血液净化原理,模式及治疗的选择

TipsforimprovingfilterlifeAquariusSystemCopyright©2015NIKKISOCo.,LTD.Allrightsreserved.PM-0063-11/2015-1

当前1页，总共66页。肾脏替代治疗“的内容肾脏替代治疗的基本内容滤器的选择抗凝剂的应用当前2页，总共66页。

3CRRT命名的发展CRRT：Continuousrenalreplacementtherapy（连续肾脏替代治疗）ICBP:Intensivecarebloodpurification（重症血液净化）CBP：ContinuousBloodpurification（连续血液净化）MOST：MultiOrganSupportTherapy（多脏器支持疗法）当前3页，总共66页。

4CRRT的特点和优越性

CRRT是缓慢、连续排除水分，模拟尿的排泄方式。更符合生理状态，能较好地维护血流动力学稳定；容量波动小；溶质清除率高；有利于营养改善及能清除细胞因子，从而改善危重ARF患者的预后，更好的血液动力学稳定性更好的溶液控制能力和清除多余水分累积的更好溶质清除性维持尿排泄并保存残余肾功能清除炎症介质改善营养支持当前4页，总共66页。

5

CRRT的分类SCUF-缓慢连续超滤CAVH-连续动静脉血液滤过CVVH-连续静静脉血液滤过HVHF－高容量血液滤过CAVHD-连续动静脉血液透析CVVHD-连续静静脉血液透析CVVHFD－连续静静脉高通量透析CAVHDF-连续动静静脉血液透析滤过CVVHDF-连续静静脉血液透析滤过MPS-血浆置换HP-血液灌流和免疫吸附CRRT以一种更符合机体生理特性的方式，连续地清除机体多余的水分和毒素，调节酸碱和电解质的平衡，来有效地维持机体内环境的稳定。不单用于急性肾衰，还是救治许多危重病症的有力辅助手段。当前5页，总共66页。

6原理与机制弥散对流吸附500500050000当前6页，总共66页。SoluteClassesbyMolecularWeightDaltons•

InflammatoryMediators(1,200-50,000)“small”“middle”“large”当前7页，总共66页。Jean-MichelLannoyNikkisoABPDirector8炎症介质的特征介质分子量C3a2500C5a2800TNF-a17500x3C5a2800IL-62125000IL-1Ra14000IL-89000LPS100000FactorD2300023000当前8页，总共66页。Jean-MichelLannoyNikkisoABPDirector9炎症介质的特征介质蛋白结合分子量C3ano2500C5ano2800TNF-a部分17500x3STNRFIyes55000STNRFIIyes75000IL-621yes25000IL-1Rano14000IL-lano89000PAF部分450FactorDyes23000当前9页，总共66页。3/10/202310PSHF系列滤器筛选系数/高截留分子量当前10页，总共66页。如何选择血滤器？Jean-MichelLannoyNikkisoABPDirector11当前11页，总共66页。MolecularWeights（分子的重量或分子量的大小）12Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.Ashleyetall.TheRenalDrugHandbook,2ndEd.2004,MedicalPress,Abingdon,UK.ISBN:1857758730当前12页，总共66页。NewfunctionalmembranewithdefinedlargerporesizeHCOmembrane当前13页，总共66页。<0,01µm<0,02µm~0,09µm~0,30µm:porediameterhighfluxhighcut-off*proteinseparationmembraneplasmaseparationmembraneVariationofmembraneporesizeElectronmicrographsofinnermembranesurface当前14页，总共66页。sievingcoefficient100100010000100000100000000.20.40.60.81Molecularweight[D]ClassicalFilter30kDhumankidneyhighcut-offHighCut-OffHemofilter当前15页，总共66页。SievingCoefficientAsievingcoefficientisthemeasureofhoweasilyasubstancepassesfromthebloodcompartmenttothedialysatecompartmentinahaemofilter.Thus,asievingcoefficientof1.0meansthesoluteis100%filterable;i.e.inahaemofilter,thesolutewillequilibrateonbothsidesofthemembrane.So…thereturningbloodandtheeffluentbothhavethesameconcentration(50:50).Anexampleispotassium(sievingcoefficientis1.0)Asievingcoefficientof0meansthesolutedoesnotcrossthemembrane,eg.albumin.Ofcourse,thisalldependsonthemembrane,andsievingcoefficientswillvarydependingontheporesize.DEFINITION:Thecut-offpointofasoluteforanymembraneisasievingcoefficientof0.1.Thismeansthat10%ofthemoleculeswillpassand90%willnotpass.16Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前16页，总共66页。MolecularWeight[Da]StandardHighFluxHighCut-OffHF,UF=1L/h,t=2hMedian,25th-75thpercentiles)ICM(2002)28:651-655HCOMembranewithincreasedpermeabilityforinflammatorymediatorsmembranecharacteristics

