肺梗塞指南

2014ESCGuidelinesonthediagnosisandmanagementofacutepulmonaryembolism推荐类别和证据级别推荐类别和证据级别对推荐类别的表述I类：指那些已证实和(或)一致公认有益、有用和有效的操作或治疗，推荐使用。Ⅱ类：指那些有用／有效的证据尚有矛盾或存在不同观点的操作或治疗。Ⅱa类：有关证据／观点倾向于有用／有效，应用这些操作或治疗是合理的。Ⅱb类：有关证据／观点尚不能充分证明有用／有效，可以考虑应用。Ⅲ类：指那些已证实和(或)一致公认无用和(或)无效，并对一些病例可能有害的操作或治疗，不推荐使用。对证据来源的水平表达如下：证据水平A：资料来源于多项随机临床试验或荟萃分析。证据水平B：资料来源于单项随机临床试验或多项非随机对照研究。证据水平C：仅为专家共识意见和(或)小规模研究、回顾性研究、注册研究。2014ESCGUIDELINES简介基本概念流行病学易患因素自然病程病理生理临床肺梗塞严重分级基本概念肺栓塞（pulmonaryembolism,PE):是以各种栓子堵塞肺动脉系统为其发病原因的一组疾病或临床综合征的总称，包括肺血栓栓塞、脂肪栓塞、羊水栓塞、空气栓塞等。肺血栓栓塞症（pulmonarythromboembolism,PTE):是指来源于静脉系统或右心血栓堵塞肺动脉或其分枝引起肺循环障碍的临床和病理生理综合征。肺动脉血栓形成（pulmonarythrombosis）指肺动脉病变基础上（如肺血管炎、白塞氏病等）原位血栓形成，多见于肺小动脉，并非外周静脉血栓脱落所致，临床不易与肺栓塞相鉴别。深静脉血栓形成（deepvenousthrombosis,DVT):纤维蛋白、血小板、红细胞等血液成份在深静脉管腔内形成凝血块（血栓）。静脉血栓栓塞症（venousthrombolism,VTE):PTE和DVT是同一疾病过程中两个不同阶段，统称为VTE.Epidemiologyover317000deathswererelatedtoVTEinsixcountriesoftheEuropeanUnion(withatotalpopulationof454.4million)in2004:34%presentedwithsuddenfatalPE59%weredeathsresultingfromPEthatremainedundiagnosedduringlife7%ofthepatientswhodiedearlywerecorrectlydiagnosedwithPEbeforedeath.(CohenAT,Venousthromboembolism(VTE)inEurope.ThenumberofVTEeventsandassociatedmorbidityandmortality.ThrombHaemost2007;98(4):756–764.)流行病学急性PE是VTE最严重的临床表现，多数情况下PE继发于DVT，现有的流行病学多将VTE作为一个整体进行危险因素、自然病程等研究，其年发病率100-200/10万人。PE可以没有症状，有时偶然发现才得以确诊，甚至某些PE患者的首发表现就是猝死，因而很难获得准确的PE流行病学资料。2004年总人口为4.544亿的欧盟6国，与PE有关的死亡超过317,000例。其中，突发致命性PE占34％，其中死前未能确诊的占59％，仅有7％的早期死亡病例在死亡前得以确诊。PE的发生风险与年龄增加相关，40岁以上人群，每增龄10岁PE增加约1倍。Predisposingfactorssurgerytraumaimmobilizationpregnancyoralcontraceptiveusehormonereplacementtherapycancerobesityinfectionandcentralvenouslines易患因素强易患因素（OR＞10）下肢骨折3个月内因心力衰竭、心房颤动或心房扑动入院髋关节或膝关节置换术严重创伤3月内发生过心肌梗死既往VTE脊髓损伤中等易患因素（OR2－9）膝关节镜手术自身免疫疾病输血中心静脉置管化疗慢性心力衰竭或呼吸衰竭应用促红细胞生成因子激素替代治疗体外受精感染（尤其呼吸系统、泌尿系统感染或HIV感染）炎症性肠道疾病肿瘤口服避孕药卒中瘫痪产后浅静脉血栓遗传性血栓形成倾向弱易患因素（OR＜2）卧床>3天糖尿病高血压久坐不动（如长时间乘车或飞机旅行）年龄增长腹腔镜手术（如腹腔镜下胆囊切除术）肥胖妊娠静脉曲张NaturalhistoryThefirststudiesonthenaturalhistoryofVTEwerecarriedoutinthesettingoforthopaedicsurgeryduringthe1960s.RegistriesandhospitaldischargedatasetsofunselectedpatientswithPEorVTEyielded30-dayall-causemortalityratesbetween9%and11%,andthree-monthmortalityrangingbetween8.6%and17%.Basedonhistoricaldata,thecumulativeproportionofpatientswithearlyrecurrenceofVTE(onanticoagulanttreatment)amountsto2.0%at2weeks,6.4%at3monthsand8%at6months.ThecumulativeproportionofpatientswithlaterecurrenceofVTE(aftersixmonths,andinmostcasesafterdiscontinuationofanticoa-gulation)hasbeenreportedtoreach13%at1year,23%at5years,and30%at10years.RecurrenceismorefrequentaftermultipleVTEepi-sodesasopposedtoasingleevent,andafterunprovokedVTEasopposedtothepresenceoftemporaryriskfactors.ElevatedD-dimerlevels,eitherduringorafterdiscontinuationofanticoagulation,indicateanincreasedriskofrecurrence.自然病程PE/VTE患者30天全因死亡率为9％-11％，3个月全因死亡率为8.6％-17％。