肌松藥的使用課件

NeuromuscularmanagementandpatientoutcomesbyGlennMurphyM.D.2014ASANeuromuscularmanagementandpPostoperativeresidualneuromuscularblockadeisacommoncomplicationobservedinthepostanesthesiacareunit(PACU)aftergeneralanesthesia.Recentlarge-scaleclinicalinvestigationshavedemonstratedthatupto24%to42%ofsurgicalpatientsarriveinthePACUwithevidenceofincompleteneuromuscularrecovery.Althoughmostcliniciansarenowusingintermediate-actingmusclerelaxants,theriskofresidualneuromuscularblockdoesnotappeartobedecreasingovertime.Postoperativeresidualneuromu2術(shù)后肌松阻滯殘留是全麻后發(fā)生在PACU的一個常見并發(fā)癥。最近的大型臨床研究顯示有24%到42%的外科患者在達到PACU時，肌松恢復(fù)不完全。雖然很多臨床大夫現(xiàn)在應(yīng)用的是中效肌松藥，不過肌松阻滯殘余的風險似乎并沒有因此而降低。術(shù)后肌松阻滯殘留是全麻后發(fā)生在PACU的一個常見并發(fā)癥。3Severallargedatabasestudieshaveshownanassociationbetweenneuromuscularblockingagent(NMBA)useandanincreasedriskofmorbidityandmortalityintheearlyperiodaftersurgery.RecentclinicaltrialshavedemonstratedthatresidualneuromuscularblockinthePACUresultsinairwayobstruction,hypoxemia,andpulmonarycomplicationsduringrecoveryfromgeneralanesthesia.PatientswithresidualblockareatriskforunpleasantsymptomsofmuscleweaknessandprolongedPACUadmissiontimes.Severallargedatabasestudies4很多大樣本數(shù)據(jù)研究顯示肌松藥和術(shù)后早期并發(fā)癥發(fā)生率和死亡率的增高有明顯關(guān)系。最近的臨床試驗也顯示全麻術(shù)后患者在PACU期間的肌松阻滯殘留會導(dǎo)致氣道梗阻、缺氧和呼吸系統(tǒng)并發(fā)癥。有肌松阻滯殘留的患者也面臨肌肉乏力的不適感和PACU停留時間延長的問題很多大樣本數(shù)據(jù)研究顯示肌松藥和術(shù)后早期并發(fā)癥發(fā)生率和死亡率的5Carefulmanagementofneuromuscularblockadeintheoperatingroommayreducetheincidenceofpostoperativeresidualparalysisandthecomplicationsassociatedwithresidualblock.SeveralprinciplesrelatedtoNMBAdosing,monitoring,andreversalhavebeenshowntoreducetheriskofincompleteneuromuscularrecoveryinpostoperativepatients.Theaimofthisreviewistoprovidea“best-availableevidence”assessmentofmethodsthatcanbeusedbyclinicianstoreducetheriskofcomplicationsduetoresidualneuromuscularblockade.Carefulmanagementofneuromus6手術(shù)間內(nèi)對肌松藥使用的認真管理有可能降低術(shù)后肌無力的發(fā)生率和與肌松殘留相關(guān)的并發(fā)癥發(fā)生率。研究表明一些與NMBA劑量、監(jiān)測和拮抗有關(guān)的管理原則可以降低術(shù)后肌松恢復(fù)不完全的風險。這篇綜述的目的是提供一個“好的和可行”的評估方法，從而指導(dǎo)臨床大夫降低與肌松殘留相關(guān)的并發(fā)癥發(fā)生的風險。手術(shù)間內(nèi)對肌松藥使用的認真管理有可能降低術(shù)后肌無力的發(fā)生率和7Q1:Doesqualitativeneuromuscularmonitoringreducetheriskofresidualblock?Asubjective(qualitative)visualortactileassessmentofamuscularresponsetoperipheralnervestimulationisthemostcommonmethodofneuromuscularmonitoringusedintheOR.Pedersenetal.randomized80subjectstoreceiveeitherTOFmonitoringornoneuromuscularmonitoring(clinicalcriteriasuchasbreathingormoving).MedianTOFratiosof0.75and0.79wereobservedinthetwogroupsonarrivaltothePACU(nodifference).

