Dialysis and Replacement Solutions for CRRT

Jordan M. Symons, MD

University of Washington School of Medicine

Children’s Hospital & Regional Medical Center

Seattle, WAjordan.symons@seattlechildrens.org

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

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.

First CAVH Circuit

CRRT Machines: Current Generation

Convective Clearance

To increase clearance by convection, increase ultrafiltration rate (will require more replacement fluids)

D

Diffusive Clearance

To increase clearance by diffusion, increase dialysate flow rate

Characteristics of the Ideal CRRT Solution

• Physiological• Reliable• Inexpensive• Easy to prepare• Simple to store• Quick to the bedside• Widely available• Fully compatible

Base in CRRT Solutions

• Hemodialysis: first acetate, then bicarbonate

• Peritoneal dialysis: lactate in North America; bicarbonate in Europe

• CRRT: lactate or bicarbonate?

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?

Zimmerman et al, Neph, Dial & Transpl 1999 14:2387-2391

Bicarbonate vs. Lactate in CRRT:Blood Lactate Levels

Group 1 (Lactate first)

Group 2 (Bicarb first)

Baseline

Bicarbonate

Lactate

16.3 + 1.5

2.4 + 0.8

18.9 + 2.0

1.4 + 0.2

0 – 48 hours

Bicarbonate

Lactate

Receiving Lactate

22.2 + 1.4

2.6 + 0.4

Receiving Bicarb

22.2 + 1.1

1.5 + 0.1

48 – 96 hours

Bicarbonate

Lactate

Receiving Bicarb

24.2 + 2.3

1.8 + 0.6

Receiving Lactate

24.8 + 0.6

3.1 + 0.7

Bicarbonate vs. Lactate in CRRT:Blood Lactate Levels in Children

0

0.5

1

1.5

2

2.5

3

3.5

4

Baseline 8 hrs 16 hrs 24 hrs

Lac

tate

Lev

el

HCO3 soln LR soln

Maxvold et al, Blood Purif 17:#27, 1999 [abstract]

Bicarbonate vs. Lactate in CRRT: Cardiovascular Events

Bicarbonate Lactate

Barenbrock M et al, Kid Int 58:1751-1757, 2000

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

Baxter Hemofiltration Solution

• Lactate buffered

• 5 liter bag

• Small amount of potassium

• Contains calcium

Chemical Content of Baxter Hemofiltration Solution

Ion Concentration (mEq/L)

Sodium 140

Calcium 3.5

Magnesium 1.5

Potassium 2

Chloride 117

Lactate 30

Glucose (mg/dL) 100

Hemosol (Hospal)

• 5 liter bag

• “L” series (lactate) with variable K+, glucose

• “B0” (bicarbonate) needs to be mixed

• Not available in US

Chemical Content of Hemosol

Ion (mmol/L) L0, LG2, LG4 B0

Sodium 140 – 142 140

Calcium 1.75 1.75

Magnesium 0.75 0.5

Potassium 0 / 2 / 4 0

Chloride 105 – 109.5 109.5

Lactate 40 3

Bicarbonate 0 32

Glucose +/- 0

Normocarb (DSI)

• Bicarbonate buffered

• Concentrate must be compounded

• Final volume 3.24 liters (240ml concentrate added to 3 L bag)

Chemical Content of Normocarb

IonConcentration After

Mixing (mEq/L)

Sodium 140

Calcium 0

Magnesium 1.5

Potassium 0

Chloride 107

Bicarbonate 35

PrismaSate (Gambro)

• Bicarbonate buffered

• Small amount of lactate

• 5 liter bag

• 2 compartments to prevent precipitation

• Two ionic formulations

Chemical Content of PrismaSate

Ion (mEq/L) BK0/3.5 BGK2/0

Sodium 140 140

Calcium 3.5 0

Magnesium 1 1

Potassium 0 2

Chloride 109.5 108

Lactate 3 3

Bicarbonate 32 32

Glucose (mg/dL) 0 110

Choosing a Solution: Issues to Consider

• Anticoagulation

• Cost

• CRRT modality– Diffusion (CVVHD)– Convection (CVVH)– Both (CVVHDF)

• Patient safety

Anticoagulation and Solutions

Solution Calcium?

Baxter Hemofiltration Solution

Yes

Hemosol Yes

Normocarb No

PrismaSateBK0/3.5 – Yes

BGK2/0 – No

Pharmacy Custom Made

User Choice

May need to consider Ca++ content if using citrate for anticoagulation

CRRT Solutions: Costs

BaseCost/bag

($US)Preparation

TimeIndustry Standard

Normocarb Bicarbonate 27.06 5 min Yes

Baxter Hemofiltration Solution

Lactate 30.45 3 min Yes

Pharmacy Custom Made

User choice 29.38 45 min No

Bunchman et al, Blood Purif 20: 2002 [abstract]

Modality May Have an Impact on Choice of Solutions

• Diffusion requires the use of a dialysate

• Convection requires the use of replacement fluids

D

R

R

What’s the Difference BetweenDialysate and Replacement Fluid?

Dialysate is a Device

Replacement Fluid is a Drug

FDA Approval Status of CRRT Solutions

SolutionApproved as Dialysate?

Approved as Replacement?

Baxter Hemofiltration Solution

Yes No

HemosolYes in Europe/ No in the US

Yes in Europe/ No in the US

PrismaSate Yes No

Pharmacy Custom Made

? ?

Normocarb Yes No*

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):1248-52, 2000

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]

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]

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]

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

Thanks!