1. Dialysis and Replacement Solutions for CRRT
Jordan M. Symons, MD
University of Washington School of Medicine
Children’s Hospital & Regional Medical Center
Seattle, WA

2. CRRT Solutions: Outline of the Talk
Purpose of solutions in CRRT
Goals for a CRRT solution
Description of solutions currently available for CRRT
Considerations in choosing a solution for CRRT

3. First CAVH Circuit
Kramer, P, et al. Arteriovenous haemofiltration: A new and simple method for treatment of over-hydrated patients resistant to diuretics. Klin Wochenschr 55:1121-2, 1977.

4. CRRT Machines: Current Generation

5. Convective Clearance
To increase clearance by convection, increase ultrafiltration rate (will require more replacement fluids)

6. D
Diffusive Clearance
To increase clearance by diffusion, increase dialysate flow rate

7. Characteristics of the Ideal CRRT Solution
Physiological
Reliable
Inexpensive
Easy to prepare
Simple to store
Quick to the bedside
Widely available
Fully compatible

8. Base in CRRT Solutions Hemodialysis: first acetate, then bicarbonate
Peritoneal dialysis: lactate in North America; bicarbonate in Europe
CRRT: lactate or bicarbonate?

9. Bicarbonate vs. Lactate in CRRT
Both can be used for base
Bicarbonate superior to acetate in HD
PD uses lactate due to technical issues
Is bicarbonate preferable to lactate?

10. Bicarbonate vs. Lactate in CRRT: Blood Lactate Levels
Group 1 (Lactate first)
Group 2 (Bicarb first)
Baseline
Bicarbonate
Lactate
0 – 48 hours
Receiving Lactate
Receiving Bicarb
48 – 96 hours
Zimmerman et al, Neph, Dial & Transpl :

11. Bicarbonate vs. Lactate in CRRT: Blood Lactate Levels in Children
Maxvold et al, Blood Purif 17:#27, 1999 [abstract]

12. Bicarbonate vs. Lactate in CRRT: Cardiovascular Events
Barenbrock M et al, Kid Int 58: , 2000

13. Options for CRRT Solutions
Peritoneal dialysate
Adapted pre-made solutions
Saline, Lactated Ringers
Multi-bag systems
Custom-made solutions
Local pharmacy; outsource
On-line dialysate
Commercially available CRRT solutions

14. Baxter Hemofiltration Solution
Lactate buffered
5 liter bag
Small amount of potassium
Contains calcium

15. Chemical Content of Baxter Hemofiltration Solution
Concentration (mEq/L)
Sodium
140
Calcium
3.5
Magnesium
1.5
Potassium 2
Chloride
117
Lactate 30
Glucose (mg/dL)
100

16. Hemosol (Hospal) 5 liter bag
“L” series (lactate) with variable K+, glucose
“B0” (bicarbonate) needs to be mixed
Not available in US

17. Chemical Content of Hemosol
Ion (mmol/L)
L0, LG2, LG4 B0
Sodium
140 – 142
140
Calcium
1.75
Magnesium
0.75
0.5
Potassium
0 / 2 / 4
Chloride
105 – 109.5
109.5
Lactate 40 3
Bicarbonate 32
Glucose
+/-

18. Normocarb (DSI) Bicarbonate buffered Concentrate must be compounded
Final volume 3.24 liters (240ml concentrate added to 3 L bag)

19. Chemical Content of Normocarb
Ion
Concentration After Mixing (mEq/L)
Sodium
140
Calcium
Magnesium
1.5
Potassium
Chloride
107
Bicarbonate 35

20. PrismaSate (Gambro) Bicarbonate buffered Small amount of lactate
5 liter bag
2 compartments to prevent precipitation
Two ionic formulations

21. Chemical Content of PrismaSate
Ion (mEq/L)
BK0/3.5
BGK2/0
Sodium
140
Calcium
3.5
Magnesium 1
Potassium 2
Chloride
109.5
108
Lactate 3
Bicarbonate 32
Glucose (mg/dL)
110

22. Choosing a Solution: Issues to Consider
Anticoagulation
Cost
CRRT modality
Diffusion (CVVHD)
Convection (CVVH)
Both (CVVHDF)
Patient safety

23. Anticoagulation and Solutions
Calcium?
Baxter Hemofiltration Solution
Yes
Hemosol
Normocarb No
PrismaSate
BK0/3.5 – Yes
BGK2/0 – No
Pharmacy Custom Made
User Choice
May need to consider Ca++ content if using citrate for anticoagulation

24. CRRT Solutions: Costs Base Cost/bag ($US) Preparation Time
Industry Standard
Normocarb
Bicarbonate
27.06
5 min
Yes
Baxter Hemofiltration Solution
Lactate
30.45
3 min
Pharmacy Custom Made
User choice
29.38
45 min No
Bunchman et al, Blood Purif 20: 2002 [abstract]

25. Modality May Have an Impact on Choice of Solutions
Diffusion requires the use of a dialysate
Convection requires the use of replacement fluids R R D

26. What’s the Difference Between Dialysate and Replacement Fluid?
Dialysate is a Device
Replacement Fluid is a Drug

27. FDA Approval Status of CRRT Solutions
Approved as Dialysate?
Approved as Replacement?
Baxter Hemofiltration Solution
Yes No
Hemosol
Yes in Europe/ No in the US
PrismaSate
Pharmacy Custom Made ?
Normocarb
No*

28. Normocarb as Replacement Fluid
FDA Modernization Act of 1997:
“The Act creates a special exemption to ensure continued availability of compounded drug products prepared by pharmacists to provide patients with individualized therapies not available commercially”.
Bunchman et al, AJKD 42(6): , 2000

29. Evaluation of Errors in Preparation of CRRT Solutions
Survey of 3 Pediatric Listserves:
Pediatric Critical Care
Pediatric Nephrology
Pediatric CRRT
31 programs responded to query
Bunchman et al, Blood Purif 22: 2004 [abstract]

30. Prevalence and Consequences of Errors in Solution Preparation
16/31 programs reported errors:
7 errors in replacement solutions
9 errors in dialysate solutions
Consequences of improper solutions
2 deaths
1 non lethal cardiac arrest
6 seizures (hypo/hypernatremia)
7 without complications
Bunchman et al, Blood Purif 22: 2004 [abstract]

31. Policy Changes Resulting from Errors in Solutions
Changed to Normocarb for either replacement or dialysate (11)
Changed to PrismaSate for dialysate (2)
Purchased TPN mixer for solutions (2)
Chemistry lab check of every bag (3)
Bag label check by at least 2 staff (10)
Bunchman et al, Blood Purif 22: 2004 [abstract]

32. CRRT Solutions: Summary
Solutions needed to maximize clearance
Bicarbonate seems superior to lactate
Pharmacy made solutions give greatest flexibility but have increased risks/costs
Several industry-made solutions; none currently approved for replacement
Still no perfect “solution” for this problem

33. Thanks!