【持续性肾脏替代治疗crrt英文精品课件】dialytic therapy in acute renal failure - low res

DialytictherapyinAcuteRenalFailure startingfromsquareone DrChanChingKitMedicalOfficerRenalUnit DepartmentofMedicine PYNEH Outline BackgroundanddefinitionsModalitiesofdialytictherapyPracticalproblemsindialytictherapyinARF 5wWhytostart Whentostart Whattostart IHD CRRTdilemmaHowtostart anticoagulation choiceofdialyserHowmuchto wash soluteandfluidclearanceandadequacyConclusion Background MortalityinpatientswithARFissurprisinglyhigh andhasnotchangedsignificantlydespiteadvancesinmedicaltechnology introductionofdialysisformorethan30years10 23 ofICUpatientdevelopedARFBrivetetal CritCareMed24 192 198 1996Groneveldetal Nephron59 602 610 199170 requiredrenalreplacementtherapy RRT tosustainlife McCulloughetal AmJMed103 368 375 1997PeriodprevalenceofARFonRRTinICUwas5 6 Uchinoetal JAMA294 813 818 2005 Background Sepsis MODSasleadingcauseforARFInpatientmortalityfrom 30 innephrotoxicdruginducedARFto 90 whenARFisassociatedwithmultipleorganfailure Turneyetal JAMA275 1516 1517Chertowetal ArchInternMed155 1505 1511 1995 Background ARFisanindependentriskfactorformorbidityandmortalityMetnitzetal CritCareMed30 2051 8 2002UraemicstateandtheneedforRRTamongcriticallyillpatientsfrequentlyresultsintherapy relatedcomplications whichmayfurtheraggravatetheunderlyingconditionManagingARFinICUisasignificantongoingchallengetoIntensivistsandNephrologists ACFryetalPostgradMedJ2006 82 106 111 DefinitionofARF WidevariationinquotedfiguresduetonoconsensusdefinitionsforARF Morethan35differentdefinitionshavebeenusedintheliterature creatingconfusionanddifficultiesincomparisonamongdifferentstudies KellumJAetal CurrOpinCritCare8 509 514 2002TheAcuteDialysisQualityInitiative ADQI Developconsensusandevidence basedstatementsinthefieldofARF RIFLECriteria LinearincreaseinoddsratiofromRisktoFailure Oddsratios Risk2 5 Injury5 4 Failure10 1 CritCareMed2006 Vol34No7 1913 1917 PracticalproblemsindialytictherapyinARF Whytostart IndicationsforrenalreplacementtherapyinICURenalAcid basedisturbance mainlymetabolicacidosisElectrolytesdisturbance e ghyperkalaemiaIntoxicationOverloadoffluid e g pulmonaryoedemaUraemiaNon renalAllowingadministrationoffluidsandnutritionEliminationofinflammatorymediators StefanandEckardt SeminarinDialysisvol19 No 6 Nov Dec 2006 p455 464 Whentostart NeedforRRTincriticallyillpatientswithARFdependsonnumerousfactorsRemainingdiuresisAccumulationofuraemicsolutesHypercatabolicstatePatientsizeDesiredlevelofmetaboliccontrol Whentostart Ur Crlevel Ureagenerationisnotconstantbetweenpatients orevenforthesamepatientovertimeVolumeofdistribution V ofureamaychangeovertimeUr Crlevelsdependson ProductionVolumeofdistributionRenaleliminationBloodureanitrogen BUN orserumcreatininelevelsarenotgoodindicatorsofseverityofARFSofarnobiomarkers clinicalpredictorsofthecourseofAKIavailable Benefitsandrisks EarlyinitiationofRRTmayavoidseverederangementsinmetaboliccontrol andsubsequentadverseeffectsofARF Improvementinsurvival RRTmayhavenegativeconsequencese g influencesonimmunesysteme gactivationofneutrophilsorthecomplementsystemPossiblecomplicationsfromRRTe gbleedingcomplication EarlyinitiationofRRT NonrandomizedstudiessuggestedthatbothearlyinitiationofRRTandtheuseofhigherultrafiltrationratesimprovesurvivalandrenalrecoveryInpost traumaticAKI