急性肺动脉栓塞及进展心内科 .ppt

,急性肺栓塞诊疗指南及进展GuidelinesandProgressontheDiagnosisandManagementofAcutePulmonaryEmbolism,SouthwestHospital,何国祥Prof.GuoxiangHE第三军医大学西南医院重庆市介入心脏病学研究所SouthwestHospitalTheThirdMilitaryMedicalUniversityChongqingInstituteofInterventionalCardiology,SouthwestHospital,Updatein2019,中国急性肺血栓栓塞症诊断治疗专家共识,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,1、背景2、临床评估3、定量评估4、治疗抗凝溶拴手术导管治疗5、妊娠PE6、非血栓PE,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,1、背景2、临床评估3、定量评估4、治疗抗凝溶拴手术导管治疗5、妊娠PE6、非血栓PE,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG1.Venousthromboembolism(VTE)/100,000population/yearfrom1990through2019.(DatafromSteinetal.3-5),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG2.Deepvenousthrombosis(DVT)/100,000population/yearshownaccordingtoagefortheyear2019.6,7(Reprintedwithpermission.10),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG3.Pulmonaryembolism(PE)/100,000population/yearshownaccordingtoagefortheyear2019.(DatafromSteinetal.5,6)(Reprintedwithpermission.10),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG12.EstimatedcasefatalityratesforPEaccordingtodecadesofage.(Reprintedwithpermission.23),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG4.PEandDVTinchildren.(DatafromSteinetal.7),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Majorriskfactorsforvenousthrombosis,MajorsurgeryOrthopaedicsurgerytolowerlimb/lowerlimbtraumaHistoryofpreviousvenousthrombosisCancerPregnancy/puerperiumReducedmobilitymajorillnesswithprolongedbedrestAge70yearsThrombophilias:antithrombindeficiencyproteinCdeficiencyproteinSdeficiencyantiphospholipidantibodies,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,1、背景2、临床评估3、定量评估4、治疗抗凝溶拴手术导管治疗5、妊娠PE6、非血栓PE,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TABLE5.Electrocardiographicmanifestations:patientswithoutpriorcardiacorpulmonarydisease,DatafromSteinetal.29,57Reprintedwithpermission.10Somepatientshadmorethan1abnormality.,CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TABLE6.Plainchestradiographinpatientswithacutepulmonaryembolismandnopriorcardiopulmonarydisease,DataarefromSteinetal.29,63Reprintedwithpermission.10aAmongpatientswithapleuraleffusion,86%hadonlybluntingofthecostophrenicangle.Nonehadapleuraleffusionthatoccupiedmorethanonethirdofahemithorax.bProminentcentralpulmonaryarteryanddecreasedpulmonaryvascularity.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,肺实质异常,肺不张/萎陷,肺实变,胸水,SouthwestHospital,FIGURE2.V/QSPECTforthedetectionofpulmonaryembolism,V/QSPECTthermalimagingcoronalposteriorsectionsinafemalepatientshowmultiplelargepulmonary-ventilatoryareasofmismatchthatindicatepulmonaryembolithatinvolvetheupperandlowerlobesoftherightlung(whitearrows).V/QSPECT,ventilationandperfusionsinglephotonemissioncomputedtomography.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG19.RelativeuseofdiagnosticimagingtestsinpatientshospitalizedwithPEfrom1979through2019.V/Q,ventilation/perfusion;ANGIOS,pulmonaryangiograms.