CVVH vs CVVHD Does it Matter?

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

3. OBJECTIVES • Definitions • 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. Post-Dilution CVVH CVVHD Qr Qb Qb Qeff Qeff Qd Qr Qr Qb Qb Qeff Qeff Qd Pre-DilutionCVVH CVVHDF Definitions

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 (500-5000 Daltons) thought to be responsible for uremia. • With the advent of highly porous membranes need to use larger markers (500-50000 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 clearanceJeffrey et al., Artif Organs 1994 Solute (MW) Sieving Coefficient Diffusion Coefficient 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

17. Diffusive & Convective Solute Clearances During CRRTBrunet 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 1.5-2.5L/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. 2002-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 THERESA MOTTES TIM KUDELKA LAURA DORSEY & BETSY ADAMS (p. brophy)