earlyinitiationofCVVH BUN43 13mg dL D10 15 wasassociatedwitha39 survivalwhencomparedto20 3 survivalinlateRRTgroup BUN94 28 D19 27 p 0 05 Gettingsetal IntensiveCareMed25 805 813 1999 EarlyinitiationofRRT EarlyCVVHDF K 5 5 SCr 5mg dLregardlessofurineoutput wasassociatedwithfeverdaysofmechanicalventilation ICUstay aswellaslowerICUandhospitalmortality 17 6and23 5 vs 48 1and55 5 whencomparedtohistoricalcontrol urineoutput84mg dL SCr 3mg dL K 6regardlessofurineoutput ElahietalEurJCardSurg2004 26 1027 1031 EarlyinitiationofRRT HigherdosesofRRTandthereforebetteruraemiccontrolledtoanimprovementofsurvival MeanstartingBUNinpatientswhosurvivedwaslowerthaninnon survivorsinallstudygroupsRoncoetal Lancet356 26 30 2000 EarlyinitiationofRRT NoimprovementinD28survivalandrenalrecovery withtheuseofhighultrafiltrationrateorearlyhemofiltrationinoliguricARFpatients Boumanetal CritCareMed30 2205 2211 2002Diseaseseveritytoolowinthisstudytodemonstratesignificantdifferencebetweenearlyvs lateapproach EarlyinitiationofRRT prophylactic hemofiltrationperformedin24traumapatientsPositiveeffectsonhemodynamicparametersNobenefitwithrespecttotheseverityanddurationofillnessorpatientoutcome Baueretal IntensiveCareMed27 376 383 2001 Valerieetal SeminarindialysisVol17 No1 Jan Feb 2004 p30 36 Confoundingfactors IndicationsforrenalsupportarelikelytobedifferentEarlyinitiationmaybedrivedbyvolumeoverloadorelectrolytedisturbance asopposedtoazotemiainpatientsinlateinitiationgroupInsignificanttrendtowardgreaterdurationoftherapyinlateinitiationgroupMoresevererenalinjuryinlateinitiationgroup leadingtoanincreasedtimetorecoveryofrenalfunctionandcontributingtomortalitydifference SelectionbiasPatientswhodevelopedearlyAKIbutdidnothaverenalsupportinitiatedearlyandwhoeitherrecoveredrenalfunctionordiedwithouteverreceivingRRT Timingofinitiation Conclusion NoclearcutrecommendationatthismomentDecisionshouldbebasedonindividualbasisAsARFanditsassociatedmetabolicalternationsappearstoincreasetheriskofsevereextrarenalcomplications initiationofRRTshouldbestartedearlyinpatientswithsevere rapidlydevelopingoliguricARF Whattostart IHDvs CRRT PriortothedevelopmentofCRRT IHDandPDweretheonlytwomodalitiesofRRT Withimprovedtechnology CRRThasgainedincreasingpopularity anddevelopedintoawholefamilyofrelatedtherapiestoprovideuninterruptedrenalsupporttocriticallyillpatientsoverperiodofdays WhyCRRT SlowgradualremovaloffluidandsoluteEnhancehemodynamicstabilityPermitbetterfluidandsolutecontrolAllowmoreaggressivenutritionalmanagementEnhancedclearanceofinflammatorymediators particularlyusinghemofiltrationinpatientswithconcomitantsepsis IsCRRTmoresuperior MajorityofstudiescomparingIHDandCRRTarenon randomizedobservationalstudiesorretrospectivecasestudies Confoundingfactorsvariationindiseaseseveritybetweentreatmentgroups unfair randomizationduetointolerancetoIHDsignificantcrossoverbetweenbothgroups Sofarnoconsensusonthisissueyet RaymondVanholderetal JAmSocNephrol12 S40 43 2001 TeehanGSetal JIntensiveCareMed2003 18 130 Mehtaetal ProspectiveRCTinvolving166patientswithARFStudyperiod56monthsEitherCVVH DForIHDBaselinecharacteristics highermales higherAPACHEIIIscores higherprevalenceofliverfailureamongpatientsrandomizedtoCRRTgroupUnivariateintention to treatanalysisrevealedahighermortalityamongpatientsreceivingCRRT 66 vs 48 p 0 02 Mehtaetal Onmultivariateanalysis