当前17页，总共66页。Molecularweight18Ashleyetall.TheRenalDrugHandbook,2ndEd.2004,MedicalPress,Abingdon,UK.ISBN:1857758730Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.HF1200HaemofilterCut-Off55000daltons当前18页，总共66页。ComparisonofInterleukin-6RemovalPropertiesamongHemofiltersConsistingofVaryingMembraneMaterialsandSurfaceAreas3/10/202319RecentStudiesinMembrane当前19页，总共66页。20全身抗凝

局部抗凝

无肝素抗凝肝素低分子肝素钙鱼精蛋白枸橼酸抗凝的选择Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前20页，总共66页。积极主动预防管路的凝血

利用重新预冲和循环模式清除管路及滤器中的气泡

仔细观察预冲后管路的通畅.保持静脉壶的血液水平在二分之一以上，

减少气血接触防止静脉小壶的凝血，静脉

小壶的凝血影响了血液的流速压力降21Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前21页，总共66页。预防滤器内的凝血(FiltrationRatio%)保持超滤比率在25%一下.超滤比率是衡量滤器中

血液浓度(血流速率与滤出是百分比）.是多少血夜

进入滤器和多少液体排除的比较。

目标血流速度的目的制定达到低的超滤比率，

从而达到更长的滤器使用寿命.高的血流速度可以达到低的超滤比率

如果临床需求允许可以提高血流速10—15%当连接病人时，可以延长治疗直到血流速度达到要求尽可能的在病人开始治疗时防止血液的浓缩22Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前22页，总共66页。预防滤器内的凝血(Recirculation)

重复循环模式：连接病人之前重复循环20-40/min，

重复循环可以侵泡滤器的纤维，同时排空纤维中的

空气.滤器的纤维经过侵泡更加的饱满，改善血流通过

纤维的流量，排除极小的气泡防止早期的凝血.

一个循环时间在20–20/minutes.滤器和管路基本可以

72小时使用,

但这包括重复使用的时间.23Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前23页，总共66页。FiltrationFraction（滤过分数）FiltrationFraction滤过分数是

总液体通过

滤器的量与超滤量的相比

滤过分数通常是尽可能的低，理想是25%

FiltrationFraction滤过分数是

不会受到前

稀释泵的影响FiltrationFraction滤过分数是会受到血流速

的影响.

24Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前24页，总共66页。超滤比率FiltrationRatio25Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.FiltrationRatio是表示滤器中血液浓度增加.理想的超滤比率在低于

25%.FiltrationRatio是受到前稀释泵的影响.FiltrationRatio是受到血流速的影响.当前25页，总共66页。FiltrationRatioandbloodpumpspeed

Postdilution(l/h)BloodPumpSpeed(mls/min)60(mins)=FiltrationRatio /1000

3l/hExchange

3

1

100mls/minx60mins=6=2=50%FiltrationRatio/1000

3l/hExchange

3

1

200mls/minx60mins=12=4=25%FiltrationRatio

3l/hrExchange

3

1

300mls/minx60mins=18=6=17%FiltrationRatio

26Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前26页，总共66页。肝素是如何工作的?Heparin肝素抑制导致血液凝固和纤维蛋白凝块形成的反应.肝素在抗凝系统中是多部位的作用.小剂量的肝素，与抗凝血酶III结合，

可以抑制凝血酶块的形成通过消除

FactorX因子.减少了凝血素转化成凝血酶治疗剂量的肝素有利于血滤器的寿命.5Roncoetal.Effectsofdifferentdosesincontinuousveno-venoushaemofiltrationonoutcomesofacuterenalfailure:aprospectiverandomisedtrial.Lancet.2000Jul1;356(9223):26-30Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前27页，总共66页。肝素;优势和劣势优势:

容易管理和监控

ICU非常熟悉肝素抗凝.

便宜.

短的半衰期.

肝素可以中和.缺点:

增加出血的风险.

血小板减少.

增加肝素的剂量.

抗凝血酶元水平下降会影响肝素的作用.

Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前28页，总共66页。枸橼酸是如何工作的?枸橼酸螯合了血循中的钙.抑制了凝血ACD-A(CitrateSolution)WhatcitratebindstocalciumwhichinhibitscoagulationCopyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前29页，总共66页。合适的枸橼酸剂量30离子

Calcium50%1.1–1.3

mmol/l蛋白

Calcium40%0.95–1.2

mmol/l复合

Calcium10%0.1mmol/l图表显示钙在血浆中的分布情况.枸橼酸剂量考虑是

TotalCalcium(typically2.2-2.6mmol/l)andTotalMagnesium(typically1.1–1.4mmol/l).影响到选择枸橼酸的量

Citratedosingbetween3.3–4.0mmol/l.Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前30页，总共66页。WhatdoesthebodydowithCitrate?Citrateisconvertedintocitricacid.转化成枸橼酸Yielding/resultinginthereleaseofbicarbonate.释放碳酸盐AlsometabolisedintheKrebscycleintheliver,skeletalmuscleandrenalcortex.（肝脏，肌肉，肾皮质）Ormetabolisedintoglucose代谢到糖.Excreted分泌，排泄.Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前31页，总共66页。Therapymonitoring32Theselectionandadjustmentoftherapyparameters,replacementfluidsandanticoagulantfluidsremainsaprescriptionatthephysician'sdiscretion.Achangeinanindividualprescriptionwillrequirephysicianrevieworbeclearlydefinedinalocallyapproveddocument.Tomonitorandadjustthetherapy,thefollowingtypicalparametersmaybeconsideredintheindividualizedprescriber’slocalprotocol:IonisedCalcium(afterhemofilter)typically0.25-0.35mmol/lIonisedCalcium(frompatient)typically1.05-1.3mmol/lTotalCitrate(frompatient)typicallylessthan2.5mmol/lCalciumRatio(acomparisonofCalciumdistribution)typicallylessthan2.3Acid/basemonitoringElectrolytesmonitoringFluidbalancemonitoringCopyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前32页，总共66页。AquariusRegionalCitrateAnticoagulationProtocolJohnRProwleMDFRCPFFICMAdultCriticalCareUnitRoyalLondonHospital当前33页，总共66页。EligibilityforRCARequiringRRTwithintheICU(eitherneworon-goingtreatment)forconventionalRenalindicationsConsideredbythetreatingPhysiciantohaveacontraindicationtoheparinanticoagulationorunabletoachieveadequatefilterlifespan(>12h)usingheparinAppropriatelytrainednursingstaffavailable当前34页，总共66页。Contra-indicationstoRCAinpilotRequirementforsystemicanticoagulant(otherthanprophylaxis)ChronicLiverDisease-ChildsBorCAcuteLiverInjurywithINR>2orLactate>4µmol/LPost-hepaticresectionSevereshock:Noradrenaline>0.5mcg/kg/minand/orLactate>4µmol/LArterialBloodIonizedCalcium<0.8µmol/LatcommencementofRCAArterialBloodpH>7.5orHCO3-

>40mmol/LatcommencementofRCASerumSodium<120or>160atcommencementofRCAUncontrolledhyperglycaemia>6U/hInsulinIBW>90kg当前35页，总共66页。35ml/kg/hCVVHRCAProtocolAllpatientswillstartat35ml/kg/hunlessdirectedbyphysicianDoseincludescitratevolumepre-filterFiltrationRatiois20%Pre-filtercitrateconcentrationwillbe~2.8mmol/LIBWkgPost

–dilutionmL/hBloodPumpmL/minACD-A

(Citrate)mL/h<50140012018050-59180015023060-69210018027070-792400200300>802700230350Protocol1当前36页，总共66页。CalciumReplacementAccusolreplacementsolutioncontains1.75mmol/LCalciumwhichwillprovidemostoralloftheCalciumreplacementA10mmol/LCalciumChloridesolutionwillbeusedforadditionalCalciumreplacementifrequired:1x10mlampuleofCalciumChloride(10mmol)in990mlNormalSalinegivenviaintegratedCalciumPumponAquarius-CitratedeviceonlyInfusionrate0-175ml/h当前37页，总共66页。InitialCalciumRateThencheckarterialCaiin1hSystemiciCaInitialrateofCaClsolution<0.8DoNOTcommenceRCAMedicalteamtoreview&correctCalcium0.8-0.975mL/h(0.75mmol/h)0.9-1.050mL/h(0.5mmol/h)>1.00mL/h(0mmol/h)Usethistable

onlywhenfirststartingRCA当前38页，总共66页。AdjustingCalciumInfusion[iCa]CaClinfusionadjustment(MAXIMUMRATE=175mL/hr):Recheck<0.8Doctortogive5ml,10%CaCl(3.4mmol)‘minijet’byslowIVbolusviaacentrallineimmediatelyIfCaClalreadyrunningthenincreaseinfusionby50ml/hIfstartingCaClthenstartat100ml/hIfCaClinfusionalreadyat175ml/hceaseRCA