Q1:Doesqualitativeneuromusc8Q1:定性肌松監(jiān)測可以降低肌松殘留的發(fā)生風險嗎？客觀上感知患者對外周神經(jīng)刺激的反應(yīng)是手術(shù)間里最常用的一種肌松監(jiān)測方法。Pedersen等將80名患者隨機分配接受TOF監(jiān)測或非肌松監(jiān)測（臨床標準：呼吸或活動動度）。達到PACU時兩組患者的TOF中位值分別是0.75和0.79，沒有區(qū)別。Q1:定性肌松監(jiān)測可以降低肌松殘留的發(fā)生風險嗎？9AsimilarstudydemonstratedthattheproportionofpatientswithTOFratios<0.7wassignificantlylessinamonitoredgroup(15%)comparedtounmonitoredpatients(47%).Anotherrandomizedtrialdemonstratedthattactileevaluationoftheresponsetodouble-burststimulation(DBS)reduced,butdidnoteliminate,theoccurrenceofresidualparalysis.SignificantlyfewerpatientsinthemonitoredgrouphadTOFratios<0.7(24%)comparedtotheunmonitoredgroup(57%).Asimilarstudydemonstratedt10一項相似的研究顯示：肌松監(jiān)測組患者到達PACU時TOF<0.7的比例（15%）要明顯低于沒有監(jiān)測組（47%）。另一項隨機試驗顯示感覺患者對雙爆發(fā)刺激（DBS）的反應(yīng)可以降低，但不能消除殘留肌松的發(fā)生。有肌松監(jiān)測組的患者TOF<0.7的概率（24%）要低于沒有肌松監(jiān)測組的患者（57%）。一項相似的研究顯示：肌松監(jiān)測組患者到達PACU時TOF<0.11Q2:Does

quantitativeneuromuscularmonitoringreducetheriskofresidualblock?Astudyshowedduring40patients,thereare50%patientsinthenomonitoringhadTOFratios<0.7inthePACU,comparedtoonly5.3%intheAMG(acceleromyograph)group.Aanotherstudyshowedthat17%ofpatientsinthenomonitoringgrouphadresidualblock(definedasaTOF<0.8)comparedtoonly3%intheAMGgroup.Q2:Doesquantitativeneuromusc12Q2:定量肌松監(jiān)測降低肌松殘留的發(fā)生風險嗎？一項研究顯示在40例患者中，在PACU期間在非監(jiān)測組有50%的患者TOF<0.7，而在加速度儀監(jiān)測組只有5.3%的患者TOF<0.7.另一項研究顯示非監(jiān)測組有17%的患者有肌松殘留（定義為TOF<0.8），而加速度儀組只有3%的患者有肌松殘留Q2:定量肌松監(jiān)測降低肌松殘留的發(fā)生風險嗎？13Inthelargeststudy,185patientswererandomizedtoreceiveeitherstandardqualitativemonitoring(peripheralnervestimulator)orAMGmonitoring(TOF-Watch).30%ofpatientsintheformergrouphadaTOFratio<0.9inthePACU,versusonly4.5%intheAMGgroup.在一項大樣本研究中，185例患者被隨機分配為標準定性監(jiān)測（外周神經(jīng)刺激）或者AMG監(jiān)測（TOF-Watch）。前一組中有30%的患者在PACU期間TOF<0.9，而AMG組只有4.5%的患者TOF<0.9Inthelargeststudy,185pati14Q3:Can

neuromuscularmonitoringimpactpostoperativerecovery?Althoughthereisevidencethatqualitativemonitoringcanreducetheriskofpostoperativeresidualblock,atthepresenttimethereisnodatademonstrationthatthistypeofmonitoringimprovesclinicaloutcomes.Incontrast,thereisemergingevidencethatintraoperativequantitativemonitoringcanbeneficiallyimpactpostoperativerecoveryinsurgicalpatients.MortensenetalnotedthatpatientsrandomizedtoreceiveAMGmonitoringhadfewerclinicalsignsofmuscleweaknessinthePACU.Q3:Canneuromuscularmonitorin15Q3:神經(jīng)肌肉監(jiān)測可以反應(yīng)術(shù)后的恢復(fù)情況嗎？雖然有證據(jù)表明定性的監(jiān)測可以降低術(shù)后肌松殘留的風險，不過目前，還是沒有數(shù)據(jù)說明這種監(jiān)測可以改善臨床愈后。與此相反，有證據(jù)提示術(shù)中的肌松定量監(jiān)測對手術(shù)患者的術(shù)后恢復(fù)有一定好處。Mortensen等發(fā)現(xiàn)接受AMG監(jiān)測的患者在PACU期間很少表現(xiàn)出肌肉乏力的臨床征象。Q3:神經(jīng)肌肉監(jiān)測可以反應(yīng)術(shù)后的恢復(fù)情況嗎？16Astudyshowedthatasignificantlyhigherincidenceofhypoxemiaevents(oxygensaturation<90%)andairwayobstructionwasobservedintheperipheralnervestimulatorgroup(21.1%and11.1%)comparedtotheAMGgroup(0%and0%)inPACU.Patients

