ContinuousRenalReplacementTherapy AnnualRefresherCourseinCRITICALCAREMcGillCourseDirector PeterGoldberg MDDidierPayenCCDivision DeptofAnesthesiology13 4 2000 Content PhysicalprinciplesDefinitionsTechniquesClinicalissuesSupportivetherapyoractivetherapy SepsisanexampleWhy How Forwhatgoal PHYSICALPRINCIPLES DEFINITIONS 30000Da 30000Da 65000Da 65000Da PTM CONVECTION 30000Da 30000Da 65000Da 65000Da PTM CONVECTION 30000Da 30000Da 65000Da 65000Da PTM CONVECTION 30000Da 30000Da 65000Da 65000Da PTM CONVECTION 30000Da 30000Da 65000Da 65000Da Cd Csang Pdialysat Pblood Progressiveequilibriumofthe plasma and dial ONLYSMALLMOLECULESCROSSTHEMBNE DIFFUSION 30000Da 30000Da 65000Da 65000Da Cd Csang DIFFUSION Pdialysat Pblood 30000Da 30000Da 65000Da 65000Da Cd Csang DIFFUSION Pdialysat Pblood 30000Da 30000Da 65000Da 65000Da Cd Csang DIFFUSION Pdialysat Pblood 30000Da 30000Da 65000Da 65000Da Filtration substitution Blood FILTRATIONRATE0TO2L Hr SCUF CVVH DEFINITIONSBELLOMOetal AmJKidneyDis 28 Suppl3 1996 SCUF UseonlyforfluidcontrolinoverhydratedstatusCVVH Theultrafiltrateproducedduringmembranetransitisreplacedinpartorcompletelytoachievebloodpurificationandvolumecontrol UFisinexcessifweightlossismandatory clearanceofsolutesequalsUFCVVHD continuoushemodialysis countercurrentflowofdialysissolution Bothdiffusion convectionEfficiencyislimitedtosmallmolecules lowPermfilter CVVHDF same Bothdiffusion convectionbuthigherdialysateflow HighPermfilter SCUFSlowContinuousUltrafiltration MaximumPt Fluidremovalrate 2000ml h Therapyoptions CVVHContinuousVeno VenousHemofiltration MaximumPt Fluidremovalrate 1000ml h Therapyoptions CVVHDContinuousVeno VenousHemodialysis MaximumPt fluidremovalrate 1000ml h TherapyOptions CVVHDFContinuousVeno VenousHemodiafiltration MaximumPt Fluidremovalrate 1000ml h Therapyoptions Replacement EFFICIENCY CLINICALISSUES CLINICALINDICATIONS IHDvsCRRT norandomizedtrialsbutinferiorityofIHDmanisfestsitselfatmanylevels HemodynamicstabilityHypotension volumecontrolUremiccontrol withCRRTthanIHD ClarketalJASNephrol 1994 Metaboliccontrol metabolicacidosis phosphatelevelsInICUpatientsCRRTpreventsthesurgeinICPCardiacdiseaserestoredrybodyweight improveVflowCardiacsurgicalpatientsoptimizationbetweenfunctionandpreloadSepsisandinflammatorypatients CRRTANDINFLAMMATIONSepsisanexample HYPOTHESISFORMODSPREVENTION ControloftissueedemaEDTXadsorptionImmunomodulation CAVHafterStaphAureusinswine LeePAetal CritCareMed1993 21 914 924 Goals 1 CAVHimpactonmorbidityandmortality2 IfUFcontainsmediatorsDesign prospective randomized controlled n 65 Staphaureus 8x109CFU over1hrPart1 Group1 5 5 plasmafiltrationfractionGroup2 16 6 Group3 33 4 ControlcleanUFPart2 UFiltrateconcentratefromeachgroupinfusedintohealthypigs CAVHafterStaphAureusinswine LeePAetal CritCareMed1993 21 914 924 Measurementsandresults InG1 2 3 thesurvivalrateincreasedinrelationtoFFincomparisonwithcontrolUFconcentrateinjectionledtoanimaldeathsimilarlytoStaphaureusincontrolgroup Conclusion CAVH improvedsurvivalratemightberelatedtomediatorsremoval EDTX HEMOFILTRATION Invivoexperimentalstudies 1 Steinetal Intens CareMed 1991pigmodel LPSinjectionmembrane polysulfone zerobalancedHFdecreaseinPVR EVLW othermechanismsthanwaterbalance EDTX HEMOFILTRATION Invivoexperimentalstudies 2 Gomezetal Anesthesiology 1990dogmodel aliveEcoli invitrostudycuprophanemembraneCHFreversedmyocardialdepressionsepticseradepressedexvivomyocardialcontraction aneffectwhichispreventedbyCHF removalofcardio depressivesubstances EDTX HEMOFILTRATION