CRRT的规范化治疗

.,CRRT的规范化治疗,浙江省人民医院孙仁华,.,概述,连续性肾脏替代治疗（continuousrenalreplacementtherapy，CRRT）是指一组体外血液净化的治疗技术，是所有连续、缓慢清除水分和溶质治疗方式的总称。传统CRRT技术每天持续治疗24小时，目前临床上常根据患者病情治疗时间做适当调整。CRRT的治疗目的已不仅仅局限于替代功能受损的肾脏，近来更扩展到常见危重疾病的急救，成为各种危重病救治中最重要的支持措施之一，与机械通气和全胃肠外营养地位同样重要。,血液净化标准操作规程（2010版）,.,CRRT,CRRTisanyextracorprealbloodpurificattiontherapyintendedtosubstituteforimpairedrenalfunctionoveranextendedperiodoftimeandappliedfororaimedatbeingappliedfor24hours/day所谓CRRT也就是指所有每天24小时或接近24小时的缓慢、连续清除水和溶质的治疗方法。,.,历史,1977年，Kramer等首先提出了连续性动静脉血液滤过(continuousarterio-venoushemofiltration，CAVH)1979年，Bambauer-Bishoff提出连续性静脉-静脉血液滤过(CVVH)1980年，Paganini提出缓慢连续性超滤(SCUF)1984年Geronemus提出CAVHD，1987-CVVHD1985年Ronco首次将CAVHDF应用于治疗l例败血症合并MODS患者1992年Grootendorst提出高容量血液滤过(highvolumehemofiltration，HVHF)1998年，Tetra等提出连续性血浆滤过吸附(CPFA),.,主要技术,缓慢连续超滤（slowcontinuousultrafiltration，SCUF）连续性静静脉血液滤过（continuousvenovenoushemofiltration，CVVH）连续性静静脉血液透析滤过（continuousvenovenoushemodiafiltration，CVVHDF）连续性静静脉血液透析（continuousvenovenoushemodialysis，CVVHD）连续性高通量透析（continuoushighfluxdialysis，CHFD）连续性高容量血液滤过（highvolumehemofiltration，HVHF）连续性血浆滤过吸附（continuousplasmafiltrationadsorption，CPFA）,血液净化标准操作规程（2010版）,.,.,.,.,.,.,.,总结,.,急性肾损伤,急性肾损伤(acutekidneyinjury，AKI)是指发生急性肾功能异常，包括从肾功能微小改变到最终肾衰竭整个过程。,.,RIFLECriteriaforAcuteRenalDysfunction,Risk,Injury,Failure,Loss,ESRD,Increasedcreatininex1.5orGFRdecrease25%,EndStageRenalDisease,GFRCriteria*,UrineOutputCriteria,UO.3ml/kg/hx24hrorAnuriax12hrs,UO75%orcreatinine4mg/dl(Acuteriseof0.5mg/dl),HighSensitivity,HighSpecificity,PersistentARF*=completelossofrenalfunction4weeks,Oliguria,.,“AcuteonChronic”Disease,Creatinineisexpressedinmg/dLand(mcmol/L).,.,AKIN分层标准,StageSerumcreatininecriteriaUrineoutputcriteria1Increaseinserumcreatinineofmorethanorequalto0.3mg/dlLessthan0.5ml/kgper(26.4mol/l)orincreasetohourformorethan6hoursmorethanorequalto150%to200%(1.5-to2-fold)frombaseline2IncreaseinserumcreatininetoLessthan0.5ml/kgpermorethan200%to300%hourformorethan12hours(2-to3-fold)frombaseline3IncreaseinserumcreatininetoLessthan0.3ml/kgpermorethan300%(3-fold)fromhourfor24hoursorbaseline(orserumcreatinineofanuriafor12hoursmorethanorequato4.0mg/dl354mol/lwithanacuteincreaseofatleast0.5mg/dl44mol/l),.,适应症,肾脏疾病非肾脏疾病,血液净化标准操作规程（2010版）,.,肾脏疾病,重症急性肾损伤（AKI）伴血流动力学不稳定和需要持续清除过多水或毒性物质，如AKI合并严重电解质紊乱、酸碱代谢失衡、心力衰竭、肺水肿、脑水肿、急性呼吸窘迫综合征（ARDS）、外科术后、严重感染等。慢性肾衰竭（CRF）合并急性肺水肿、尿毒症脑病、心力衰竭、血流动力学不稳定等。