2 CVVH vs CVVHD Does it Matter? Patrick D. Brophy MDUniversity of Michigan Pediatric Nephrology
3 OBJECTIVES Definitions Mechanisms of action CVVH vs CVVHDMechanisms of actionConvective vs Diffusive clearanceOther Issues & Selective data reviewDrug Clearance, membranes & patients, anticoagImplementation of one modality over another-RationaleSepsis vs ARF vs Toxic ingestionsAdvantages and Disadvantages, expertise
4 Definitions Continuous Venous Venous Hemofiltration Mimics the process which occurs in the mammalian kidneyDescribes an almost exclusive convective treatment with highly permeable membranesUltrafiltrate 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 producedThe ultrafiltration rate is approximately equal to the scheduled weight loss (lower UF rate).
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 transferMore 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/PU= Filtrate ConcentrationV= VolumeP= Mean plasma concentration over the clearance periodSC 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 utilizedSolute removal is proportional to the concentration gradient and size of each moleculeDialysate flow rate is slower than BFR and is the limiting factor to solute removalSolute removal is directly proportional to dialysate flow rate
12 Mechanisms of Action CVVHD Diffusion (predominantly) Diffusion Coefficient- clearance coefficient for hemodialysis defined by UV/PU= Dialysate (+Filtrate) ConcentrationV= VolumeP= Mean plasma concentration over the clearance periodPrinciple same as for SC with 1= to optimal clearance and 0= to no (minimal clearance)
13 Other IssuesThe 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 solutesDrug/Toxin ClearanceImpact on Adsorptive membrane characteristicsAnticoagulationPatient 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 1994Solute (MW) Sieving Coefficient Diffusion CoefficientUrea (60) 1.01 ± ± 0.07Creatinine (113) 1.00 ± ± 0.06Uric 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 34:1999Evaluated convective & dialysate clearance of :UREACreatininePhosphateUratesB2microglobulinVariety 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 & creatinineSC= 1 for all small molecules for CVVH-both filtersM100>M60 (QD L/hr) diffusive clearance with the difference increasing as molecular weight increasedQD > 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 clearanceAuthors conclude:“Convection more efficient than diffusion in removing mixed- molecular- weight solutes during CRRT”
20 Drug & Toxin Clearance Drug/Toxin Clearance Molecular WeightProtein BindingVdMembrane compositionAs 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 AnticoagulationCitrate use- centers relatively confined to diffusive therapy (works well with CVVHDF)Citrate: multiple protocols for CVVHDFew for CVVH (Niles et.al CRRT abstract) where citrate included in FRFHeparin- both CVVH & CVVHD
24 Patient Characteristics Etiology underlying the patient’s can help determine choice of therapySpeculative benefit of CVVH in Sepsis, Toxin removal (although filter impact very important)For ARF & Fluid overload little difference is likelyNo Definitive demonstration of superiority of one over the other
25 Final Thoughts & Summary Currently- no data to prove outcome superior with either modalityBest to use what each center is most comfortable withAcute Dialysis Quality Initiative (ADQI) Guidelines reflect these ongoing study requirements and recommendationsPlenty of work to do!!!!