theRRTmortalityhadnoimpactonallcausemortalitynorrenalrecovery whilebeingreplacedbymoretraditionalriskfactors mainlyAPACHEIIIscoreandnumbersoffailedorgansProblems Unevendistributionofseverityofillnessbetween2groupsAllowpatientstocrossovertherapiesformedicalreasons CommentfromClaudioRoncoClinJAmSocNephrol2 597 600 Patientswereallowedtocrossover makingtruecomparisonimpossiblePatientswithhemodynamicinstability MAP 70mmHg wereexcludedIfpatientsreceivedasufficienttrialofCRRTandsurvived renalrecoverywasdramaticallyincreased 92 3 VS59 4 p 0 01 andthereforeIHDdelayedorimpededrenalrecoveryCRRTdeliveredsuperiorcontrolofuraemia MehtaetalKidneyInt60 1154 1163 2001 VinsonneauetalHemoleafstudyGroup Largest bestpoweredprospectiverandomizedmulticentrestudytocomparetheresultsofCRRTwithIHD360patientsIntentiontotreatNodifferenceinD60survival 32 inIHDvs 33 inCRRT VinsonneauetalLancet368 379 385 2006 VinsonneauetalHemoleafstudyGroup UnexpectedprogressiveandsignificantincreaseinsurvivalratesintheIHDgroupovertime relativerisk0 67 year 95 CI0 56 0 80 p 0 001 LearningcurveforoptimizingIHDtherapyinthestudyenvironmentAnincreaseinthefrequencyofIHDduringthefirst8daysoverthecourseofthestudy withoutcorrespondingincreaseindialyticdoseinCRRTgroupHelbertRondon Berriosetal CurropinionNephrolHypertens16 64 70 2007 Tonellietal AJKD40 875 885 2002 ModalityofRRT conclusion Remainedunanswered Anotherexamplestoillustratethatsoundtechnology devices drugsmaynotnecessarilybeassociatedwithbenefitsorgoodoutcomeE g liberaluseofbloodtransfusion COX2inhibitors SwanGanzcatheter JonathanHimmelfarb Continuousrenalreplacementtherapyinthetreatmentofacuterenalfailure Criticalassessmentisrequired ClinJAmSocNephrol2 385 389 2007 Choiceofdialysers Biocompatibility Bloodmembraneinteractionactivatecellularandhumoralcomponentsofblood leadingtogenerationofseveralbiologicalresponsescomplementactivationcoagulationcascadeactivationmonocytesactivationneutrophildegranulationreleaseofreactiveoxygenspecies Bio incompatiblemembranes e g Cuprophane hemophane MayworsenthecatabolicstateofARFAggravatethepro inflammatorystateofsepsisActivationandsubsequentexhaustionofmononuclearandpolymorphonuclearcellsmaypredisposepatientstobacterialinfectionsHigherobservedmortalityrateduetosepsisDelayrecoveryofARF duetoleucocyteactivationandinfiltrationofrenalparenchyma esp followingischemicreperfusioninjury Membranebiocompatibility WiththecostdifferentialbetweenbioincompatibleandbiocompatibledialysersusedinARFsettlingrapidlydiminishing thereremainsnopersuasivereasontouseunsubstitutedcellulosedialysers HemodialysisinARF Doesthemembranematter ModiGSetal SeminarsinDialysisVol14No5 Sept Oct 2001p318 332 DialyticdoseinARF GFR 100ml min x60 x24x7days 1008L week NoRRTiseverasefficientasnativekidneysThereissomeindicationinESRFpatientsthatuptocertainlevel delivereddoseofRRTisinverselyproportionaltomorbidityandmortality Ureakineticmodeling UKM Dialysisadequacyismeasuredbyureareductionratio URR andKt V K dialyserureaclearancet durationofdialysistreatmentV volumeofdistributionofurea totalbodywater URMinARF ThereisnocurrentguidelinesformeasurementofsoluteclearanceinthesettingofARFApplicationofUKMinARFisnotvalidbecause WhetherureaisasurrogatemarkerforthetoxicmetabolitesinARFisnotestablished esp inthesettingofmultipleorganfailure Hypercatabolicstate