,血液净化标准操作规程（2010版）,.,Acuterenalfailure,Asymptomatic,nonoliguric,adequatenutritionpossible,(Non)oliguric,haemodynamicallystable;life-threatheninghyperkalaemia,(Non)oliguric,haemodynamicallyunstable,Highriskofbleeding,Nohighrisk,Expectative,(Increasing)uraemia,IHD#,Unstable,Citrate-CRRT,CRRT,Stable,AlgorithmforthedialytictreatmentofacuterenalfailureaccordingtocircumstancesIHD=intermittenthaemodialysis,CRRT=continuousrenalreplacementtherapy.Delayinitiationofdialytictreatmenttomaximisetheoddsofnativerenalrecovery,#ifnocitrate-protocolforCRRT,heparin-freeIHDmaybeusedasalternativetreatment.,.,非肾脏疾病,非肾脏疾病包括多器官功能障碍综合征（MODS）、脓毒血症或败血症性休克、急性呼吸窘迫综合征（ARDS）、挤压综合征、乳酸酸中毒、急性重症胰腺炎、心肺体外循环手术、慢性心力衰竭、肝性脑病、药物或毒物中毒、严重液体潴留、需要大量补液、电解质和酸碱代谢紊乱、肿瘤溶解综合征、过高热等,血液净化标准操作规程（2010版）,.,禁忌症,CRRT无绝对禁忌证，但存在以下情况时应慎用。无法建立合适的血管通路。严重的凝血功能障碍。严重的活动性出血，特别是颅内出血。,血液净化标准操作规程（2010版）,.,PotentialindicationsforCRRTintheICU,Nonobstructiveoliguria(urineoutput30mmol/l)Hyperkalaemia(K+6.5mmol/lorrapidlyrisingK+)*Suspecteduraemicorganinvolvement(pericarditis/encephalopathy/neuropathy/myopathy),BellomoandRoncoCritCare2000,4:339345,.,PotentialindicationsforCRRTintheICU,Progressiveseveredysnatraemia(Na+160or39.5C)Clinicallysignificantorganoedema(especiallylung)DrugoverdosewithdialyzabletoxinCoagulopathyrequiringlargeamountsofbloodproductsinpatientwithoratriskofpulmonaryoedema/ARDS,AnyoneoftheseindicationsconstitutessufficientgroundsforconsideringtheinitiationofCRRT.TwooftheabovecriteriamakeCRRThighlydesirable.CombineddisorderssuggesttheinitiationofCRRTevenbeforesomeoftheabove-mentionedlimitshavebeenreached.*IHDremovespotassiummoreefficientlythanCRRT.However,ifCRRTisstartedearlyenough,hyperkalaemiaiseasilycontrolled.Forexample,afulminantliverfailurepatientwithadultrespiratorydistresssyndrome(ARDS),aninternationalnormalizedratio3andspontaneousepistaxis.Unlessvolumeisrapidlyremoved,asfreshfrozenplasmaisrapidlygiven,thepatientisverylikelytodeveloppulmonaryoedema.,.,治疗前患者评估,选择合适的治疗对象，以保证CRRT的有效性及安全性。患者是否需要CRRT治疗应由有资质的肾脏专科或ICU医师决定。肾脏专科或ICU医师负责患者的筛选、治疗方案的确定等。,血液净化标准操作规程（2010版）,.,CRRT现状调查,Uchino等报道:前瞻性、观察研究结果，2000.9-2001.12，23个国家、54家ICU、1006例患者的CRRT应用情况。除1例外均采用V-V通路，CVVH占52.8%，33.1%不抗凝，平均剂量为20.4ml/kg/h，仅11.7%35ml/kg/h。,.,CRRT现状调查,常用抗凝剂肝素42.9%、枸橼酸9.9%、甲磺酸萘莫司他6.1%、低分子肝素4.4%。常见并发症为低血压19%，心律失常4.3%，出血3.3%，其中应用低分子肝素者出血为11.4%医院死亡率为63.8%，存活者中有85.5%肾功能恢复,.,Age(years)66(5174)ReasonstostartCRRTGender(male)662/1006(65.8%)Oliguria/anuria703/1002(70.2%)PremorbidrenalfunctionHighurea/creatinine531/1002(53.0%)Normal590/1006(58.6%)Metabolicacidosis437/1002(43.6%)Chronicimpairment283/1006(28.1%)Fluidoverload368/1002(36.7%)Unknown133/1006(13.2%)Hyperkalemia186/1002(18.6%)SAPSII48(3962)Immunomodulation136/1002(13.6%)Predictedmortality(%)41.5(23.071.4)Others70/1002(7.0%)HospitaltoICU(days)1(07)ICUmortality555/1003(55.3%)ICUtostart(days)1.2(0.44.1)Hospitalmortality641/999(64.2%)ContributingfactorstoARFSMR1.38(1.281.50)Sepsis