-approved) Less expensive than bicarbonate-based fluid Generally used only for dialysate

9. Lactate-Based CRRT Fluid 1.5% Peritoneal Dialysate (Not approved) ä Advantages Pre-made  Can be obtained more quickly Inexpensive ä Disadvantages Lactate may  acidosis (liver failure, poor perfusion) Dextrose is 1500 mg/dL and may  hyperglycemia Na is 132 mEq/L and may  hyponatremia K is 0 mEq/L and may  hypokalemia PO 4 is 0 mEq/L and may  hypophosphatemia

10. Lactate-Based CRRT Fluid Lactated Ringer’s Solution (Not approved) ä Advantages Pre-made  Can be obtained more quickly Inexpensive ä Disadvantages Lactate may  acidosis (liver failure, poor perfusion) Dextrose is 0 mg/dL and may  hypoglycemia Na is 130 mEq/L and may  hyponatremia K is 4 mEq/L (? not desirable if treating hyperkalemia) PO 4 is 0 mEq/L and may  hypophosphatemia

11. Lactate-Based CRRT Fluid Baxter Premix Dialysate (Not for infusion) ä Advantages Pre-made  Can be obtained more quickly Inexpensive ä Disadvantages Lactate may  acidosis (liver failure, poor perfusion) K is 2 mEq/L and may  hypokalemia PO 4 is 0 mEq/L and may  hypophosphatemia

12. Dialysate 1.5% PDLRBaxter Glucose (mg/dL) 1500 0 100 Na (mEq/L) 132130 140 K (mEq/L) 0 4 2 Cl (mEq/L) 96109 117 Ca (mEq/L) 3.5 3 3.5 Phos (mg/dL) 0 0 0 Mg (mg/dL) 0.5 0 1.5 Lactate (mEq/L) 40 28 30 Osmolality (mOsm/L) 346273 297

13. Location of CRRT Fluid Preparation Prepared in hospital (custom made) ä NaHCO 3 -based fluid Prepared in dialysis unit ä NaHCO 3 -based fluid (Hemodialysis machine) 1 Prepared in ICU ä NaHCO 3 -based fluid (“Four Bag” Method) 2 Prepared commercially ä Lactate-based fluid ä NaHCO 3 -based (COMPASS) 1 LeBlanc et al. Am J Kid Dis. 26:910, 1995 2 Mault et al. ASAIO J 30:203, 1984

14. Timing of CRRT Fluid Preparation Stock Solutions ä Generally lactate-based ä Less expensive ä Hospal “Hemosol”(In Canada and Europe) Immediate Use Solutions ä All NaHCO 3 -based ä More expensive

15. CRRT Fluids in Pediatric Programs Both HCO 3 - and lactate-based solutions being used in USA Most programs using HCO 3 -based solutions Most programs using solutions made in hospital pharmacy Few programs using Baxter Premix Dialysate No programs using dialysate generated with hemodialysis machine

16. Summary Variety of CRRT dialysate and replacement solutions available NaHCO 3 -based solutions generally preferable Lactate-based solutions less expensive and more readily available (usually dialysate only) Custom-made solutions have risk of preparation errors Need increased availability of standardized, pre- made NaHCO 3 -based solutions (esp. in USA)