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

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

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

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).

Definitions Post-Dilution CVVH CVVHD Pre-Dilution CVVH CVVHDF Qb Qeff Qd Qr

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

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).

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

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

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

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)

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

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

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

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 ± 0.05 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

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

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

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”

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

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.

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

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

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

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!!!!

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