negativenitrogenbalanceinARF thereforesteadystateassumptionofkineticmodelsdoesnotapplyInmultipleorganfailure ARFischaracterizedbyinstabilityofhemodynamicparameters increasedpermeabilityofvasculature andtheuseofvasoactivesubstances whichallproducedisequilibriuminureadistribution StefanandEckardt SeminarinDialysisVol19 No6 Nov Dec 2006 p455 464Despitetheselimitations URRremainsthemostwidelyusedmarkersofdialysisadequacyinARFtreatedwithintermittenttherapy Thereisamarkeddiscrepancybetweenprescribedanddelivereddoseofdialysis observedKt VinARFpatientshavebeenshowedtobe30 lowerthanprescribed Jaberetal BloodPurif 2002 20 154 160Schiffletal NEJM2002 346 305 310Earlydiscontinuationofdialysisduetohypotension clottedcircuit catheterdysfunction accessrecirculation LackofsteadystateHighureareboundafterdialysisUncertaintyabouttruetotalbodywater TBW andVolumeofdistributionofureaPresenceorabsenceofresidualrenalfunction Only15 32 oftreatmentsessionsachievedKt V 1 2 TeehanGSetal JIntensiveCareMed2003 18 130 UKMandclinicaloutcomesinARF URR 58 wasassociatedwithsignificantreductioninmortality althoughpatientswithverylowandveryhighseverityscores theirsurvivalrateswerenotalteredwithdialyticdosesmanipulation 78 and0 respectively Paganinietal AmJKidneyDis1996 28 S81 S89 Thisfindingsuggestthepresenceofinterplaybetweenseverityofillnessanddelivereddoseofdialysis andnotnecessarilycause effectrelationship SchiffletalNEJM2002 346 305 310 160patientswithARF assignedinalternateorder to6x weekIHDoralternatedayIHDHighfluxdialysisBaselinecharacteristics APACHEIIIscoresimilarinbothgroupsTreatmenttime bloodflow intradialyticweightlosssimilar SchiffletalNEJM2002 346 305 310 DeliveredKt VhigherindailyIHD 5 8vs 3 0 14daysallcausemortalitysignificantlylowerindailyIHDwhencomparedtoalternatedayIHD 28vs 46 p 0 01 PatientswithclinicaldeteriorationwereallowedtoswitchovertoCRRT arguingfortheneedfora trueefficacy ratherthanintention to treatanalysisNutritionalintakenotreported expectedtobemoreliberalindailyIHD UKMinCRRT DialysersusedinCRRTusuallywithhighUFcoefficientRemoveureaandmiddletolargemolecules 0 3 5Kda includingcytokinesandotherinflammatorymediatorsUsingacomputer basedmodel Clarketaldemonstratedthatina50kgpatient asteadystatebloodureanitrogenof60mg dLbyCRRTwouldrequire4 4sessionsofIHDperweekSimilardegreeofmetaboliccontrolusingIHDwasnotachievableinpatientof 90kg RoncoetalLancet356 26 30 2000 ProspectivelycomparedoutcomesinpatientswithARFreceivingdifferentdosesofCVVHPatientsreceivingUFof35ml kg hrhadsignificantlybetteroutcomesthanthosereceiving20ml kg hr survival57 vs 41 Nostatisticallysignificantdifferenceinsurvivalbetweenpatientsreceiving35and45ml kg hr Howtocomparedialyticdosesindifferentmodalities Artificialorgans30 178 185 Dialyticdose Conclusion UKMinESRFnotvalidatedinARFsettingDialyticdoseestimationinARFwillbedifficultduetodeviationintandV anddelivereddosestendtobelowerthanestimateddosesDialyticdosesmoreeasilyachievedbyCRRTSeverityofillnessanddialyticdosedetermineoutcomes butnotincause effectrelation ACFryetalPostgradMedJ2006 82 106 116 Conclusion ThereisnoconsensusinthemodalityofchoicefordialytictherapyinARF Biocompatibledialysersgivepotentialbenefitofhighchanceofrenalrecoveryinnonoliguricpatients PotentialbenefitofCRRTonclearanceofinflammatorymediatorsinARFwithsepsisThereistendencyofunderdialysis intermo