CVVH vs CVVHDCVVH vs CVVHDDoes it Matter?Does it Matter?

Patrick D. Brophy MDPatrick D. Brophy MDUniversity of Michigan University of Michigan Pediatric NephrologyPediatric Nephrology

OBJECTIVESOBJECTIVESDefinitionsDefinitions– CVVH vs CVVHDCVVH vs CVVHD

Mechanisms of actionMechanisms of action– Convective vs Diffusive clearanceConvective vs Diffusive clearance

Other Issues & Selective data review Other Issues & Selective data review – Drug Clearance, membranes & patients, anticoagDrug Clearance, membranes & patients, anticoag

Implementation of one modality over another-Implementation of one modality over another-RationaleRationale– Sepsis vs ARF vs Toxic ingestionsSepsis vs ARF vs Toxic ingestions– Advantages and Disadvantages, expertiseAdvantages and Disadvantages, expertise

DefinitionsDefinitions

Continuous Venous Venous HemofiltrationContinuous Venous Venous HemofiltrationMimics the process which occurs in the Mimics the process which occurs in the

mammalian kidneymammalian kidneyDescribes an almost exclusive convective Describes an almost exclusive convective

treatment with highly permeable membranestreatment with highly permeable membranesUltrafiltrate produced is replaced by a sterile Ultrafiltrate produced is replaced by a sterile

solution (High UF rates)solution (High UF rates)Patient weight loss results from the difference Patient weight loss results from the difference

between ultrafiltration and reinfusion ratesbetween ultrafiltration and reinfusion rates

DefinitionsDefinitionsContinuous Venous Venous HemodialysisContinuous Venous Venous Hemodialysis

Describes a predominantly diffuse treatment Describes a predominantly diffuse treatment in which blood and dialysate are circulated in which blood and dialysate are circulated either side of the dialysis membrane in either side of the dialysis membrane in countercurrent directions.countercurrent directions.

Dialysate may be custom or commercially Dialysate may be custom or commercially producedproduced

The ultrafiltration rate is approximately equal The ultrafiltration rate is approximately equal to the scheduled weight loss (lower UF rate).to the scheduled weight loss (lower UF rate).

DefinitionsDefinitions

Post-Dilution CVVH CVVHD

Pre-Dilution CVVH CVVHDF

Qb

Qb Qb

Qb

Qeff Qeff

QeffQeff Qd

Qd

Qr

Qr

Qr

Mechanisms of ActionMechanisms of Action

CVVHCVVHConvectionConvection

Solute is removed by “Solvent Drag”. The solvent Solute is removed by “Solvent Drag”. The solvent carries the solute (plasma water) through a semi-carries the solute (plasma water) through a semi-permeable membrane.permeable membrane.

The Roller Pump creates Hydrostatic Pressure, The Roller Pump creates Hydrostatic Pressure, which drives the solvent through the membrane.which drives the solvent through the membrane.

The membrane pore size limits molecular transferThe membrane pore size limits molecular transferMore efficient removal of larger molecules than More efficient removal of larger molecules than

diffusiondiffusion

Mechanisms of ActionMechanisms of ActionCVVHCVVH

ConvectionConvectionSince it mimics the mammallian kidney its thought Since it mimics the mammallian kidney its thought

to be more “physiologic” and provides better to be more “physiologic” and provides better removal of middle molecules (500-5000 Daltons) removal of middle molecules (500-5000 Daltons) thought to be responsible for uremia.thought to be responsible for uremia.

With the advent of highly porous membranes need With the advent of highly porous membranes need to use larger markers (500-50000 Daltons) to to use larger markers (500-50000 Daltons) to determine “uremic clearance”.determine “uremic clearance”.

Enhanced clearance of autologous cytokines- Enhanced clearance of autologous cytokines- thought to be involved in Septic Inflammatory thought to be involved in Septic Inflammatory Response Syndrome (SIRS).Response Syndrome (SIRS).

