Dialysis and Replacement Solutions for Pediatric 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

CAVH: Good for Fluid Balance,Not So Good for Metabolic Balance

• CAVH removes all molecules slowly– Good for BP stability (slow UF)– Not so good for metabolic control

• Need method to increase molecular clearance without increasing UF rate

Diffusion

• Small molecules diffuse easily

• Larger molecules diffuse slowly

• Dialysate required– Concentration gradient– Faster dialysate flow

increases mass transfer

Convection

• Small/large molecules move equally

• Limit is cut-off size of membrane

• Higher UF rate yields higher convection but risk of hypotension

• May need to Replace excess UF volume

H2O

H2O

H2O

H2O

Neg Press

Solutions in CRRT Address Molecular Control Issues

• Improved mass transfer using diffusion, high-grade convection, or combination– CVVH: a pure convection modality– CVVHD: a diffusion modality– CVVHDF: combined convection/diffusion

• Permits correction of metabolic abnormalities

• Provides “complete” renal replacement

Characteristics of the Ideal CRRT Solution

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

Options for CRRT Solutions

• Peritoneal dialysate:

• Pre-made IV solutions:– Saline, Lactated Ringers

• Multi-bag systems:

• Custom-made solutions:– Local pharmacy; outsource

• Commercially available CRRT solutions

NO

MAYBE

UNNECESSARY

RARELY

Commercial Solutions for CRRT: Several Companies, Multiple Options

• Previously: limited options– No bicarbonate-based solutions– US regulations re: “drug” vs. “device”

• Currently: multiple manufacturers each offering a variety of formulations– Bicarbonate as primary or only base

• The Choice: may depend on local policy, vendors, economic pressures

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

Potassium 0

Chloride 107

Bicarbonate 35

Calcium 0

Magnesium 1.5

Normocarb HF (DSI)

• Bicarbonate buffered

• Concentrate must be compounded

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

• 2 ionic formulations– Normocarb HF 25– Normocarb HF 35

Chemical Content of Normocarb HF

Ion (mEq/L) HF 25 HF 35

Sodium 140 140

Potassium 0 0

Chloride 116.5 106.5

Bicarbonate 25 35

Calcium 0 0

Magnesium 1.5 1.5

PrismaSate (Gambro)

• Bicarbonate buffered

• Small amount of lactate

• 5 liter bag

• 2 compartments to prevent precipitation

• Six ionic formulations

Chemical Content of PrismaSateIon (mEq/L) BK0/3.5 BGK2/0 BGK4/0/1.2 BGK4/2.5 B22GK4/0 BK2/0

Sodium 140 140 140 140 140 140

Potassium 0 2 4 4 4 2

Chloride 109.5 108 110.2 113 120.5 108

Bicarb 32 32 32 32 22 32

Lactate 3 3 3 3 3 3

Calcium 3.5 0 0 2.5 0 0

Magnesium 1 1 1.2 1.5 1.5 1

Gluc(mg/dL) 0 110 110 110 110 0

PrismaSol (Gambro)

• Bicarbonate buffered

• Small amount of lactate

• 5 liter bag

• 2 compartments to prevent precipitation

• Seven ionic formulations

Chemical Content of PrismaSol

Ion (mEq/L)BK

0/3.5BGK 2/0

BGK 2/3.5

BGK 4/2.5

BGK 4/0

BGK 0/2.5

BK 0/0

Sodium 140 140 140 140 140 140 140

Potassium 0 2 2 4 4 0 0

Chloride 109.5 108 111.5 113 110.5 109 106.5

Bicarb 32 32 32 32 32 32 32

Lactate 3 3 3 3 3 3 3

Calcium 3.5 0 3.5 2.5 0 2.5 0

Magnesium 1 1 1 1.5 1.5 1.5 1.5

Gluc(mg/dL) 0 100 100 100 100 100 0

Accusol (Baxter)

