肌松药的使用复习进程

NeuromuscularmanagementandpatientoutcomesbyGlennMurphyM.D.2014ASA第一页，共44页。Postoperativeresidualneuromuscularblockadeisacommoncomplicationobservedinthepostanesthesiacareunit(PACU)aftergeneralanesthesia.Recentlarge-scaleclinicalinvestigationshavedemonstratedthatupto24%to42%ofsurgicalpatientsarriveinthePACUwithevidenceofincompleteneuromuscularrecovery.Althoughmostcliniciansarenowusingintermediate-actingmusclerelaxants,theriskofresidualneuromuscularblockdoesnotappeartobedecreasingovertime.第二页，共44页。术后肌松阻滞残留是全麻后发生在PACU的一个常见并发症。最近的大型临床研究显示有24%到42%的外科(wàikē)患者在达到PACU时，肌松恢复不完全。虽然很多临床大夫现在应用的是中效肌松药，不过肌松阻滞残余的风险似乎并没有因此而降低。第三页，共44页。Severallargedatabasestudieshaveshownanassociationbetweenneuromuscularblockingagent(NMBA)useandanincreasedriskofmorbidityandmortalityintheearlyperiodaftersurgery.RecentclinicaltrialshavedemonstratedthatresidualneuromuscularblockinthePACUresultsinairwayobstruction,hypoxemia,andpulmonarycomplicationsduringrecoveryfromgeneralanesthesia.PatientswithresidualblockareatriskforunpleasantsymptomsofmuscleweaknessandprolongedPACUadmissiontimes.第四页，共44页。很多大样本数据研究显示肌松药和术后早期并发症发生率和死亡率的增高有明显关系。最近的临床试验也显示全麻术后患者在PACU期间的肌松阻滞残留会导致气道梗阻、缺氧和呼吸系统(hūxīxìtǒnɡ)并发症。有肌松阻滞残留的患者也面临肌肉乏力的不适感和PACU停留时间延长的问题第五页，共44页。Carefulmanagementofneuromuscularblockadeintheoperatingroommayreducetheincidenceofpostoperativeresidualparalysisandthecomplicationsassociatedwithresidualblock.SeveralprinciplesrelatedtoNMBAdosing,monitoring,andreversalhavebeenshowntoreducetheriskofincompleteneuromuscularrecoveryinpostoperativepatients.Theaimofthisreviewistoprovidea“best-availableevidence”assessmentofmethodsthatcanbeusedbyclinicianstoreducetheriskofcomplicationsduetoresidualneuromuscularblockade.第六页，共44页。手术间内对肌松药使用的认真管理有可能降低术后肌无力的发生率和与肌松残留相关的并发症发生率。研究表明一些与NMBA剂量、监测和拮抗有关的管理原则(yuánzé)可以降低术后肌松恢复不完全的风险。这篇综述的目的是提供一个“好的和可行”的评估方法，从而指导临床大夫降低与肌松残留相关的并发症发生的风险。第七页，共44页。Q1:Doesqualitativeneuromuscularmonitoringreducetheriskofresidualblock?Asubjective(qualitative)visualortactileassessmentofamuscularresponsetoperipheralnervestimulationisthemostcommonmethodofneuromuscularmonitoringusedintheOR.Pedersenetal.randomized80subjectstoreceiveeitherTOFmonitoringornoneuromuscularmonitoring(clinicalcriteriasuchasbreathingormoving).MedianTOFratiosof0.75and0.79wereobservedinthetwogroupsonarrivaltothePACU(nodifference).