VTE存在复发的风险。VTE早期复发的累计比例2周时为2.0％，3个月时为6.4％，6个月时为8％。复发率在前2周最高，随后逐渐下降，活动期肿瘤和抗凝剂未快速达标是复发风险增高的独立预测因素。VTE晚期复发（6个月后，多数在停用抗凝剂后）的累计比例1年时达13％，5年时达23％，10年时达30％。有VTE复发史的患者更易反复发作，无明显诱因的VTE较有暂时性危险因素的VTE更易复发。抗凝治疗期间或停药后D二聚体水平升高者复发风险增高。PathophysiologyAcutePEinterfereswithboththecirculationandgasexchange.CIRCULATIONPulmonaryarterypressureincreasesonlyifmorethan30–50%ofthetotalcross-sectionalareaofthepulmonaryarterialbedisoccludedbythromboemboli.TheabruptincreaseinpulmonaryvascularresistanceresultsinRVdilation,whichaltersthecontractilepropertiesoftheRVmyocar-diumviatheFrank-Starlingmechanism.TheprolongationofRVcontractiontimeintoearlydiastoleintheleftventricleleadstoleftwardbowingoftheinterventricularseptum.Andthismayleadtoareductionofthecardiacoutputandcontributetosystemichypotensionandhaemodynamicinstability.RESPIRATORYFAILURELowcardiacoutputresultsindesat-urationofthemixedvenousblood.Inaddition,zonesofreducedflowinobstructedvessels,combinedwithzonesofoverflowinthecapillarybedservedbynon-obstructedvessels,resultinventila-tion–perfusionmismatch,whichcontributestohypoxaemia.Inaboutone-thirdofpatients,right-to-leftshuntingthroughapatentforamenovalecanbedetectedbyechocardiography病理生理1.　血流动力学改变：PE可导致肺循环阻力增加，肺动脉压升高。肺血管床面积减少25%～30%时肺动脉平均压轻度升高，肺血管床面积减少30%～40%时肺动脉平均压可达30mmHg以上，右室平均压可升高；肺血管床面积减少40%～50%时肺动脉平均压可达40mmHg，右室充盈压升高，心指数下降；肺血管床面积减少50%～70%可出现持续性肺动脉高压；肺血管床面积减少＞85%可导致猝死。PE时血栓素A2等物质释放，可诱发血管收缩。解剖学阻塞和血管收缩导致肺血管阻力增加，动脉顺应性下降。病理生理2.　右心功能：肺血管阻力突然增加导致右心室压力和容量增加、右心室扩张，使室壁张力增加、肌纤维拉伸，右心室收缩时间延长；神经体液激活导致变力和变时刺激。上述代偿机制与体循环血管收缩共同增加了肺动脉压力，以增加阻塞肺血管床的血流，由此暂时稳定体循环血压。但这种即刻的代偿程度有限，未预适应的薄壁右心室无法产生40mmHg以上的压力以抵抗平均肺动脉压，最终发生右心功能不全。右室壁张力增加使右冠状动脉相对供血不足，同时右室心肌氧耗增多，可导致心肌缺血，进一步加重右心功能不全。病理生理3.　心室间相互作用：右心室收缩时间延长，室间隔在左心室舒张早期突向左侧，右束支传导阻滞可加重心室间不同步，引起左心室舒张早期充盈受损，右心功能不全导致左心回心血量减少，使心输出量降低，造成体循环低血压和血液动力学不稳定。病理生理4.　呼吸功能：心输出量的降低引起混合静脉血氧饱和度降低。阻塞血管和非阻塞血管毛细血管床的通气/血流比例失调，导致低氧血症。由于右心房与左心房之间压差倒转，1/3的患者超声可以检测到经过卵圆孔的右向左分流，引起严重的低氧血症，并增加反常栓塞和卒中的风险。Clinicalclassificationofpulmonaryembolismseverity诊断临床表现临床预测D-dimer测定CTA肺灌注/通气扫描肺血管造影MRA心脏超声加压静脉超声诊断策略可疑高危肺梗可疑非高危肺梗临床表现PollackCV,SchreiberD,GoldhaberSZ,SlatteryD,FanikosJ,O’NeilBJ,ThompsonJR,HiestandB,BrieseBA,PendletonRC,MillerCD,KlineJA.Clinicalcharacteristics,management,andoutcomesofpatientsdiagnosedwithacutepulmonaryembolismintheemergencydepartment:initialreportofEMPEROR(MulticenterEmergencyMedicinePulmonaryEmbolismintheRealWorldRegistry).JAmCollCardiol2011;57(6):700–706.临床预测规则WellsPS,AndersonDR,RodgerM,GinsbergJS,KearonC,GentM,TurpieAG,BormanisJ,WeitzJ,ChamberlainM,BowieD,BarnesD,HirshJ.Derivationofasimpleclinicalmodeltocategorizepatientsprobabilityofpulmonaryembolism:increasingthemodelsutilitywiththeSimpliREDD-dimer.ThrombHaemost2000;83(3):416–420.