Pediatric CRRT: Terminology and Physiology Jordan M. Symons, MD University of Washington School of Medicine Seattle Children’s Hospital

Continuous Renal Replacement Therapy CRRT: What is it? Strict definition: any form of kidney dialysis therapy that operates continuously, rather than intermittently More common definition: continuous hemofiltration technique, often used for hemodynamically unstable patients Continuous Renal Replacement Therapy

Current Nomenclature for CRRT SCUF: Slow Continuous Ultrafiltration CVVH: Continuous Veno-Venous Hemofiltration CVVHD: Continuous Veno-Venous Hemodialysis CVVHDF: Continuous Veno-Venous Hemodiafiltration

Basis for CRRT Nomenclature C VV H Rate/Interval for Therapy Blood Access Method for Solute Removal

Solute Removal Mechanisms in RRT Diffusion transmembrane solute movement in response to a concentration gradient importance inversely proportional to solute size Convection transmembrane solute movement in association with ultrafiltered plasma water (“solvent drag”) mass transfer determined by UF rate (pressure gradient) and membrane sieving properties importance directly proportional to solute size

Diffusion

Convection

Clearance: Convection vs. Diffusion

CRRT Schematic R SCUF CVVH UF D CVVHD CVVHDF

Rate Limitations of Volume Removal BP Extra-Vascular Compartment Vascular Compartment

Improved Volume Removal with Slower Ultrafiltration Rates Vascular Compartment Extra-Vascular Compartment BP Stable

CRRT for Metabolic Control

Hollow Fiber Hemofilter

Hemofiltration Membranes Capillary Cross Section Blood Side

Hemofilter Characteristics Pore size “High Flux” vs. “High cut-off” Surface area; porosity Effects on maximum ultrafiltration capacity Membrane material polysulfone, PAN, etc.; modifications Adsorption Prime volume

Effect of Pore Size on Membrane Selectivity Creatinine 113 D Urea 60 D Glucose 180 D Vancomycin ~1,500 D IL-6 ~25,000 D Albumin ~66,000 D

Effect of Pore Size on Membrane Selectivity Creatinine 113 D Urea 60 D Glucose 180 D Vancomycin ~1,500 D IL-6 ~25,000 D These effects are maximized in convection Albumin ~66,000 D

Other Membrane Characteristics: e.g., Charge - Negative charge on membrane: Negatively charged particles may be repelled, limiting filtration - - - -

Other Membrane Characteristics: e.g., Charge - Negative charge on membrane: Negatively charged particles may be repelled, limiting filtration Positively charged particles may have increased sieving + + + +

Other Membrane Characteristics: e.g., Charge - Negative charge on membrane: Negatively charged particles may be repelled, limiting filtration Positively charged particles may have increased sieving Charge may change adsorption

Blood Flow and Dialyzer Have Major Impact on Intermittent HD Clearance Dialyzer 2: Higher K0A Dialyzer 1: Lower K0A Dialysate flow rate (QD) always exceeds QB

Solution/Effluent Flow Rate is Limiting Factor in CRRT QR 600ml/hr QB 150ml/min QD 600ml/hr Effluent 1200ml/hr +

Solution/Effluent Flow Rate is Limiting Factor in CRRT QR 1000ml/hr QB 150ml/min QD 1000ml/hr Effluent 2000ml/hr +

Patient’s Chemical Balance on CRRT Approximates Delivered Fluids Diffusion: blood equilibrates to dialysate Convection: loss is isotonic; volume is “replaced” Consider large volumes for other fluids (IVF, feeds, meds, etc.) Watch for deficits of solutes not in fluids

Small molecules diffuse easily Larger molecules diffuse slowly Diffusion Small molecules diffuse easily Larger molecules diffuse slowly Dialysate required Concentration gradient Faster dialysate flow increases mass transfer

Small/large molecules move equally Limit is cut-off size of membrane 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 Net Pressure H2O H2O H2O H2O

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

Pediatric CRRT Terminology and Physiology: Summary CRRT comes in several flavors SCUF, CVVH, CVVHD, CVVHDF Solute transport: diffusion/convection UF approximates 1-compartment model Membrane characteristics affect therapy Fluid composition, rates drive clearance Advancing technology provides more options

One of the first infants to receive CRRT Vicenza, 1984