&informICUConsultant1h0.8-0.89IfCaClalreadyrunningthenincreaseinfusionby25ml/hIfstartingCaClthenstartat75ml/hIfCaClinfusionalreadyat175ml/hceaseRCA&informICUConsultant3h0.9-1.3Nochange3h*>1.3DecreaseCaClinfusionby25ml/hIfCaClinfusionoffthenchecksystemic[iCa]in3hoursInformDoctorif[iCa]risesto>1.53h*Likelytochangetocheckin6hinfinalprotocol当前39页，总共66页。MonitoringBaselineABGfor

iCa2+&HCO3-LabBloodswithin12hforU&EMg2+TotalCa2+Aftertheonehour:

ABGforiCa2+&HCO3-Thereafterevery3h*:ABGforiCa2+&HCO3-monitoring(unlessearliercheckrequiredafteradjustmentofCalciuminfusion)Aroundevery12hours:LabBloods:U&E;TotalCa2+;Mg2+

(AimMg>1mmol/L)PostFilteriCa2+(Takefromreturn-linesampleport)RecordallResultsonRCAPro-forma*Likelytochangetocheckin6hinfinalprotocol当前40页，总共66页。Start35ml/kg/hCVVHIfpH>7.5orHCO3->40Reduceto25ml/kg/hIfpH>7.5orHCO3->40Use25ml/kg/hwith25%FRIfpH>7.5orHCO3->40StopRCAMetabolicAlkalosisMonitorpHandBicarbonate3hly**Likelytochangetocheckin6hinfinalprotocol当前41页，总共66页。IBWkgPost

–dilutionmL/hBloodPumpmL/minACD-A

(Citrate)mL/h<50110010015050-59130011017060-69150013020070-791700140210>801900160240IBWkgPost

–dilutionmL/hBloodPumpmL/minACD-A

(Citrate)mL/h<50Reachedminimumbloodflowrate–DISCONTINUERCA50-59Reachedminimumbloodflowrate–DISCONTINUERCA60-69150010015070-791700120180>801900130200Step2:ifpH>7.5orHCO3->40mmol/LonProtocol2changesettingstoProtocol3(25ml/kg/hwithincreasedfiltrationratio)belowandmonitorevery3h*Step3:ifstillpH<7.5orHCO3->40mmol/LDISCONTINUERCAStep1:

ifpH>7.5orHCO3->40mmol/LonProtocol1

ChangethesettingstoProtocol2(25ml/kg/h)belowandcontinuetomonitorevery3h*.(Protocol2mayalsobeselectedfordosereduction)Protocol2Protocol3*Likelytochangetocheckin6hinfinalprotocol当前42页，总共66页。Howitworks…当前43页，总共66页。Jean-MichelLannoyNikkisoABPDirector44当前44页，总共66页。THANKS!3/10/202345当前45页，总共66页。IndicationsforCitrateAnticoagulationRequiringRRTwithintheICU(eitherneworon-goingtreatment)forconventionalRenalindicationsConsideredbythetreatingPhysiciantohaveacontraindicationtoheparinanticoagulationAppropriatelytrainednursingstaffavailable8PalssonR,NilesJL,RegionalcitrateanticoagulationincontinuousvenovenoushemofiltrationincriticallyillpatientswithahighriskofbleedingKidneyInt1999,55:1991-1997.9FlaniganMetal.Reducingthehemorrhagiccomplicationsofhemodialysis:Acontrolledcomparisonoflow-doseheparinandcitrateanticoagulation.AmJKidneyDis1987;2:147-153Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前46页，总共66页。ContraindicationsChronicLiverDisease-ChildsBorCAcuteLiverInjurywithINR>2orLactate>4µmol/LPost-hepaticresectionSevereshock:Noradrenaline>0.5mcg/kg/minand/orLactate>4µmol/LArterialBloodIonizedCalcium<0.8µmol/LatcommencementofRCAArterialBloodpH>7.5orHCO3-

>40mmol/LatcommencementofRCAReductionofrequirementsforsystemicanticoagulant(otherthanprophylaxis)SerumSodium<120or>160atcommencementofRCAUncontrolledhyperglycaemia>6U/hInsulinIBW>90kgCitrateintoleranceClinicalsituationwherecitratemetabolismbecomesuncertain.Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.10Prowleetal.ServiceDevelopmentPlanandProtocolforRegionalCitrateAnticoagulation,TheRoyalLondonHospital当前47页，总共66页。TherapymonitoringIonisedCalcium:

Ionizedcalciumisameasureoffreecalcium.