(Reprintedwithpermission.10),CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG20.CTpulmonaryangiogramshowingPEintherightpulmonaryartery.,CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,FIG21.CTvenousphaseimageshowingrightpoplitealveinthrombosis(arrow).,CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Threeimagesfromasinglecomputedtomographypulmonaryangiography(CTPA)studyperformedwithahighclinicalsuspicionofpulmonaryembolism(PE).Image1demonstratesalargePEintheproximalrightpulmonaryartery.Image2showsasignificantconcurrentpneumothorax.Image3demonstratesanRV/LVratio1signifyingsignificantrightventricular(RV)dysfunction.TogethertheseimagesshowthehighutilityofCTPAindiagnosis/exclusionofPE,diagnosis/exclusionofdifferentialdiagnoses,andinriskstratifyingapatientsoastoguidetherapy.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,CausesofaraisedD-dimervenousthromboembolicdiseaseincreasingagecancerinfectionhaematomapostsurgeryinflammationpregnancyperipheralvasculardiseaseliverdisease,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TheThrombo-EmbolismLactateOutcomeStudy血栓-栓塞乳酸盐转归研究PrognosticValueofPlasmaLactateLevelsAmongPatientsWithAcutePulmonaryEmbolism血浆乳酸盐水平在PE患者中的预后价值,AnnEmergMed.2019;xx:xxx,Table2.Descriptionof30-dayoutcomeofpatientsinvestigated(n=270).*,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Figure3.All-causedeathandcompositeendpointincidenceinpatientswithincreasingvaluesofplasmalactatelevel.,乳酸盐水平与全因死亡和复合终点,AnnEmergMed.2019;xx:xxx,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Figure4.Coxproportionalhazardanalysisoftherelationshipbetweenplasmalactatelevelgreaterthanorequalto2mmol/Landoutcomein270patientswithacutepulmonaryembolism.,AnnEmergMed.2019;xx:xxx,全因死亡,复合终点,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Figure5.Receiveroperatingcharacteristiccurveanalysisofplasmalactatelevel,troponinIlevel,andsPESIvaluesin270patientswithacutepulmonaryembolism.,AnnEmergMed.2019;xx:xxx,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,ElevatedHeart-TypeFattyAcid-BindingProteinLevelsonAdmissionPredictanAdverseOutcomeinNormotensivePatientsWithAcutePulmonaryEmbolism心肌脂肪酸结合蛋白水平升高预测血压正常的APE病人不良转归,(JAmCollCardiol2019;55:21507),Figure1PrognosticSensitivityandSpecificityofH-FABP,cTnT,andNT-proBNP,Receiveroperatingcharacteristiccurvesforheart-typefattyacid-bindingprotein(H-FABP),cardiactroponinT(cTnT),andN-terminalpro-brainnatriureticpeptide(NT-proBNP)levelsonadmissionwithregardtoacomplicated30-dayoutcome.AUCareaunderthecurve.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Figure2CombinationofH-FABPWithClinicalParametersThenumberofpatientswithcomplicationsandtheoverallnumberofpatientsaregiven,alongwithpercentages,foreachcolumn.H-FABPheart-typefattyacidbindingprotein;HRheartrate;RVrightventricular.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Figure3ProbabilityofLong-TermSurvivalinPatientsWithorWithoutElevationofH-FABP,cTnT,andNT-proBNPBiomarkerlevelsweredichotomized,andelevatedconcentrationsweredefinedasthose6ng/mlforH-FABP,0.04ng/mlforcTnT,and1,000pg/mlforNT-proBNP.Redlineselevatedvalues;bluelinesnormalvalues;pvalueswerecalculatedbythelog-ranktest.AbbreviationsasinFigure1.,JACC2019;55(19):21507,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Fig.1.Pathophysiologyofrightventriculardysfunctionduringacutepulmonaryembolism.RV:Rightventricule;LV:Leftventricle;TXA2:Thromboxane-A2;ET:Endothelin;PGF2a:ProstaglandinF2a;PGI2:Prostacyclin.Greyarrowindicatesthatallconstitutedaviciouscycle.Blackarrowindicatespathophysiologychange.,JMedCollPLA2019；25：235-246,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Table2EchocardiographicriskassessmentinPE1.DiagnosticcriteriaforRVdysfunctionRV功能不全的标准A.RVwallhypokinesis-Moderateorsevere-McConnellssignregionalRVhypokinesisinwhichtheapexissparedB.RVdilatation-End-diastolicdiameter30mminparastemalview-RVlargerthanLVinsobcostalorapicalview-Increasedtricuspidvelocity26m/sec-ParadoxicalRVseptalsystolicmotionC.Pulmonaryarteryhypertension-Pulmonaryarterysystolicpressure30mmHg-DilatedIVCwithlackofrespiratorycollapse2.OtherfactorsassociatedwithincreasedmortalityA.PatentforamenovaleB.Free-floatingnight-heatthrombus,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Fig.1PhysicianassessmentofpatientswithPE.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,PE的临床评估,SouthwestHospital,1、背景2、临床评估3、定量评估4、治疗抗凝溶拴手术导管治疗5、妊娠PE6、非血栓PE,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Assessmentofclinicalprobability,RevisedGenevaScorePointsAge60years1PreviousVTE3Surgery/fracturelowerlimbinlastmonth2Activemalignancy2Unilaterallowerlimbpain3Haemoptysis2Heartrate75943Heartrate955Painonlowerlimbdeepvenouspalpationandunilateraloedema4ClinicalprobabilityTotalpointsLow03Intermediate410High10,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,ModifiedWellsscore6PointsSymptomsofaDVT3Noalternativediagnosis3Heartrate1001.5Immobilizationorsurgeryinthepreviousmonth1.5PreviousVTE1.5Malignancy1.5Haemoptysis1.5Score4orless,PEunlikely,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TABLE12.PositivepredictivevaluesofCTAandCTA/CTVinrelationtopriorclinicalassessment,OnlypatientswithareferencetestdiagnosisbyV/QscanorconventionalpulmonaryDSAwereincluded.Abbreviations:CTA,computedtomographicpulmonaryangiography;CTV,venousphasevenogram.Reprintedwithpermission.14,CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TABLE13.NegativepredictivevaluesofCTAandCTA/CTVinrelationtopriorclinicalassessment,OnlypatientswithareferencetestdiagnosisbyV/QscanorconventionalpulmonaryDSAwereincluded.Abbreviations:CTA,computedtomographicpulmonaryangiography;CTV,venousphasevenogram.Reprintedwithpermission.14,CurrProblCardiol2019;35:314-376,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,BTSscorePointsIsaPEareasonablediagnosis?1PE的诊断合理?Isanalternativediagnosislesslikely?1可能性小?Isamajorriskfactorpresent?1存在主要危险因素?1point,lowclinicalprobability;2points,intermediateclinicalprobability;3points,highclinicalprobability.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,1、背景2、临床评估3、定量评估4、治疗抗凝溶拴手术导管治疗5、妊娠PE6、非血栓PE,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,AcutePulmonaryArteryEmbolism,SouthwestHospital,Fig.3PathophysiologyofRVdysfunctionanddeathinPE.,SouthwestHospital,循环的维持：IncreasingMAP(i.e.fillingandpressorsupport)ReducingRVPm(i.e.reducingPAPs/pulmonaryvascular)resistance(selectivepulmonaryvasodilators(e.g.nitricoxideorinhaledprostacyclin)thoughthesemayresultinsystemichypotension增加MAP，降低RVPm，尽管可以导致体循环低血压Noradrenalinecancounteracttheseconcernstoadegreeandisalsothepreferredinotropeforitsconcomitantbeneficialalphaandbeta-adrenergiceffectsonMAPandcardiacoutputrespectively去甲肾上腺素：增加MAP和COInotropesthathavesystemicvasodilatoryeffects(suchasmilrinoneordobutamine)whichmayincreasecardiacoutputwithoutincreasingMAPandthereforenotsignificantlyimproveRVCPP具有体循环血管扩张作用的药物（米力农、多巴酚丁胺）可增加CO，但不增加MAP，而不显著改善RVCPPRightventricularcoronaryperfusionpressure(RVCPP=MAP-RVPm),ANAESTHESIAANDINTENSIVECAREMEDICINE2019；11:12,AcutePulmonaryArteryEmbolism,SouthwestHospital,Anticoagulation抗凝：有充分理由支持诊断PE：开始全剂量的LMUH治疗由影像学证实和确诊PE：停LMUH改为warfarin（INR=2-3，目标=2.5）为门诊病人安排监测INR,AcutePulmonaryArteryEmbolism,SouthwestHospital,Suggesteddosing,heparintherapy,ANAESTHESIAANDINTENSIVECAREMEDICINE2019；11:12,AcutePulmonaryArteryEmbolism,SouthwestHospital,Howlongtotreat?,根据PE的原因而异通常6W-3M可能足够病因持续存在:抗凝持续原发/先天性PE,一旦停止治疗,复发率410%/年，4年以上远期事件率20%因此,I级事件后应终身抗凝治疗,但需要权衡治疗的获益与风险严重出血(颅内出血；腹膜后出血；Hb降低需要输血者）：75岁1%/年75岁5%/年决策治疗疗程前与病人/家属讨论利弊是明智/必要的,AcutePulmonaryArteryEmbolism,SouthwestHospital,Fig.2.Percentageandsizeofresidualpulmonarythrombi.Greater,similarandsmallerocclusionmeanbigger,sameandlessersizeofpulmonarythrombirespectivelyasseeninsecondcomputedtomography.,EurJIntMed2019；23：379383,EurJIntMed2019；23：379383,Residualpulmonarythromboemboliafteracutepulmonaryembolism继发于肺栓塞的残余肺血栓,AcutePulmonaryArteryEmbolism,SouthwestHospital,EurJIntMed2019；23：379383,Residualpulmonarythromboemboliafteracutepulmonaryembolism继发于肺栓塞的残余肺血栓,AcutePulmonaryArteryEmbolism,SouthwestHospital,EurJIntMed2019；23：379383,Residualpulmonarythromboemboliafteracutepulmonaryembolism继发于肺栓塞的残余肺血栓,AcutePulmonaryArteryEmbolism,SouthwestHospital,Lifelongtreatmentisappropriateif:,TheinitialPEwaslifethreateningPE威胁生存Thepatienthassignificantcardiorespiratorydisease患者有显著的心肺疾病Wherebyafurther,evensmall,PEcouldhavefatalconsequences;orthepatienthasasecond,unprovokedeventPE可能有致命性后果，或有再次无缘无故的事件,AcutePulmonaryArteryEmbolism,SouthwestHospital,INR达标:PE的复发是罕见的如果复发：增加warfarin、增大目标INR癌症患者（复发更常见）：转换为LMWH在抗凝治疗中仍存在DVT，或抗凝禁忌：腔静脉滤器（可回收式）,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,抗凝：严重出血并发症3%漏诊PE：死亡风险30%提示：确诊的PE、临床高度PE风险者均应抗凝，除非有明确禁忌症,ANAESTHESIAANDINTENSIVECAREMEDICINE2019；11:12,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,NewDrugReviewDabigatranEtexilate:AnOralDirectThrombinInhibitorfortheManagementofThromboembolicDisorders达比加群：口服的直接凝血酶抑制剂,ClinTher.2019;34:766787,TableI.Pertinentdruginteractionswithdabigatran,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,TableII.Pertinentclinicalstudiesontheuseofdabigatran.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,BISTROIBoehringerIngelheimStudyinThrombosisI;DEdabigatranetexilate;DVTdeepveinthrombosis;PEpulmonaryembolism;QDdaily;RE-NOVATEPreventionofVenousThromboembolismAfterTotalHipReplacement;VTEvenousthromboembolism;RE-MODELThromboembolismPreventionAfterKneeSurgery;RE-MOBILIZEDabigatranVersusEnoxaparininPreventingVenousThromboembolismFollowingTotalKneeArthroplasty;RE-COVERDabigatranVersusWarfarinintheTreatmentofAcuteVenousThromboembolism;INRinternationalnormalizedratio;PETROPreventionofEmbolicandThromboticEventsinPatientsWithPersistentAtrialFibrillation;AFatrialfibrillation;RE-LYRandomizedEvaluationofLong-termAnticoagulationTherapy;Postoppostoperation.*P0.05forenoxaparin.P0.05indicatingnon-inferiortoenoxoparin.P0.0001indicatingnon-inferiortowarfarin.P0.05significantlydifferentfromwarfarin.P0.001indicatingnon-inferiortowarfarin.P0.001indicatingsuperiortowarfarin.,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Thrombolysis溶栓,巨大PE：常伴心血管病，有或无紫绀、静脉怒张、搏动，P2亢进虽然确诊应该基于影象结果，因为大的PE危急，通常难以转送至放射科进行CTPA床旁UCG可提供有价值的信息：急性右心负荷过重不能解释的心肺衰竭病人，因为病情太不稳定，无法CTPA、甚至床旁UCG，假定基于危险评估和临床表现而拟诊PE：alteplase（阿替普酶）50mg巨大PE，显著或进行性血动力学不稳定（溶栓可能戏剧性改善血动力学和氧合状态病死率和PE复发率低于肝素疗法，但几天内血凝块的解析度则不如，缺乏头对头研究结果，meta-analysis倾向溶栓疗法，因为