第八页，共44页。Q1:定性肌松监测可以(kěyǐ)降低肌松残留的发生风险吗？客观上感知患者对外周神经刺激的反应是手术间里最常用的一种肌松监测方法。Pedersen等将80名患者随机分配接受TOF监测或非肌松监测（临床标准：呼吸或活动动度）。达到PACU时两组患者的TOF中位值分别是0.75和0.79，没有区别。第九页，共44页。AsimilarstudydemonstratedthattheproportionofpatientswithTOFratios<0.7wassignificantlylessinamonitoredgroup(15%)comparedtounmonitoredpatients(47%).Anotherrandomizedtrialdemonstratedthattactileevaluationoftheresponsetodouble-burststimulation(DBS)reduced,butdidnoteliminate,theoccurrenceofresidualparalysis.SignificantlyfewerpatientsinthemonitoredgrouphadTOFratios<0.7(24%)comparedtotheunmonitoredgroup(57%).第十页，共44页。一项相似的研究显示：肌松监测组患者到达PACU时TOF<0.7的比例（15%）要明显低于没有监测组（47%）。另一项随机试验显示感觉患者对双爆发刺激（DBS）的反应可以降低，但不能消除(xiāochú)残留肌松的发生。有肌松监测组的患者TOF<0.7的概率（24%）要低于没有肌松监测组的患者（57%）。第十一页，共44页。Q2:Does

quantitativeneuromuscularmonitoringreducetheriskofresidualblock?Astudyshowedduring40patients,thereare50%patientsinthenomonitoringhadTOFratios<0.7inthePACU,comparedtoonly5.3%intheAMG(acceleromyograph)group.Aanotherstudyshowedthat17%ofpatientsinthenomonitoringgrouphadresidualblock(definedasaTOF<0.8)comparedtoonly3%intheAMGgroup.第十二页，共44页。Q2:定量肌松监测降低肌松残留的发生风险吗？一项研究显示在40例患者中，在PACU期间(qījiān)在非监测组有50%的患者TOF<0.7，而在加速度仪监测组只有5.3%的患者TOF<0.7.另一项研究显示非监测组有17%的患者有肌松残留（定义为TOF<0.8），而加速度仪组只有3%的患者有肌松残留第十三页，共44页。Inthelargeststudy,185patientswererandomizedtoreceiveeitherstandardqualitativemonitoring(peripheralnervestimulator)orAMGmonitoring(TOF-Watch).30%ofpatientsintheformergrouphadaTOFratio<0.9inthePACU,versusonly4.5%intheAMGgroup.在一项大样本研究中，185例患者(huànzhě)被随机分配为标准定性监测（外周神经刺激）或者AMG监测（TOF-Watch）。前一组中有30%的患者(huànzhě)在PACU期间TOF<0.9，而AMG组只有4.5%的患者(huànzhě)TOF<0.9第十四页，共44页。Q3:Can

neuromuscularmonitoringimpactpostoperativerecovery?Althoughthereisevidencethatqualitativemonitoringcanreducetheriskofpostoperativeresidualblock,atthepresenttimethereisnodatademonstrationthatthistypeofmonitoringimprovesclinicaloutcomes.Incontrast,thereisemergingevidencethatintraoperativequantitativemonitoringcanbeneficiallyimpactpostoperativerecoveryinsurgicalpatients.MortensenetalnotedthatpatientsrandomizedtoreceiveAMGmonitoringhadfewerclinicalsignsofmuscleweaknessinthePACU.第十五页，共44页。Q3:神经肌肉监测可以反应术后的恢复情况吗？虽然有证据(zhèngjù)表明定性的监测可以降低术后肌松残留的风险，不过目前，还是没有数据说明这种监测可以改善临床愈后。与此相反，有证据(zhèngjù)提示术中的肌松定量监测对手术患者的术后恢复有一定好处。Mortensen等发现接受AMG监测的患者在PACU期间很少表现出肌肉乏力的临床征象。第十六页，共44页。Astudyshowedthatasignificantlyhigherincidenceofhypoxemiaevents(oxygensaturation<90%)andairwayobstructionwasobservedintheperipheralnervestimulatorgroup(21.1%and11.1%)comparedtotheAMGgroup(0%and0%)inPACU.Patients

randomizedtoreceiveAMGmonitoringhadsignificantlyfewersymptomsofmuscleweaknessinthePACUduringthefirst60minutes,andoverallqualityofrecoveryatthetimePACUdischargewassignificantlyimprovedinthesepatients.第十七页，共44页。一项研究显示与AMG组（0%和0%）相比，仅接受外周神经刺激监测的患者在PACU期间(qījiān)发生低氧血症（SPO2<90%）和呼吸道梗阻的概率明显增高。AMG组的患者，在PACU期间(qījiān)的第一小时内，肌无力的症状较少，从PACU出去时的恢复质量也明显较高。第十八页，共44页。Q4:Shouldananticholinesterasereversalagentbeadministeredtomostpatientsattheendofsurgery?Anumberofstudieshaveindicatedahighriskofincompleteneuromuscularrecoveryifreversalagentsareomitted.