/septicshock504/1003(50.2%)Majorsurgery377/1003(37.6%)Lowcardiacoutput262/1003(26.1%)Hypovolemia201/1003(20.0%)Druginduced176/1003(17.5%)Hepatorenalsyndrome73/1003(7.3%)Obstructiveuropathy20/1003(2.0%)Others114/1003(11.4%),Dataarepresentedasmedianandinterquartileranges(25th75thpercentiles)orpercentages;SAPSII,SimplifiedAcutePhysiologyscore;HospitaltoICU,durationbetweenhospitaladmissionandintensivecareunitadmission;ICUtostart,durationbetweenintensivecareunitadmissionandstudyinclusion;ARF,acuterenalfailure;SMR,standardizedmortalityratio;ICU,intensivecareunit,病人基本情况,IntensiveCareMed(2007)33:15631570,.,CRRTmodeAnticoagulationCVVH531/1006(52.8%)Unfractionatedheparin429/1000(42.9%)CVVHDF342/1006(34.0%)Sodiumcitrate99/1000(9.9%)CVVHD132/1006(13.1%)Nafamostatmesilate61/1000(6.1%)CAVHD1/1006(0.1%)Low-molecular-weight44/1000(4.4%)DilutionsiteforreplacementfluidheparinPredilution509/870(58.5%)Prostacyclin11/1000(1.1%)Postdilution361/870(41.5%)Hirudin9/1000(0.9%)FiltermaterialHeparin-protamine6/1000(0.6%)Polyacrylonitrile457/975(46.9%)Othersb3/1000(0.3%)Polysulfone209/975(21.4%)Combinationc7/1000(0.7%)Polyamide164/975(16.8%)Noanticoagulation331/1000(33.1%)Cellulosetriacetate89/975(9.1%)Polymethyl-methacrylate27/975(2.8%)Polyarylether-sulfone14/975(1.4%)Cellulosediacetate11/975(1.1%)Othersa4/975(0.4%),a3Polyester-polymer-alloy,1ethylene-vinylalcohol;b2danaparoid,1warfarin;c4heparin-citrate,2heparin-prostacyclin,1nafamostatmesilate-low-molecular-weightheparin,CRRT使用情况,IntensiveCareMed(2007)33:15631570,.,Hypotension188/1000(18.8%)Bleeding33/997(3.3%)Indwellingvascularcathetersites13/997(1.3%)Intra-abdominal3/997(0.3%)Gastrointestinal3/997(0.3%)Nostril3/997(0.3%)Sternalwound3/997(0.3%)Othersa8/997(0.8%)Arrhythmia43/1000(4.3%)Atrialfibrillation24/1000(2.4%)Supraventriculartachycardia7/1000(0.7%)Cardiacarrest4/1000(0.4%)Bradycardia3/1000(0.3%)Ventriculartachycardia3/1000(0.3%)Atrialflutter1/1000(0.1%)Ventricularfibrillation1/1000(0.1%),aIntracranial,lowerleg,bonemarrowaspirationsite,oral,andpericardial,并发症,IntensiveCareMed(2007)33:15631570,.,Venkataramanetal,JCritCare,2002,CRRT处方与实际完成的比较,.,何时开始CRRT？,目前没有统一的标准：“时间”、指标等均不统一。Getting等报道：早期开始RRT（BUN42.6mg/dl）比晚期（BUN94.5mg/dl）RRT的生存率高（39%-20%）,IntensiveCareMed1999;25:805-813.,.,AllEarlystarters:Latestarters:pvalue(n=100)BUN60mg/dl(n=41)(n=59)BUNpriortoCRRT(mg/dl)73.2(39.6)42.6(12.9)94.5(28.3)0.0001SerumcreatininepriortoCRRT(mg/dl):nonrhabdomyolysispatients(n=89)a3.26(1.8)2.69(1.6)3.59(4.3)0.025SerumcreatininepriortoCRRT(mg/dl)rhabdomyolysispatientsonly(n=11)5.94(1.2)5.73(1.06)6.50(1.8)0.387CreatinineclearancepriortoCRRT(ml/min)b15.1(19.3)17.4(26.4)13.4(11.6)0.332AlbuminpriortoCRRT(g/dl)c2.612.762.500.049OliguriconCRRTday1(%)46.0056.1039.000.091Heartrate(beats/min)110.0116.8105.312小时；BUN25-30mmol/l,AmJRespirCritCareMedVol162.pp191196,2000,.,治疗模式选择,临床上应根据病情严重程度以及不同病因采取相应的CRRT模式及设定参数。