临床预测规则LeGalG,RighiniM,RoyPM,SanchezO,AujeskyD,BounameauxH,PerrierA.Predictionofpulmonaryembolismintheemergencydepartment:therevisedGenevascore.AnnInternMed2006;144(3):165–171.D-dimer测定AnumberofD-dimerassaysareavailable.Thequantitativeenzyme-linkedimmunosorbentassay(ELISA)orELISA-derivedassayshaveadiagnosticsensitivityof95%orbetterandcanthereforebeusedtoexcludePEinpatientswitheitheraloworamoderatepre-testprobability.Quantitativelatex-derivedassaysandawhole-bloodagglutinationassayhaveadiagnosticsensitivity,95%andarethusoftenreferredtoasmoderatelysensitive.Inoutcomestudies,thoseassaysprovedsafeinrulingoutPEinPE-unlikelypatientsaswellasinpatientswithalowclinicalprobability.ThespecificityofD-dimerinsuspectedPEdecreasessteadilywithage,toalmost10%inpatients.80years.Inarecentmeta-analysis,age-adjustedcut-offvalues(agex10mg/Labove50years)allowedincreasingspecificityfrom34–46%whileretainingasensitivityabove97%.WellsPS,AndersonDR,RodgerM,StiellI,DreyerJF,BarnesD,ForgieM,KovacsG,WardJ,KovacsMJ.Excludingpulmonaryembolismatthebedsidewithoutdiagnosticimaging:managementofpatientswithsuspectedpulmonaryembolismpresentingtotheemergencydepartmentbyusingasimpleclinicalmodelandd-dimer.AnnInternMed2001;135(2):98–107.DiNisioM,SquizzatoA,RutjesAW,Bu¨llerHR,ZwindermanAH,BossuytPM.DiagnosticaccuracyofD-dimertestforexclusionofvenousthromboembolism:asystematicreview.JThrombHaemost2007;5(2):296–304.RighiniM,GoehringC,BounameauxH,PerrierA.Effectsofageontheperformanceofcommondiagnostictestsforpulmonaryembolism.AmJMed2000;109(5):357–361.SchoutenHJ,GeersingGJ,KoekHL,ZuithoffNP,JanssenKJ,DoumaRA,vanDeldenJJ,MoonsKG,ReitsmaJB.DiagnosticaccuracyofconventionalorageadjustedD-dimercut-offvaluesinolderpatientswithsuspectedvenousthromboembolism:systematicreviewandmeta-analysis.BMJ2013;346:f2492.CarrierM,RighiniM,DjurabiRK,HuismanMV,PerrierA,WellsPS,RodgerM,WuilleminWA,LeGalG.VIDASD-dimerincombinationwithclinicalpre-testprobabilitytoruleoutpulmonaryembolism.Asystematicreviewofmanagementoutcomestudies.ThrombHaemost2009;101(5):886–892.D-dimer测定CTA（Computedtomographicpulmonaryangiography）AnegativeMDCTisanadequatecriterionforexcludingPEinpatientswithanon-highclinicalprobabilityofPE.WhetherpatientswithanegativeCTandahighclinicalprobabilityshouldbefurtherinvestigatediscontroversial.ThepositivepredictivevalueofMDCTislowerinpatientswithalowclinicalprobabilityofPE.Theclinicalsignificanceofisolatedsub-segmentalPEonCTangiographyisquestionable.ComputedtomographicvenographyhasbeenadvocatedasasimplewaytodiagnoseDVTinpatientswithsuspectedPE,asitcanbecombinedwithchestCTangiographyasasingleprocedure,usingonlyoneintravenousinjectionofcontrastdye.AsCTvenographyandCUSyieldedsimilarresultsinpatientswithsignsorsymptomsofDVTinPIOPEDII,ultrasonographyshouldbeusedinsteadofCTvenographyifindicated.CTA肺灌注/通气扫描InacutePE,ventilationisexpectedtobenormalinhypoperfusedsegments(mismatch).145,146Lungscanresultsarefrequentlyclassified:normalscan(excludingPE),highprobabilityscan(considereddiagnosticofPEinmostpatients),andnon-diagnosticscan.135Thehighfrequencyofnon-diagnosticintermediateprobabilityscanshasbeenacauseforcriticism,becausetheyindicatethenecessityforfurtherdiagnostictesting.AndersonDR,KahnSR,RodgerMA,KovacsMJ,MorrisT,HirschA,LangE,StiellI,KovacsG,DreyerJ,DennieC,CartierY,BarnesD,BurtonE,PleasanceS,SkedgelC,O’RoukeK,WellsPS.Computedtomographicpulmonaryangiographyvs.ventilation-perfusionlungscanninginpatientswithsuspectedpulmonaryembolism:arandomizedcontrolledtrial.JAMA2007;298(23):2743–2753.AldersonPO.Scintigraphicevaluationofpulmonaryembolism.EurJNuclMed1987;13Suppl:S6–10.肺灌注/通气扫描肺血管造影Pulmonaryangiographyhasfordecadesremainedthe‘goldstandard’forthediagnosisorexclusionofPE,butisrarelyperformednowasless-invasiveCTangiographyofferssimilardiagnosticaccuracy.Pulmonaryangiographyismoreoftenusedtoguidepercutaneouscatheter-directedtreatmentofacutePE.Pulmonaryangiographyisnotfreeofrisk.Inastudyof1111patients,procedure-relatedmortalitywas0.5%,majornon-fatalcomplicationsoccurredin1%,andminorcomplicationsin5%.vanBeekEJ,ReekersJA,BatchelorDA,BrandjesDP,Bu¨llerHR.Feasibility,safetyandclinicalutilityofangiographyinpatientswithsuspectedpulmonaryembolism.EurRadiol1996;6(4):415–419.SteinPD,AthanasoulisC,AlaviA,GreenspanRH,HalesCA,SaltzmanHA,VreimCE,TerrinML,WegJG.Complicationsandvalidityofpulmonaryangiographyinacutepulmonaryembolism.Circulation1992;85(2):462–468.MRAthistechnique,althoughpromising,isnotyetreadyforclinicalpracticeduetoitslowsensitivity,highproportionofinconclusiveMRAscans,andlowavailabilityinmostemergencysettings.Thehypothesis—thatanegativeMRAcombinedwiththeabsenceofproximalDVTonCUSmaysafelyruleoutclinicallysignificantPE—isbeingtestedinamulticentreoutcomestudy(ClinicalTrials.govNCT02059551).RevelMP,SanchezO,CouchonS,PlanquetteB,HernigouA,NiarraR,MeyerG,ChatellierG.Diagnosticaccuracyofmagneticresonanceimagingforanacutepulmonaryembolism:resultsofthe‘IRM-EP’study.JThrombHaemost2012;10(5):743–750.SteinPD,ChenevertTL,FowlerSE,GoodmanLR,GottschalkA,HalesCA,HullRD,JablonskiKA,LeeperKVJr.,NaidichDP,SakDJ,SostmanHD,TapsonVF,WegJG,WoodardPK.Gadolinium-enhancedmagneticresonanceangiographyforpulmonaryembolism:amulticenterprospectivestudy(PIOPEDIII).AnnInternMed2010;152(7):434–3.心脏超声AcutePEmayleadtoRVpressureoverloadanddysfunction,whichcanbedetectedbyechocardiography.RVdilationisfoundinatleast25%ofpatientswithPE,anditsdetection,eitherbyechocardiographyorCT,isusefulforriskstratificationofthedisease.Echocardiographicfindings—basedeitheronadisturbedRVejectionpattern(so-called‘60–60sign’)oroncontractilityoftheRVfreewallcomparedwiththeRVapex(‘McConnellsign’)—werereportedtoretainahighpositivepredictivevalueforPE,eveninthepresenceofpre-existingcardiorespiratorydisease.175Echocardiographicexaminationisnotrecommendedaspartofthediagnosticwork-upinhaemodynamicallystable,normotensivepatientswithsuspected(nothigh-risk)PE.157Thisisincontrasttosuspectedhigh-riskPE,inwhichtheabsenceofechocardiographicsignsofRVoverloadordysfunctionpracticallyexcludesPEasthecauseofhaemodynamicinstability.Conversely,inahaemodynamicallycompromisedpatientwithsuspectedPE,unequivocalsignsofRVpressureoverloadanddysfunctionjustifyemergencyreperfusiontreatmentforPEifimmediateCTangiographyisnotfeasible.182心脏超声Mobilerightheartthrombiaredetectedbytransthoracicortransoesophagealechocardiography(orbyCTangiography)inlessthan4%ofunselectedpatientswithPE,183–185buttheirprevalencemayreach18%intheintensivecaresetting.185Consequently,transoesophagealechocardiographymaybeconsideredwhensearchingforemboliinthemainpulmonaryarteriesinspecificclinicalsituations,188,189anditcanbeofdiagnosticvalueinhaemodynamicallyunstablepatientsduetothehighprevalenceofbilateralcentralpulmonaryemboliinmostofthesecases.190加压静脉超声Inthemajorityofcases,PEoriginatesfromDVTinalowerlimb.Nowadays,lowerlimbCUShaslargelyreplacedvenographyfordiagnosingDVT.InthesettingofsuspectedPE,CUScanbelimitedtoasimplefourpointexamination(groinandpoplitealfossa).TheprobabilityofapositiveproximalCUSinsuspectedPEishigherinpatientswithsignsandsymptomsrelatedtothelegveinsthaninasymptomaticpatients.临床预测规则WellsPS,AndersonDR,RodgerM,GinsbergJS,KearonC,GentM,TurpieAG,BormanisJ,WeitzJ,ChamberlainM,BowieD,BarnesD,HirshJ.Derivationofasimpleclinicalmodeltocategorizepatientsprobabilityofpulmonaryembolism:increasingthemodelsutilitywiththeSimpliREDD-dimer.ThrombHaemost2000;83(3):416–420.临床预测规则LeGalG,RighiniM,RoyPM,SanchezO,AujeskyD,BounameauxH,PerrierA.Predictionofpulmonaryembolismintheemergencydepartment:therevisedGenevascore.AnnInternMed2006;144(3):165–171.诊断策略诊断策略AreasofuncertaintyThediagnosticvalueandclinicalsignificanceofsub-segmentaldefectsonMDCTarestillunderdebatThereisalsogrowingevidencesuggestingover-diagnosisofPE.206Arandomizedcomparisonshowedthat,althoughCTdetectedPEmorefrequentlythanV/Qscanning,three-monthoutcomesweresimilar,regardlessofthediagnosticmethodused.Someexpertsbelievethatpatientswithincidental(unsuspected)PEonCTshouldbetreated,144especiallyiftheyhavecancerandaproximalclot,butsolidevidenceinsupportofthisrecommendationislacking.AndersonDR,KahnSR,RodgerMA,KovacsMJ,MorrisT,HirschA,LangE,StiellI,KovacsG,DreyerJ,DennieC,CartierY,BarnesD,BurtonE,PleasanceS,SkedgelC,O’RoukeK,WellsPS.Computedtomographicpulmonaryangiographyvs.ventilation-perfusionlungscanninginpatientswithsuspectedpulmonaryembolism:arandomizedcontrolledtrial.JAMA2007;298(23):2743–2753.CarrierM,RighiniM,WellsPS,PerrierA,AndersonDR,RodgerMA,PleasanceS,LeGalG.Subsegmentalpulmonaryembolismdiagnosedbycomputedtomography:incidenceandclinicalimplications.Asystematicreviewandmeta-analysisofthemanagementoutcomestudies.JThrombHaemost2010;8(8):1716–1722.SteinPD,GoodmanLR,HullRD,DalenJE,MattaF.Diagnosisandmanagementofisolatedsubsegmentalpulmonaryembolism:reviewandassessmentoftheoptions.ClinApplThrombHemost2012;18(1):20–26.