2. CVVH vs CVVHD Does it Matter?
Patrick D. Brophy MD
University of Michigan Pediatric Nephrology

3. OBJECTIVES Definitions Mechanisms of action
CVVH vs CVVHD
Mechanisms of action
Convective vs Diffusive clearance
Other Issues & Selective data review
Drug Clearance, membranes & patients, anticoag
Implementation of one modality over another-Rationale
Sepsis vs ARF vs Toxic ingestions
Advantages and Disadvantages, expertise

4. Definitions Continuous Venous Venous Hemofiltration
Mimics the process which occurs in the mammalian kidney
Describes an almost exclusive convective treatment with highly permeable membranes
Ultrafiltrate produced is replaced by a sterile solution (High UF rates)
Patient weight loss results from the difference between ultrafiltration and reinfusion rates

5. Definitions Continuous Venous Venous Hemodialysis
Describes a predominantly diffuse treatment in which blood and dialysate are circulated either side of the dialysis membrane in countercurrent directions.
Dialysate may be custom or commercially produced
The ultrafiltration rate is approximately equal to the scheduled weight loss (lower UF rate).

6. Definitions Post-Dilution CVVH CVVHD Pre-Dilution CVVH CVVHDF Qb QeffQd Qr

7. Mechanisms of Action CVVH Convection
Solute is removed by “Solvent Drag”. The solvent carries the solute (plasma water) through a semi-permeable membrane.
The Roller Pump creates Hydrostatic Pressure, which drives the solvent through the membrane.
The membrane pore size limits molecular transfer
More efficient removal of larger molecules than diffusion

8. Mechanisms of Action CVVH Convection
Since it mimics the mammallian kidney its thought to be more “physiologic” and provides better removal of middle molecules ( Daltons) thought to be responsible for uremia.
With the advent of highly porous membranes need to use larger markers ( Daltons) to determine “uremic clearance”.
Enhanced clearance of autologous cytokines- thought to be involved in Septic Inflammatory Response Syndrome (SIRS).

9. Mechanisms of Action CVVH Convection
Sieving Coefficient- clearance coefficient for hemofiltration defined by UV/P
U= Filtrate Concentration
V= Volume
P= Mean plasma concentration over the clearance period
SC is 1 for molecules that pass through the membrane easily & 0 for those that do not

10. Mechanisms of Action CVVHD Diffusion (predominantly)
Solute diffuses down an electrochemical gradient through a semi-permeable membrane in response to an electrolyte solution running counter current to the blood flow through the filter.
Diffusive movement occurs via Brownian motion of the solute- smaller molecules (ie urea) have greater kinetic energy and are preferentially removed based on the size of the concentration gradient

11. Mechanisms of Action CVVHD Diffusion (predominantly)
Some convection occurs due to prescribed UF and if High flux filters are utilized
Solute removal is proportional to the concentration gradient and size of each molecule
Dialysate flow rate is slower than BFR and is the limiting factor to solute removal
Solute removal is directly proportional to dialysate flow rate

12. Mechanisms of Action CVVHD Diffusion (predominantly)
Diffusion Coefficient- clearance coefficient for hemodialysis defined by UV/P
U= Dialysate (+Filtrate) Concentration
V= Volume
P= Mean plasma concentration over the clearance period
Principle same as for SC with 1= to optimal clearance and 0= to no (minimal clearance)

13. Other Issues
The greatest difference between modalities is likely the impact of the membrane utilized and their specific characteristics.
There are no data available assessing patient outcomes using diffusive (CVVHD) and convective (CVVH) therapies

14. Other Issues Low molecular weight solutes
Middle/High molecular weight solutes
Drug/Toxin Clearance
Impact on Adsorptive membrane characteristics
Anticoagulation
Patient Characteristics

15. Low Molecular Weight Solutes
Relative equivalence of convective and diffusive clearances (membrane variation and design)

16. Solute Molecular Weight and clearance Jeffrey et al
Solute Molecular Weight and clearance Jeffrey et al., Artif Organs 1994
Solute (MW) Sieving Coefficient Diffusion Coefficient
Urea (60) 1.01 ± ± 0.07
Creatinine (113) 1.00 ± ± 0.06
Uric Acid (168) 1.01 ± ± 0.04*
Vancomycin (1448) 0.84 ± ± 0.04**
*P<0.05 vs sieving coefficient **P<0.01 vs sieving coefficient

17. Diffusive & Convective Solute Clearances During CRRT Brunet et
Diffusive & Convective Solute Clearances During CRRT Brunet et.al AJKD 34:1999
Evaluated convective & dialysate clearance of :
UREA
Creatinine
Phosphate
Urates
B2microglobulin
Variety of UF & Dialysate Flows with Multiflow60 &100 membranes

18. CVVH vs CVVHD continued
Conclusions:
At QUF with predilution (2L/hr) FRF 15-20% reduction in urea, urates & creatinine
SC= 1 for all small molecules for CVVH-both filters
M100>M60 (QD L/hr) diffusive clearance with the difference increasing as molecular weight increased
QD > 1.5L/hr poor diffusive middle molecule clearance (both membranes); whereas increasing nonlinear clearance occurred with convection as QUF increased for both filters

19. CVVH vs CVVHD continued
No additive effect with combination dialysate & FRF therapy for middle molecule clearance
Authors conclude:
“Convection more efficient than diffusion in removing mixed- molecular- weight solutes during CRRT”

20. Drug & Toxin Clearance Drug/Toxin Clearance
Molecular Weight
Protein Binding Vd
Membrane composition
As MW increases diffusive drug clearance declines more than convective clearance

21. Adsorptive Membrane Characteristics
Biocompatible membranes appear to have greater adsorptive properties than less biocompatible membranes (PAN>Polysulfone)
Filter Characteristics for small molecule removal include: pore size distribution & density and surface area and at conventional flow rates (in adults-2L or less) clearance is flow rate dependent.
As molecular size increases: hydraulic permeability & adsorption capacity become important.

22. Adsorptive Membrane Characteristics
No specific Membrane recommendations as no studies to definitively prove superior performance under specific modality

23. Anticoagulation
Citrate use- centers relatively confined to diffusive therapy (works well with CVVHDF)
Citrate: multiple protocols for CVVHD
Few for CVVH (Niles et.al CRRT abstract) where citrate included in FRF
Heparin- both CVVH & CVVHD

24. Patient Characteristics
Etiology underlying the patient’s can help determine choice of therapy
Speculative benefit of CVVH in Sepsis, Toxin removal (although filter impact very important)
For ARF & Fluid overload little difference is likely
No Definitive demonstration of superiority of one over the other

25. Final Thoughts & Summary
Currently- no data to prove outcome superior with either modality
Best to use what each center is most comfortable with
Acute Dialysis Quality Initiative (ADQI) Guidelines reflect these ongoing study requirements and recommendations
Plenty of work to do!!!!

26. ACKNOWLEDGEMENTS MELISSA GREGORY ANDREE GARDNER JOHN GARDNER
(p. brophy)
ACKNOWLEDGEMENTS
MELISSA GREGORY
ANDREE GARDNER
JOHN GARDNER
THERESA MOTTES
TIM KUDELKA
LAURA DORSEY & BETSY ADAMS