Caldwelletal.examinedtheincidenceofresidualblock1-4hoursafterasingleintubationdoseofvecuroniumwasgiven,approximatelyone-halfofpatientshadnotachievedaTOFratio>0.9fourhoursaftertheintubationdoseofvecuronium.第十九页，共44页。Q4:在手术结束时应该给大多数患者(huànzhě)使用抗胆碱酯酶药吗？一些研究提示如果不用抗胆碱酯酶药，那么肌力恢复不完全的风险会比较高。Caldwell等观察了给予单次插管剂量的维库溴铵后1-4小时的肌松残留发生率，在4小时后约一半的患者(huànzhě)达不到TOF>0.9的水平。第二十页，共44页。Q5:At

whatTOFcountwillneostigmineproducearapidandreliablereversal?SeveralinvestigationshaveexaminedthetimerequiredtoachieveaTOFratioof0.9orgreaterwhenneostigmineisadministeredatvariouslevelsofneuromuscularblock(TOFcountof1-4withTOFstimulation).Neostigmineshouldnotbeadministereduntilthereissomeevidenceofspontaneousneuromuscularrecovery(shouldnotbegivenataTOFcountof0-theconcentrationofNMBAattheneuromuscularjunctionittoohightocompetitivelyantagonize).第二十一页，共44页。Q5：在TOF计数多少时新斯的明可以产生比较迅速和可靠的肌松拮抗效果？一些研究观察了在不同肌松阻滞程度时（TOF刺激仪上TOF计数从1-4）给予新斯的明到达到(dádào)TOF0.9或更高值所需的时间。只有当自主呼吸开始恢复时，才可以给新斯的明（TOF计数是0时不能给新斯的明，这表明神经肌肉接头的非去极化肌松药浓度很高，很难被竞争性拮抗）第二十二页，共44页。Kimreversedpatientswithneostigmine(70ug/kg)ataTOFcountofeither1,2,3,or4.AtaTOFcountof1,themediantimetoachieveaTOFratioof0.9was28.6minutes(range8.8to75.8minutes)AtaTOFcountof4,themediantimetoachieveaTOFratioof0.9was9.5minutes(range5.1to26.4minutes).ItalsoshowedthatbeginningwithaTOFcount4,only55%ofpatientshadachievedaTOFratioof>0.9with10minutes.第二十三页，共44页。Kim分别在TOF计数为1，2，3，4时用新斯的明(70ug/kg)给患者进行拮抗。TOF是1时，TOF达到0.9的平均时间(shíjiān)是28.6分钟(8.8-75.8min)TOF是4时，TOF达到0.9的平均时间(shíjiān)是9.5分组(5.1-26.4min)如果在TOF是4时开始拮抗，仅有55%的患者可以在10min内TOF值达到>0.9第二十四页，共44页。KirkegaardetalshowedthatthetimesfromreversaluntilachievingaTOFratioof0.9were20.0(6.5to70.5)minutesataTOFcountof2and16.5(6.5-143.3)minutesataTOFcountof4.Thesestudiesdemonstratethatreversalofneuromuscularblockadeisnotrapidwithneostigmine(requiresapproximately15minutesataTOFcountof4attheendofsurgery).Inaddition,thereislargevariabilityinreversaltimes,evenataTOFcountof4.第二十五页，共44页。Kirkegaard等的研究显示在TOF值是2和4时，给予拮抗药到TOF达到0.9，分别需要20min(6.5-70.5)和16.5（6.5-143.3）。这些研究显示新斯的明的拮抗作用(zuòyòng)并不快（在手术结束TOF是4时，一般需要约15min）。另外，即使TOF计数为4时才开始拮抗，拮抗肌松作用(zuòyòng)所需的时间差异也很大。第二十六页，共44页。