Invivoexperimentalstudies Grootendorstetal J Crit Care 1993 Endotoxinshockinpigs Polysulfonemembrane UltrafiltratecontainsfiltrablefactorsthatincreasePapanddepresscardiacperformanceinhealthyanimalsMateoetal Am Resp J Crit CareMed 1993 1994 Rabbitendotoxinicshockmodel AN69adaptedcircuit Hemo adsorptiononly pre EDTXinjection Noresuscitation AoBF Pas HR EDTXclearance TNF exvivovascularreactivity FromMateoetalAJR CCM1996 Abst FromMateoetalAJR CCM1996 Abst TIME min TNF levels p 0 05 U I ML 6000 8000 10000 LPS LPS HAD E U ML 0 2000 4000 TIME min 3000 1000 EDTXlevels FromMateoetalAJR CCM1996 Abst NE CLPmodelofacuteperitonitisinpig24hrsofCAVHvsnoCAVHexvivotestofPMNphagocytosisforCandida T0 T24 48 72H hemodynamic gazometric biologicdata CAVHATTENUATESPMNPHAGOCYTOSISINPORCINEMODELOFPRITONITISA DiScipioetal AmJSurg 173 1997 CAVHATTENUATESPMNPHAGOCYTOSISINPORCINEMODELOFPERITONITIS A DiScipioetal AmJSurg 173 1997 RESULTSNodifferenceinhemodynamic gasometricparametersbetweenCAVH controlCAVHdecreasesintensityofPMNphagocytosis opsonisation andPMNhyperactivityuntiltheearlyphaseofsepsis Extensiveactivationofinflammatoryresponses mediators vasoactive cardiodepressant organdysfunction SupportiveTherapies Symptomatic Symptomatic MediatorRegulation HF Removalofinflammatorymediators Fluidbalancecontrol Metabolicstatuscontrol CHANGEINMORTALITY PEEPventilationHemodialysis persistantSIRS MODS CONVECTIVEELIMINATIONOFCYTOKINES Theconceptof thetipoftheiceberg JMCavaillon Plasmaelevationofcytokines saturationof OrigincellsTargetcellsExtracellularcompartmentPlasmaremovalmayhavethensmalleffectintermoftissue celllevelsofcytokines CONVECTIVEELIMINATIONOFCYTOKINES NodropinserumlevelsofILexceptIL 1MorerapidproductionthaneliminationShiftofILfromthetissuestotheserumHighvolumehemofiltration CoupledHVHF HADsorption Eliminationofinflammatorymediatorsbyhemofiltration mediatoreliminationchangestudyref Bacterialtoxins EndotoxinAdsorption Ex vivo An Vanholder Mat oLipidAAdsorption Ex vivoDinarelloAnaphylatoxins C3aFiltration HumanHoffmannC5aAdsorption HumanHoffmannArachidonicacidderivatives TxB2Filtration AnimalHeidemann6 ketoPGF2Filtration An HumHeideman StaubachCytokines TNFno HumanIL 1bFiltration HumanBellomo HoffmannIL 6no HumanHoffmann MillarIL 8Filtration HumanHoffmann MillarMyocardialdepressingfactor Filtration An Hum Coraim Gomez Hallstr m HighvolumeHFinseveresepsis PHonor etal HopStPierre inpressCCM 20Ptsinrefractoryshock PA 2hrsincreaseabout50 forCO 25 SvO2 4hrspHa 7 3 Reduction50 vasoactivedrugs Results 11responders 9survivors 1diedfromMOSFand1fromNosocInfect thenonrespondersdiedat80 Adequatebiocompatibilityblood membraneinteractioninductionofchronicinflammatoryreactionSubstratelosses glucose amino acids HormoneslossesHeatlossCatheter associatedcomplications infectionsCostsNeedforprolongedanticoagulationcoatingsystems Howtolimitadverseeffects CONTROLSTUDIES Substancesinvolved Mechanismsoftheinflammatoryreaction Beforeorafterrenalfailureappearance End points mortality Organfailure Cost benefit design PERSPECTIVES EnhancedadsorptionDefinitionsofcut offsforspecificmoleculesSelectiveornon selectiveremovalAnticoagulationcoatingsystems Materials FacteurD presseurMyocardique L ultrafiltratdesanimauxseptiquesprovoque invivoun tatdechocoudeseffetscomparables l endotoxin mie invitroouexvivouned pressiondelacontractiondesfibresmyocardiquesisol es Aucoursdel insuffisancecardiaque Coraimetal 1995Aucoursduchocseptique Parilloetal 1985 Gomezetal 1990 Grootendorstetal 1993 Leeetal 1993A