预后评估临床参数经心超或CTA获得的右心室影像学结果实验室数据最初和简化的肺栓塞严重程度指数（PESI）经心超或CTA获得的右心室影像学结果实验室数据Other(non-cardiac)laboratorybiomarkersElevatedserumcreatininelevelsandadecreased(calculated)glomerularfiltrationratearerelatedto30-dayall-causemortalityinacutePE.Elevatedneutrophilgelatinase-associatedlipocalin(NGAL)andcystatinC,bothindicatingacutekidneyinjury,havealsobeenfoundtobeofprognosticvalue.ElevatedD-dimerconcentrationswereassociatedwithincreasedshort-termmortalityinsomestudies,whilelevels,1500ng/mLhadanegativepredictivevalueof99%forexcludingthree-monthall-causemortality.KostrubiecM,ŁabykA,Pedowska-WłoszekJ,PachoS,WojciechowskiA,JankowskiK,Ciurzyn´skiM,PruszczykP.Assessmentofrenaldysfunctionimprovestroponin-basedshort-termprognosisinpatientswithacutesymptomaticpulmonaryembolism.JThrombHaemost2010;8(4):651–658.KostrubiecM,ŁabykA,Pedowska-WłloszekJ,Dzikowska-DiduchO,WojciechowskiA,Garlin´skaM,Ciurzyn´skiM,PruszczykP.Neutrophilgelatinase-associatedlipocalin,cystatinCandeGFRindicateacutekidneyinjuryandpredictprognosisofpatientswithacutepulmonaryembolism.Heart2012;98(16):1221–1228.AujeskyD,RoyPM,GuyM,CornuzJ,SanchezO,PerrierA.PrognosticvalueofD-dimerinpatientswithpulmonaryembolism.ThrombHaemost2006;96(4):478–482.预后评估策略治疗循环和呼吸支持抗凝治疗肠外抗凝VIT-K拮抗剂新型口服抗凝药溶栓治疗外科血栓清除术经皮导管介入治疗静脉滤网早期出院和家庭治疗治疗策略肺梗高危治疗肺梗非高危治疗循环和呼吸支持ExperimentalstudiesindicatethataggressivevolumeexpansionisofnobenefitandmayevenworsenRVfunctionbycausingmechanicaloverstretch,orbyreflexmechanismsthatdepresscontractility.Ontheotherhand,modest(500mL)fluidchallengemayhelptoincreasecardiacindexinpatientswithPE,lowcardiacindex,andnormalBP.NorepinephrineappearstoimproveRVfunctionviaadirectpositiveinotropiceffect,whilealsoimprovingRVcoronaryperfusionbyperipheralvascularalpha-receptorstimulationandtheincreaseinsystemicBP.Basedontheresultsofsmallseries,theuseofdobutamineand/ordopaminemaybeconsideredforpatientswithPE,lowcardiacindex,andnormalBP;however,raisingthecardiacindexabovephysiologicalvaluesmayaggravatetheventilation–perfusionmismatchbyfurtherredistributingflowfrom(partly)obstructedtounobstructedvessels.Epinephrinecombinesthebeneficialpropertiesofnorepinephrineanddobutamine,withoutthesystemicvasodilatoryeffectsofthelatter.Accordingtodatafromsmallclinicalstudies,inhalationofnitricoxidemayimprovethehaemodynamicstatusandgasexchangeofpatientswithPE.MercatA,DiehlJL,MeyerG,TeboulJL,SorsH.Hemodynamiceffectsoffluidloadinginacutemassivepulmonaryembolism.CritCareMed1999;27(3):540–544.ManierG,CastaingY.Influenceofcardiacoutputonoxygenexchangeinacutepulmonaryembolism.AmRevRespirDis1992;145(1):130–136.CapellierG,JacquesT,BalvayP,BlascoG,BelleE,BaraleF.Inhalednitricoxideinpatientswithpulmonaryembolism.IntensiveCareMed1997;23(10):1089–1092.