Mechanisms of ActionMechanisms of Action

CVVHCVVHConvectionConvection

Sieving Coefficient- clearance coefficient for Sieving Coefficient- clearance coefficient for hemofiltration defined by UV/Phemofiltration defined by UV/P

U= Filtrate ConcentrationU= Filtrate ConcentrationV= VolumeV= VolumeP= Mean plasma concentration over the clearance periodP= Mean plasma concentration over the clearance period

SC is 1 for molecules that pass through the SC is 1 for molecules that pass through the membrane easily & 0 for those that do notmembrane easily & 0 for those that do not

Mechanisms of ActionMechanisms of Action

CVVHDCVVHDDiffusion (predominantly)Diffusion (predominantly)

Solute diffuses down an electrochemical gradient Solute diffuses down an electrochemical gradient through a semi-permeable membrane in response through a semi-permeable membrane in response to an electrolyte solution running counter current to to an electrolyte solution running counter current to the blood flow through the filter.the blood flow through the filter.

Diffusive movement occurs via Brownian motion of Diffusive movement occurs via Brownian motion of the solute- smaller molecules (ie urea) have greater the solute- smaller molecules (ie urea) have greater kinetic energy and are preferentially removed kinetic energy and are preferentially removed based on the size of the concentration gradientbased on the size of the concentration gradient

Mechanisms of ActionMechanisms of Action

CVVHDCVVHDDiffusion (predominantly)Diffusion (predominantly)

Some convection occurs due to prescribed UF and Some convection occurs due to prescribed UF and if High flux filters are utilizedif High flux filters are utilized

Solute removal is proportional to the concentration Solute removal is proportional to the concentration gradient and size of each moleculegradient and size of each molecule

Dialysate flow rate is slower than BFR and is the Dialysate flow rate is slower than BFR and is the limiting factor to solute removallimiting factor to solute removal

Solute removal is directly proportional to dialysate Solute removal is directly proportional to dialysate flow rate flow rate

Mechanisms of ActionMechanisms of Action

CVVHDCVVHDDiffusion (predominantly)Diffusion (predominantly)

Diffusion Coefficient- clearance coefficient for Diffusion Coefficient- clearance coefficient for hemodialysis defined by UV/Phemodialysis defined by UV/P

U= Dialysate (+Filtrate) ConcentrationU= Dialysate (+Filtrate) ConcentrationV= VolumeV= VolumeP= Mean plasma concentration over the clearance P= Mean plasma concentration over the clearance

periodperiodPrinciple same as for SC with 1= to optimal Principle same as for SC with 1= to optimal

clearance and 0= to no (minimal clearance)clearance and 0= to no (minimal clearance)

Other IssuesOther Issues

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

Other IssuesOther Issues

Low molecular weight solutesLow molecular weight solutesMiddle/High molecular weight solutesMiddle/High molecular weight solutesDrug/Toxin ClearanceDrug/Toxin ClearanceImpact on Adsorptive membrane Impact on Adsorptive membrane characteristicscharacteristicsAnticoagulationAnticoagulationPatient CharacteristicsPatient Characteristics

Low Molecular Weight SolutesLow Molecular Weight Solutes

Relative equivalence of convective and Relative equivalence of convective and diffusive clearances (membrane variation diffusive clearances (membrane variation and design)and design)

Solute Molecular Weight Solute Molecular Weight and clearanceand clearance

Jeffrey Jeffrey et al.,et al., Artif Organs 1994 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 Diffusive & Convective Solute Clearances During CRRTClearances During CRRTBrunet et.al AJKD 34:1999Brunet et.al AJKD 34:1999

Evaluated convective & dialysate Evaluated convective & dialysate clearance of :clearance of :

UREAUREACreatinineCreatininePhosphatePhosphateUratesUratesBB22microglobulinmicroglobulin

Variety of UF & Dialysate Flows with Multiflow60 Variety of UF & Dialysate Flows with Multiflow60 &100 membranes&100 membranes