Afterhemofiltertypically0.25-0.35mmol/l

Frompatienttypically1.05-1.3mmol/lTotalCalcium:

Totalcalciumincludesbothprotein-boundandfreecalcium.

TotalCalcium(frompatient)typicallylessthan2.5mmol/lAcid/basemonitoring:SystemicpHwillbemonitored3-6hrly.Glucosemonitoring:Bloodglucosemonitoredforhyperglycaemia3-6hrlyElectrolytemonitoring:Levelstobemonitored3-6hrly.Fluidbalancemonitoring.Anyotherclinicalsigns?Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前48页，总共66页。OptimizeVascularAccessConsiderusingahighflowsiliconevascularaccesscatheterthatdoesnothave“kinkmemory”,andwithanappropriatelengthforthechosensite.AvoidattachingtheAquariustoacatheterwithpoorflow.Forexample,beingabletowithdraw20mlofbloodin6secondsor10mlofbloodin3secondswithouthesitancyorinterruptionmayhelpacatheterassessment.Considerrotatingthehubofthecatheter90°sothattheholesontheaccesslumenarefacingtheflowofblood,notagainstthevesselwall(youmayneedtomomentarilystopthebloodpumptodothis).Considerthepatientsintravascularvolume.Eventhoughthepatientmaybefluidoverloaded,iftheirintravascularspaceisdehydrated,theremaybepoorflowthroughthecatheterwhichwillencourageclotting.49Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前49页，总共66页。OptimizeAnticoagulationHighreturnpressureisonesignofunderanti-coagulation.Thebloodpumpwantstopushthebloodthroughthereturnchamberwherepartiallyformedbloodclotsmayincreaseinsize,makingitdifficultforthebloodtosqueezethrough.Aroutineofregularobservation,followedbyacheckofthepatientclotting,andadjustmentofanticoagulantwhereindicated,maypreventearlyreturnchamberclotting.Considerincreasingtheproportionofpre-dilutionifanticoagulation

adjustmentisnotindicated.Forexample:alteringthepre-dilutionto90%andreducingpost-dilutionto10%maythinthebloodpassingthroughthefilterandreducetheeffectsofhaemoconcentration.Againinlifespanmaybeoffsetbyasmalllossinclearance,easilyadjustedbyusingtheRenalDosedisplay.50Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前50页，总共66页。Theeffectofbloodpumpspeed51Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.Filtrateremovedisapercentageoftotalflowthroughthefilterfibres.Whyisthetotalbloodflowimportant?Withafasterbloodpumpspeed,thetotalflowisincreasedandeffectsofhaemoconcentrationarereduced.Increasingbloodflowgivesareducedfiltrationratiowhichmayslowfiltercloggingandextendfilterlifespan.当前51页，总共66页。TheeffectofPre-dilution52Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.Filtrateremovedisapercentageoftotalflowthroughthefilterfibres.Theproportionofpredilutionflowmaybeadjustedtooptimisetreatment.Withagreaterproportionofpredilution,thefiltrationfractionandeffectsofhaemoconcentrationarereduced.Animprovedfiltrationfractionmayslowfiltercloggingandextendfilterlifespan.当前52页，总共66页。Considerations53Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.Diameter,lengthandtypesofcatheters(II)Type:MaterialfeaturesSiliconeelastomercathetershavelowerthrombogenicity

andbetterflexibility.BiocompatibleandkinkresistanceConformtovesselanatomy,thereforereduceriskoftraumaDiameterandbloodflow:11French:250-300ml/minBloodFlow13.5French:450-500ml/minBloodFlowRecirculation-upto20%Especiallyiffemoralaccessislessthan20cmAvoidreverseAVconnection当前53页，总共66页。PatientPreparation54Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.PatientbodystatusCoagulationandIntravascularfillingMobilityinfluencesPresenceofothercentrallinesInfluencesoncatheterchoiceClinicianchoiceAvailabilityofultrasoundguidanceAssessmentofcatheterpatencyConnectiontechniquesSpecialcircumstances当前54页，总共66页。CatheterCharacteristics

55Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.

Easeofinsertion:toavoidvesseltraumaGoodflowcharacteristics:tooptimisebloodflowKinkresistant:toavoidaccesspressureproblemsBiocompatible:toreducecomplicationrisksAmenabilitytoguidewirechange:tooptimisetherapy当前55页，总共66页。Side-by-SidePolyurethaneCatheters56Copyright©2015NIKKISOCo.,LTD.Allrightsreserved.当前56页，总共66页。CoaxialPolyurethaneCatheter