Solute Mass Transfer in CRRTGarred et al., AJKD 1997

Post-Dilution CVVH CVVHD

Pre-Dilution CVVH CVVHDF

Qb

Qb Qb

Qb

Qeff Qeff

QeffQeff Qd

Qd

Qr

Qr

Qr

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

Solute Clearance in CRRT

• CVVHD

K = E . QD

• Post-Dilution CVVH

K = S . QUF

• Pre-Dilution CVVH

K = S . QUF .

E =

S =

Concentration in effluent dialysate

Concentration in blood

Concentration in blood

Concentration in filtrate

(

(

)

)

QP

QP + QR

( )

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

Urea Clearance in Pre-Dilution CVVHBrunet et al., AJKD 1999

= -15%

QUF (mL/h)

28.7

33.9

Cle

ara

nce

(m

L/m

in)

Effect of Dialysate Flow Rate onSmall Solute Clearances in CVVHD

Bonnardeaux et al., AJKD 1992

0

20

40

60

80

0 16.7 33.3 50 66.7

Cle

ara

nce

or

Flo

w R

ate

(m

L/m

in)

Creatinine

Urea

Inlet QD (mL/min)

Ultrafiltration

Dialysate Out

Effect of Dialysate Flow Rate onSolute Equilibration in CVVHD

Bonnardeaux et al., AJKD 1992

0.5

0.6

0.7

0.8

0.9

1.0

1.1

0 16.7 33.3 50 66.7

D/P

Ra

tio

Creatinine

Urea

Inlet QD (mL/min)

Solute Equilibration in CVVHDBrunet et al., AJKD 1999

QE (mL/h)

Cle

ara

nce

(m

L/m

in)

Components of Small Solute Clearance in CRRTSigler et al., AJKD 1987

0

5

10

15

20

25

30

35

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Ure

a c

lea

ran

ce, c

c/m

in

Ultrafiltration, (QF)cc/min

Urea and Creatinine Kinetic Parameters in ARF Patients

Leblanc 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

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

Factors Influencing RRT Dose in ARF

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

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

Effect of CVVH on Hemodynamic Parametersin Septic Patients

De Vriese et al., JASN 1999

Time (hours)

Ca

rdia

c o

utp

ut (

l/min

)a

nd P

AO

P (

mm

Hg)

Syste

mic V

ascula

r Re

sistance

(dyn

e.s/cm

5)

Effect of Filter Pore Size on Survivalin Experimental SepsisLee et al., Crit Care Med 1998

8

7

6

5

4

3

2

1

0

120 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192

Nu

mb

er o

f A

nim

als

Aliv

e

Survival Time (hr)