Q6:Areclinicalsignsreliableindicatorsofneuromuscularrecovery?Studiesinawakevolunteersandpostoperativesurgicalpatientshaveexaminedthepredictivevalueofthesetestsindeterminingwhetherfullrecoveryofmusclestrength(TOFratio>0.9)hasoccurred.Theabilitytomaintaina5-secondhead-liftisacommonly-usedtestofmusclerecoveryintheOR.Inastudyinwhich12awakevolunteersweregivenaninfusionofrocuronium,11of12volunteerswereabletomaintaina5-secondhead-liftataTOFratioof0.5.第二十七页，共44页。Q6：临床征象是肌松恢复的可靠指标吗？在清醒(qīngxǐng)志愿者和术后患者的一些研究调查了这些试验对肌松完全恢复（TOF>0.9）的预测价值。OR内常用的一个检测肌松恢复的试验是5-秒抬头试验在一项对12名清醒(qīngxǐng)志愿者的研究中，给与静注罗库溴铵，在12名志愿者中有11名可以在TOF是0.5时完成5-秒抬头试验。第二十八页，共44页。Inanotherinvestigation,12awakevolunteersweregivenaninfusionofmivicurium.AtaTOFrationof0.5,allofthevolunteerscouldspeak,openeyesandprotrudetongues,and8ofthe12couldmaintaina5-secondhead-liftandswallow.Inacohortstudy640surgicalpatientswereexaminedtheresidualblock(TOFratio<0.9),noneoftheeightclinicalsignstestsorcombinationsoftest,wereabletoreliabledetectthepresenceofresidualblock.Thesestudiesdemonstratethatclinicalsignsofmusclestrengthareinsensitiveindeterminingthepresenceorabsenceofincompleteneuromuscularrecovery.第二十九页，共44页。在另一项调查研究(yánjiū)中，12名清醒志愿者被静注了美维松，在TOF为0.5时，所有的志愿者都可以讲话，睁眼和伸舌。12个志愿者里有8名可以完成5-秒抬头试验和吞咽。在一项640例手术患者参与的队列研究(yánjiū)中，对这些患者TOF<0.9的肌松残留情况的研究(yánjiū)发现，8项临床征象没有一个或者几个联合起来可以可靠的发现肌松的残留作用。这些研究(yánjiū)表明用于判断肌力的临床体征并不是神经肌肉是否完全恢复的敏感指标。第三十页，共44页。Q7:Canresidualneuromuscularblockbereliablyexcludewithconventionalperipheralnervestimulators(qualitativeneuromuscularmonitoring)?Peripheralnervestimulatorsareoftenusedtodeterminedwhetherrecoveryofneuromuscularfunctionhasoccurredattheendofsurgery.IfnofadeisdetectedwithTOF,DBS,ortetanicstimulation,thenrecoveryofmusclestrengthisassumedtobecomplete.Studiesshowedthatcliniciansareunabletousetactileassessmenttoidentifyfadein55%ofcaseswhenTOFratioswerebetween0.4-0.7第三十一页，共44页。Q7：用传统的外周神经刺激器（定性肌松监测）是否可以有效的排除肌松阻滞(zǔzhì)残余？外周神经刺激器通常用来监测在手术结束时神经肌肉功能是否恢复功能。如果用TOF，DBS或强直刺激没有发现肌颤搐衰减，那么认为肌力恢复完全。研究显示当TOF在0.4-0.7时，临床大夫用触觉的方法难以发现55%的患者还有肌颤搐的衰减现象。第三十二页，共44页。