SCUF和CVVH用于清除过多液体为主的治疗；CVVHD用于高分解代谢需要清除大量小分子溶质的患者；CHFD适用于ARF伴高分解代谢者；CVVHDF有利于清除炎症介质，适用于脓毒症患者；CPFA主要用于去除内毒素及炎症介质。,血液净化标准操作规程（2010版）,.,CRRT常用治疗模式比较SCUFCVVHCVVHDCVVHDF血流量（ml/min）50100502005020050200透析液流量（ml/min）10201020清除率（L/24h）123614362040超滤率（ml/min）2582524812中分子清除力血滤器/透析器高通量高通量低通量高通量置换液无需要无需要溶质转运方式无对流弥散对流弥散有效性用于清除液体清除较大分清除小分子清除中小分子物质物质子物质,.,CRRT剂量,慢性肾衰血透的剂量要求是：kt/V1.2CRRT的治疗剂量目前尚无统一意见高容量血液滤过（HVHF）在严重感染、重症胰腺炎（SIRS）中受推崇。,.,100,90,80,70,60,50,40,30,20,10,0,Group1(n=146),(,Uf,=20ml/h/Kg),Group2(n=139),(,Uf,=35ml/h/Kg),Group3(n=140),(,Uf,=45ml/h/Kg),41%,57%,58%,p6mmoLL13(5%)2(7%)0.62pH5gkg1min118(27%)6(18%)0.53Epinephrine15(23%)1(3%)0.02Norepinephrine29(44%)5(15%)0.014Crossovertoalternate18(67%)0(0%)0.002modeofRRT,Jackaetal.CANJANESTH2005/52:3/pp327332,.,A)ICUsurvivalvsRRTmodeSurvivedDiedCRRT29(45%)36(55%)IHD20(71%)8(29%)P=0.02B)HospitalsurvivalvsRRTmodeSurvivedDiedCRRT24(37%)41(63%)IHD14(50%)14(50%)P=0.24C)RenalrecoveryvsRRTmodeRecoveredChronicdialysisCRRT21(87%)3(13%)IHD5(36%)9(63%)P=0.0003,Jackaetal.CANJANESTH2005/52:3/pp327332,结果比较,.,Clarketal,BloodPurif2006,肾功能的恢复,.,Uchinoetal,IntJArtifOrgans2007,肾功能的恢复,.,Belletal,IntensiveCareMed2007,肾功能的恢复,.,Mehtaetal(2002),肾功能的恢复,.,Mannsetal,CritCareMed2003,肾功能的恢复,.,谁管理CRRT？,肾科医务人员ICU医务人员两者合作危重肾脏病专家,.,MehtaRL,LetteriJM:CurrentStatusofRRTforARF.AJN1999;19:377-82,谁管理CRRT？,.,RoncoCetal:ManagementofsevereARFincriticallyillpatients:Intl.Survey345ctrs.NephrologyDialTranspl2001;16:23037,谁管理CRRT？,.,CurrOpinCritCare12:538-43,在ICU中谁管理RRT,.,SomeguidelinestodeliveradequateCRRTontheICU,Startearly:oliguria24hoursoranuria12hours;uraemia25-30mmol/lPrescribeadequatedialysisdose:dailyKt/V1.2;UFvolume35ml/kg/hUse(semi)syntheticbiocompatiblehigh-fluxmembranesUsethevenovenousapproach,preferablyinternaljugularveinMaximiseUFflowrate,beforeaddingslow-dialysis,VanBommel.Renalreplacementtherapyforacuterenalfailureontheintensivecareunit:comingofage?,.,SomeguidelinestodeliveradequateCRRTontheICU,Incaseofsevereliverdysfunction,usebicarbonateasbufferinganionJudicioususeofanticoagulationtoimprovedelivereddialysisdosePrescribe1.2-1.4gprotein/kg/daytoimprovenitrogenbalanceIfthepatientisstabilised,switchtointermittenttreatment,VanBommel.Renalreplacementtherapyforacuterenalfailureontheintensivecareunit:comingofage?,.,指导意见,严重急性肾衰患者应进行肾脏替代治疗何时开始肾脏替代治疗尚无一致意见，但应在严重并发症出现前开始;有限的证据显示:早期开始有利于改善预后无明确的统一的关于选择肾脏替代治疗模式的推荐意见CRRT有利于有肾衰ICU病人的管理,.,指导意见,单纯急性肾功能