CVVH vs CVVHD continuedCVVH vs CVVHD continued

Conclusions:Conclusions:At QAt QUFUF with predilution (2L/hr) FRF 15-20% reduction with predilution (2L/hr) FRF 15-20% reduction in urea, urates & creatininein urea, urates & creatinineSC= 1 for all small molecules for CVVH-both filtersSC= 1 for all small molecules for CVVH-both filtersM100>M60 (QM100>M60 (QDD 1.5-2.5L/hr) diffusive clearance with 1.5-2.5L/hr) diffusive clearance with the difference increasing as molecular weight the difference increasing as molecular weight increasedincreasedQQDD > 1.5L/hr poor diffusive middle molecule clearance > 1.5L/hr poor diffusive middle molecule clearance (both membranes); whereas increasing nonlinear (both membranes); whereas increasing nonlinear clearance occurred with convection as Qclearance occurred with convection as QUFUF increased increased for both filtersfor both filters

CVVH vs CVVHD continuedCVVH vs CVVHD continued

No additive effect with combination No additive effect with combination dialysate & FRF therapy for middle dialysate & FRF therapy for middle molecule clearancemolecule clearanceAuthors conclude:Authors conclude:– ““Convection more efficient than diffusion in Convection more efficient than diffusion in

removing mixed- molecular- weight solutes removing mixed- molecular- weight solutes during CRRT”during CRRT”

Drug & Toxin ClearanceDrug & Toxin Clearance

Drug/Toxin ClearanceDrug/Toxin Clearance– Molecular WeightMolecular Weight– Protein BindingProtein Binding– VdVd– Membrane compositionMembrane composition

As MW increases diffusive drug clearance As MW increases diffusive drug clearance declines more than convective clearancedeclines more than convective clearance

Adsorptive Membrane Adsorptive Membrane CharacteristicsCharacteristics

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

Adsorptive Membrane Adsorptive Membrane CharacteristicsCharacteristics

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

AnticoagulationAnticoagulation

Citrate use- centers relatively confined to Citrate use- centers relatively confined to diffusive therapy (works well with diffusive therapy (works well with CVVHDF)CVVHDF)– Citrate: multiple protocols for CVVHDCitrate: multiple protocols for CVVHD

Few for CVVH (Niles et.al. 2002-CRRT abstract) Few for CVVH (Niles et.al. 2002-CRRT abstract) where citrate included in FRFwhere citrate included in FRF

Heparin- both CVVH & CVVHDHeparin- both CVVH & CVVHD

Patient CharacteristicsPatient Characteristics

Etiology underlying the patient’s can help Etiology underlying the patient’s can help determine choice of therapydetermine choice of therapy– Speculative benefit of CVVH in Sepsis, Toxin Speculative benefit of CVVH in Sepsis, Toxin

removal (although filter impact very important)removal (although filter impact very important)– For ARF & Fluid overload little difference is For ARF & Fluid overload little difference is

likely likely

No Definitive demonstration of superiority No Definitive demonstration of superiority of one over the otherof one over the other

Final Thoughts & SummaryFinal Thoughts & Summary

Currently- no data to prove outcome Currently- no data to prove outcome superior with either modalitysuperior with either modalityBest to use what each center is most Best to use what each center is most comfortable withcomfortable withAcute Dialysis Quality Initiative (ADQI) Acute Dialysis Quality Initiative (ADQI) Guidelines reflect these ongoing study Guidelines reflect these ongoing study requirements and recommendationsrequirements and recommendationsPlenty of work to do!!!!Plenty of work to do!!!!

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS– MELISSA GREGORYMELISSA GREGORY– ANDREE GARDNERANDREE GARDNER– JOHN GARDNERJOHN GARDNER– THERESA MOTTESTHERESA MOTTES– TIM KUDELKATIM KUDELKA– LAURA DORSEY & BETSY ADAMSLAURA DORSEY & BETSY ADAMS

(p. brophy)