RelativesurveysSurveyshaveconsistentlydemonstratedthatmostcliniciansdonotroutinelymonitorpatientswithperipheralnervestimulatorsintheOR.Asurveyshowedthat24.3%ofeuropeanrespondentsindicatedthatqualitativemonitoringwasnotavailableintheirdepartment,andifsuchmonitoringwasavailable,itwasoftensharedbetween2-3room.Despitehighqualitystudiesdemonstratingabeneficialeffectofquantitativemonitoringontheincidenceofresidualneuromuscularblockade,fewcliniciansroutinelyusethistypeofmonitoring.第三十三页，共44页。相关调查：很多调查都发现多数临床大夫在OR并不常规用外周神经刺激器监测患者。一项调查显示有24.3%的欧洲麻醉医师指出他们的科室没有定性肌松监测仪，而且，即使有这种仪器，一般也是2-3个手术间配备一个。虽然研究显示定量的肌松监测对于术后肌松阻滞(zǔzhì)残留的发现有好处，不过很少有临床大夫常规使用这项监测。第三十四页，共44页。Surveyssuggestthatanticholinesterasereversalagentsarenotroutinelyusedbyanesthesiologists.InthesurveybyNaguib,only18%ofEuropeanrespondentsand34%ofunitedstatesrespondentsnotedthattheyalwaysusedananticholinesteraseagentattheendofsurgery.Morethatone-halfoftherespondentsfromtheUSstatedthatrapidandreliablereversalcouldbeachievedataTOFcountof2orless.Furthermore,morethanone-halfoftheeuropeanrespondentsstatedthattheytypicallyallow5minutesorlessbetweenthetimeofneostigmineadministrationandtrachealextubation.第三十五页，共44页。调查发现麻醉(mázuì)医师并没有常规用抗胆碱酯酶药拮抗肌松作用。在Naguib的调查中，仅18%的欧洲麻醉(mázuì)大夫和34%的美国麻醉(mázuì)大夫提出他们在手术结束的时候会常规用抗胆碱酯酶药。超过一半的美国麻醉(mázuì)医师认为在TOF是2或更低时进行肌松拮抗是可以很快起效，并且拮抗效果满意。而且超过一般的欧洲麻醉(mázuì)医师指出从他们给拮抗药到拔管的时间通常是5分钟或者更短。第三十六页，共44页。Onthebasisofsurveysthathavebeenpublishedfromaroundtheworld,thereappearstobeasignificantdifferencebetweenpublished“best-evidence”practicesandtheneuromuscularmanagementstrategiesusedbycliniciansindailypractice.基于目前已发表的调查，临床大夫在日常工作中所做的肌松管理(guǎnlǐ)和已公布的“最佳证据”临床指南之间还有明显的差别。第三十七页，共44页。Conclusionsandrecommendations1.tactileevaluationofTOFandDBSfadereduces(butnoteliminate)theincidenceanddegreeofpostoperativeresidualparalysiscomparedwiththeuseofclinicalcriteriatoassessreadinessfortrachealextubation2.Toexcludewithcertaintythepossibilityofresidualparalysisinpatientsatrisk,cliniciansshoulduseobjective(quantitative)neuromuscularmonitoringtests.3.Ideally,neuromuscularfunctionshouldbemonitoredobjectively(quantitatively)inallpatientsreceivingNMBAs.第三十八页，共44页。结论和推荐1.与用临床征象来判断拔管的时间相比，通过对TOF和DBS导致的肌颤搐衰减的触觉评估可以判断降低术后肌松残留的发生率。2.为了排除肌松残留可能的风险(fēngxiǎn)，临床医师应该进行客观（定量）的肌松监