循环和呼吸支持thepositiveintrathoracicpressureinducedbymechanicalventilationmayreducevenousreturnandworsenRVfailureinpatientswithmassivePE;therefore,positiveend-expiratorypressureshouldbeappliedwithcaution.ExperimentalevidencesuggeststhatextracorporealcardiopulmonarysupportcanbeaneffectiveprocedureinmassivePE.KjaergaardB,RasmussenBS,deNeergaardS,RasmussenLH,KristensenSR.Extracorporealcardiopulmonarysupportmaybeanefficientrescueofpatientsaftermassivepulmonaryembolism.Anexperimentalporcinestudy.ThrombRes2012;129(4):e147–e151.抗凝治疗Thestandarddurationofanticoagulationshouldcoveratleast3months.Withinthisperiod,acute-phasetreatmentconsistsofadministeringparenteralanticoagulation[unfractionatedheparin(UFH),LMWHorfondaparinux]overthefirst5–10days.ParenteralheparinshouldoverlapwiththeinitiationofavitaminKantagonist(VKA);alternatively,itcanbefollowedbyadministrationofoneoftheneworalanticoagulants:dabigatranoredoxaban.Ifrivaroxabanorapixabanisgiveninstead,oraltreatmentwithoneoftheseagentsshouldbestarteddirectlyoraftera1–2dayadministrationofUFH,LMWHorfondaparinux.肠外抗凝InpatientswithhighorintermediateclinicalprobabilityforPE,parenteralanticoagulationshouldbeinitiatedwhilstawaitingtheresultsofdiagnostictests.UFHisrecommendedforpatientsinwhomprimaryreperfusionisconsidered,aswellasforthosewithseriousrenalimpairment(creatinineclearance,30mL/min),orsevereobesity.LMWHneedsnoroutinemonitoring,butperiodicmeasurementofanti-factorXaactivity(anti-Xalevels)maybeconsideredduringpregnancy.279Peakvaluesofanti-factorXaactivityshouldbemeasured4hoursafterthelastinjectionandtroughvaluesjustbeforethenextdoseofLMWHwouldbedue;thetargetrangeis0.6–1.0IU/mLfortwice-dailyadministration,and1.0–2.0IU/mLforonce-dailyadministration.280FondaparinuxisaselectivefactorXainhibitoradministeredoncedailybysubcutaneousinjectionatweight-adjusteddoses,withouttheneedformonitoringVIT-K拮抗剂Oralanticoagulantsshouldbeinitiatedassoonaspossible,andpreferablyonthesamedayastheparenteralanticoagulant.VKAshavebeenthe‘goldstandard’inoralanticoagulationformorethan50yearsandwarfarin,acenocoumarol,phenprocoumon,phenindioneandflunidioneremainthepredominantanticoagulantsprescribedforPE.AnticoagulationwithUFH,LMWH,orfondaparinuxshouldbecontinuedforatleast5daysanduntiltheinternationalnormalizedratio(INR)hasbeen2.0–3.0fortwoconsecutivedays.DeCaterinaR,HustedS,WallentinL,AndreottiF,ArnesenH,BachmannF,BaigentC,HuberK,JespersenJ,KristensenSD,LipGY,MoraisJ,RasmussenLH,SiegbahnA,VerheugtFW,WeitzJI.VitaminKantagonistsinheartdisease:Currentstatusandperspectives(SectionIII).PositionPaperoftheESCWorkingGrouponThrombosis-TaskForceonAnticoagulantsinHeartDisease.ThrombHaemost2013;110(6):1087–1107.BritishThoracicSociety.Optimumdurationofanticoa