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

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.

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?

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 Receiving Lactate 22.2 + 1.4 2.6 + 0.4 Receiving Bicarb 22.2 + 1.1 1.5 + 0.1 48 – 96 hours 24.2 + 2.3 1.8 + 0.6 24.8 + 0.6 3.1 + 0.7 Zimmerman et al, Neph, Dial & Transpl 1999 14:2387-2391

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

Bicarbonate vs. Lactate in CRRT: Cardiovascular Events 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 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 Magnesium 0.75 0.5 Potassium 0 / 2 / 4 Chloride 105 – 109.5 109.5 Lactate 40 3 Bicarbonate 32 Glucose +/-

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

Chemical Content of Normocarb Ion Concentration After Mixing (mEq/L) Sodium 140 Calcium Magnesium 1.5 Potassium 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 Calcium 3.5 Magnesium 1 Potassium 2 Chloride 109.5 108 Lactate 3 Bicarbonate 32 Glucose (mg/dL) 110

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

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

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]

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

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

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*

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!