• Bicarbonate buffered

• No lactate

• 2.5 liter bag

• 2 compartments to prevent precipitation

• Five ionic formulations

Chemical Content of AccusolIon (mEq/L) 5B9248 5B9249 5B9250 5B9251 5B9252

Sodium 140 140 140 140 140

Potassium 4 2 0 2 2

Chloride 113.5 111.5 109.5 116.3 113.5

Bicarb 35 35 35 30 30

Lactate 0 0 0 0 0

Calcium 3.5 3.5 3.5 2.8 0

Magnesium 1 1 1 1.5 1.5

Gluc (mg/dL) 100 100 0 100 100

Duosol (B.Braun)

• Bicarbonate buffered

• No lactate

• 5 liter bag

• 2 compartments to prevent precipitation

• Three ionic formulations

Chemical Content of DuosolIon (mEq/L) 4450 4451 4452

Sodium 136 140 140

Potassium 2 0 2

Chloride 107 109 111

Bicarb 25 35 35

Lactate 0 0 0

Calcium 0 3 3

Magnesium 1.5 1 1

Gluc (mg/dL) 0 100 100

NxStage PureFlow (NxStage)

• Part of NxStage System One for acute care

• 5 liter bags

• Choice of buffers– Lactate: 3 formulations;

single-chamber bag– Bicarbonate: 5 formulations;

dual-chamber bag

Chemical Content of NxStage PureFlow (1)

Ion (mEq/L)Lactate Buffer

RFP-204 RFP-205 RFP-207

Sodium 140 140 140

Potassium 1 3 1

Chloride 105 112 100

Bicarbonate 0 0 0

Lactate 40 35 45

Calcium 3 3 3

Magnesium 1 1 1

Glucose (mg/dL) 100 100 100

Chemical Content of NxStage PureFlow (2)

Ion (mEq/L)Bicarbonate Buffer

RFP-400 RFP-401 RFP-402 RFP-453 RFP-454

Sodium 140 140 140 130 130

Potassium 2 4 0 2 4

Chloride 111 113 109 108.5 110.5

Bicarbonate 35 35 35 25 25

Lactate 0 0 0 0 0

Calcium 3 3 3 0 0

Magnesium 1 1 1 1.5 1.5

Gluc (mg/dL) 100 100 100 100 100

Choosing a Solution: Issues to Consider

• Cost

• Anticoagulation

• Patient safety

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

Anticoagulation and Solutions

Solution Calcium?

Normocarb HF No

Accusol 4 Yes; 1 No

PrismaSate 2 Yes; 4 No

PrismaSol 4 Yes; 3 No

Duosol 2 Yes; 1 No

NxStage PureFlow 6 Yes; 2 No

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

Evaluation of Errors in Preparation of CRRT Solutions

• Survey of 3 Pediatric Listserves:– Pediatric Critical Care, Nephrology, CRRT

• 16/31 programs reported solution compounding errors

• Consequences of improper solutions– 2 deaths– 1 non lethal cardiac arrest– 6 seizures (hypo/hypernatremia)– 7 without complications

Barletta et al, Pediatr Nephrol. 21(6):842-5, 2006 Jun

FDA Approval Status of CRRT Solutions

Solution FDA Label

Normocarb HF Replacement

PrismaSate Dialysate

PrismaSol Replacement

Accusol Dialysate

Duosol Dialysate

NxStage PureFlow Dialysate

• CRRT with citrate regional anticoag

D

R

Putting it All Together: One Approach

• Adjust blend, change saline if indicated

• DIALYSATE: commercial bicarb-based solution

• REPLACEMENT: normal saline

On-Line Dialysate with SLED: An Alternative to Solutions in CRRT

• Extended sessions using standard dialysis equipment

• Dialysate made on-line from concentrates

• Simple, convenient, MUCH cheaper

• Dialysate is not sterile

Citrasate(Advanced Renal Technologies)

• “A” concentrate for dialysis

• Liquid or bulk powder

• Citrate used as acidifying agent

• Local anticoagulation greatly reduces need for heparin

CRRT Solutions: Summary• Solutions needed to maximize clearance

• Bicarbonate has superseded lactate

• Industry-made solutions are available including some approved for replacement

• Pre-mixed, sterile solutions for CRRT are simple, safe, may be costly

• On-line dialysate for SLED is clean (not sterile), simple, cheap

• The best “solution” may still be pending

Thanks!