Solute Mass Transfer in CRRT Garred et al., AJKD 1997

1. Post-Dilution CVVH CVVHD Qr Qb Qb Qeff Qeff Qd Qr Qr Qb Qb Qeff Qeff Qd Pre-Dilution CVVH CVVHDF Solute Mass Transfer in CRRTGarred et al., AJKD 1997

2. Mechanisms of Solute Removal: IHD vs CRRTClark and Ronco, Kidney Int 1998 IHD CRRT Small Solutes Diffusion* Diffusion** (CVVHD)(mw < 300) Convection (CVVH) Middle Molecules Diffusion Convection(mw 500-5,000) Convection Diffusion LMW Proteins Convection Convection(mw 5,000-50,000) Diffusion Adsorption Adsorption Large Proteins Convection Convection(mw > 50,000) * Determinants: flow rates, membrane thickness** Determinants: effluent dialysate flow rate

3. QP ( ) QP +QR Solute Clearance in CRRT Concentration in effluent dialysate ( ) E = • CVVHD K = E . QD • Post-Dilution CVVH K = S . QUF • Pre-Dilution CVVH K = S . QUF . Concentration in blood Concentration in filtrate ( ) S = Concentration in blood

4. Dialytic Solute Removal Mechanisms • 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 rate determined by ultrafiltration rate (pressure gradient) and membrane sieving properties • importance directly proportional to solute size

5. 33.9 28.7  = -15% QUF (mL/h) Urea Clearance in Pre-Dilution CVVHBrunet et al., AJKD 1999 Clearance (mL/min)

6. Effect of Dialysate Flow Rate onSmall Solute Clearances in CVVHDBonnardeaux et al., AJKD 1992 Dialysate Out Urea Clearance or Flow Rate (mL/min) Creatinine Ultrafiltration Inlet QD (mL/min)

7. D/P Ratio Urea Creatinine Inlet QD (mL/min) Effect of Dialysate Flow Rate onSolute Equilibration in CVVHDBonnardeaux et al., AJKD 1992

8. Solute Equilibration in CVVHDBrunet et al., AJKD 1999 Clearance (mL/min) QE (mL/h)

9. Components of Small Solute Clearance in CRRTSigler et al., AJKD 1987 Urea clearance, cc/min Ultrafiltration, (QF)cc/min

10. Urea and Creatinine Kinetic Parameters in ARF PatientsLeblanc et al., AJKD 1998 nPCR (gm/kg/d) 1.75 ± 0.82 Creatinine Index (mg/kg/d) 13.7 ± 4.7 LBM (kg) 38.3 ± 11.9 LBM/BW (%) 49.5 ± 14.0

11. Effect of Solute Molecular Weight on EquilibrationJeffrey et al., Artif Organs 1994 Solute (MW) Sieving Coefficient (HF) Diffusion Coefficient (HD) Urea (60) 1.01 ± 0.05 1.01 ± 0.07 Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06 Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04* Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04** *P<0.05 vs sieving coefficient**P<0.01 vs sieving coefficient

12. Factor CRRT vs IHD K . t Favors CRRT (due to “t”) Anticoagulation Favors IHD Hypotension Favors CRRT Compartment Effects Favors CRRT Access Recirculation Favors CRRT “Down-Time” Favors IHD Defined Target Favors Neither Factors Influencing RRT Dose in ARF

13. Prescribed vs Delivered RRT in ARF • CRRT • “Down-time”: procedures, filter changes • Decline in filter performance:  SC or CDo/CBi, UFR • Access recirculation • IHD • Failure to achieve prescription (QB, time) • Compartment effects (rebound) • Access recirculation

14. Effect of CVVH on Hemodynamic Parametersin Septic PatientsDe Vriese et al., JASN 1999 Cardiac output (l/min)and PAOP (mm Hg) Systemic Vascular Resistance(dyne.s/cm5) Time (hours)

15. 8 7 6 5 4 Number of Animals Alive 3 2 1 0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 Survival Time (hr) Effect of Filter Pore Size on Survivalin Experimental SepsisLee et al., Crit Care Med 1998