显著降低了病死率submassivePE患者，溶栓后显著减少了进CCU的需求程度,ANAESTHESIAANDINTENSIVECAREMEDICINE2019；11:12,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,溶栓剂和方案（Thrombolyticagentsandregimens）,Streptokinase250,000Uasaloadingdoseover30min,链激酶followedby100,000Uperhourover1224hAcceleratedregimen:1.5millionIUover2h,Urokinase4400Uperkilogramofbodyweightasaloadingdoseover10min,尿激酶followedby4400U/kg/hover1224hAcceleratedregimen:3millionUover2h,Alteplase100mgover2h阿替普酶Acceleratedregimen:0.6mg/kgover15min,ReteplaseTwobolusinjectionsof10U30minapart瑞替普酶,Tenecteplase3050mgbolusover510s替奈普酶adjustedforbodyweight:60kg:30mg6070kg:35mg7080kg:40mg8090kg:45mg90kg:50mg,SouthwestHospital,Nostudyhasshownasignificantdifferenceintheefficacyofdifferentthrombolyticagents尚无研究表明不同溶栓剂效果有显著差异Asuggestedprotocoloftwo10unitdosesofReteplase,separatedby30minutes,iseffectiveandsimple建议2个10u瑞替普酶，间隔30minThereisnoevidencethatusingacentralvenousorpulmonaryartery(PA)catheterforadministeringthrombolyticsconfersatreatmentadvantageoranyreductioninbleedingcomplications，mayresultinarterialinjury，pneumothorax没有证据表明使用CV/PA导管给药具有治疗优势和减少出血并发症，而可致动脉损伤、气胸Majorbleeding：10%vs.3%withheparininfusionalone,Intracerebralhaemorrhage：15min），或SBP持续显著下降(40mmHg）Mortalityexceeding25%(65%ifcardiopulmonaryresuscitationisrequired)65%需要CPR者，病死率超过25%AcuteRVfailureisaverycommonfeature急性RVF十分常见Theremayonlybeabriefwindowofopportunitytoidentifyandaddressthecondition可供识别和处理的时间窗很短Patientsremainatsignificantriskofdeathforseveraldaysafteranevent几天内死亡风险仍很高,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,SubmassivePE次大PETypicallydescribesotheracutePEs典型的急性PE症状Normalbloodpressure血压正常PatientsmayhaveevidenceofRVdysfunction(bestconfirmedwithechocardiography,butalsopossiblyshownonCT)右心室功能不全的症状（UCG，CT）Thissubgrouphasuptofourtimesthemortalityriskandincreasedratesofrecurrence,mayalsogoontodevelopshockorRVthrombus也可发生休克或RV血栓，则死亡增加4倍、复发风险增加Removeclotsuchasthrombolysismayhavearoleinthisgroup溶栓可能有作用Preventionofrecurrenceisapriority预防复发优先,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,AllotherpatientswithPE其他PE者Haemodynamicallystable血动力血稳定NormalRVfunction,RV功能正常Majoritytendtofollowanuneventfulcourse(180mmHg)Advancedliverdisease肝病晚期Infectiveendocarditis感染性心内膜炎Activepepticulcer活动性消化道溃疡,SouthwestHospital,Table1ContraindicationstofibrinolyticuseinPE,Cardiacarrest:1.Absolutecontraindications-None2.Relativecontraindications-Activeinternalbleeding-RecentintracranialbleedingMassivePE:1.Absolutecontraindications-Activeinternalbleeding-Recentintracranialbleeding2.Relativecontraindications-Intracranialtumororseizurehistory-Ischemicstokeuntil2months-Neurosurgerywithinpastmonth-Recentsurgerywithin10days-Punctureofnoncompressiblevesselwithin10days-Traumawithin15days-Uncontrolledhypertension(SBP180mmHg,DBP110mmHg)-Hemorrhagicdisorderofthrombocytopenia(180mmHg,DBP110mmHg)-Hemorrhagicdisorderorthrombocytopenia(65,GuidelinesandProgressontheDiagnosisandManagementofAcutePE,SouthwestHospital,Table4FibrinolyticdosingregimensinPE,Cardiacarrest:1.UK、SK、r-tpA(任一种)2.Alteplase(FDA-appointed)阿替普酶（FDA指定）a.50-mgIVbolus50mg弹丸式IVb.Mayrepeat50-mgIVbolusin15minifnoROSC15min内如未恢复，可重复1次3.Reteplase瑞替普酶a.20-UIVbolus20-UIV弹丸式IV3.Tenecteplase替奈普酶a.0.5-mg/kgIVbolus(max50mg)MassiveandsubmassivePE:1.Alteplase(FDAapproved)a.10-mgIVbolusb.Followedby90-mgIVillusionover2h2.Reteplasea.1