randomizedtoreceiveAMGmonitoringhadsignificantlyfewersymptomsofmuscleweaknessinthePACUduringthefirst60minutes,andoverallqualityofrecoveryatthetimePACUdischargewassignificantlyimprovedinthesepatients.Astudyshowedthatasignific17一項研究顯示與AMG組（0%和0%）相比，僅接受外周神經(jīng)刺激監(jiān)測的患者在PACU期間發(fā)生低氧血癥（SPO2<90%）和呼吸道梗阻的概率明顯增高。AMG組的患者，在PACU期間的第一小時內(nèi)，肌無力的癥狀較少，從PACU出去時的恢復(fù)質(zhì)量也明顯較高。一項研究顯示與AMG組（0%和0%）相比，僅接受外周神經(jīng)刺激18Q4:Shouldananticholinesterasereversalagentbeadministeredtomostpatientsattheendofsurgery?Anumberofstudieshaveindicatedahighriskofincompleteneuromuscularrecoveryifreversalagentsareomitted.

Caldwelletal.examinedtheincidenceofresidualblock1-4hoursafterasingleintubationdoseofvecuroniumwasgiven,approximatelyone-halfofpatientshadnotachievedaTOFratio>0.9fourhoursaftertheintubationdoseofvecuronium.Q4:Shouldananticholinesteras19Q4:在手術(shù)結(jié)束時應(yīng)該給大多數(shù)患者使用抗膽堿酯酶藥嗎？一些研究提示如果不用抗膽堿酯酶藥，那么肌力恢復(fù)不完全的風險會比較高。Caldwell等觀察了給予單次插管劑量的維庫溴銨后1-4小時的肌松殘留發(fā)生率，在4小時后約一半的患者達不到TOF>0.9的水平。Q4:在手術(shù)結(jié)束時應(yīng)該給大多數(shù)患者使用抗膽堿酯酶藥嗎？20Q5:At

whatTOFcountwillneostigmineproducearapidandreliablereversal?SeveralinvestigationshaveexaminedthetimerequiredtoachieveaTOFratioof0.9orgreaterwhenneostigmineisadministeredatvariouslevelsofneuromuscularblock(TOFcountof1-4withTOFstimulation).Neostigmineshouldnotbeadministereduntilthereissomeevidenceofspontaneousneuromuscularrecovery(shouldnotbegivenataTOFcountof0-theconcentrationofNMBAattheneuromuscularjunctionittoohightocompetitivelyantagonize).Q5:AtwhatTOFcountwillneos21Q5：在TOF計數(shù)多少時新斯的明可以產(chǎn)生比較迅速和可靠的肌松拮抗效果？一些研究觀察了在不同肌松阻滯程度時（TOF刺激儀上TOF計數(shù)從1-4）給予新斯的明到達到TOF0.9或更高值所需的時間。只有當自主呼吸開始恢復(fù)時，才可以給新斯的明（TOF計數(shù)是0時不能給新斯的明，這表明神經(jīng)肌肉接頭的非去極化肌松藥濃度很高，很難被競爭性拮抗）Q5：在TOF計數(shù)多少時新斯的明可以產(chǎn)生比較迅速和可靠的肌松22Kimreversedpatientswithneostigmine(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.Kimreversedpatientswithneo23Kim分別在TOF計數(shù)為1，2，3，4時用新斯的明(70ug/kg)給患者進行拮抗。TOF是1時，TOF達到0.9的平均時間是28.6分鐘(8.8-75.8min)TOF是4時，TOF達到0.9的平均時間是9.5分組(5.1-26.4min)如果在TOF是4時開始拮抗，僅有55%的患者可以在10min內(nèi)TOF值達到>0.9Kim分別在TOF計數(shù)為1，2，3，4時用新斯的明(70ug24KirkegaardetalshowedthatthetimesfromreversaluntilachievingaTOFratioof0.9were20.0(6.5to70.5)minutesataTOFcountof2and16.5(6.5-143.3)minutesataTOFcountof4.Thesestudiesdemonstratethatreversalofneuromuscularblockadeisnotrapidwithneostigmine(requiresapproximately15minutesataTOFcountof4attheendofsurgery).Inaddition,thereislargevariabilityinreversaltimes,evenataTOFcountof4.Kirkegaardetalshowedthatt25Kirkegaard等的研究顯示在TOF值是2和4時，給予拮抗藥到TOF達到0.9，分別需要20min(6.5-70.5)和16.5（6.5-143.3）。這些研究顯示新斯的明的拮抗作用并不快（在手術(shù)結(jié)束TOF是4時，一般需要約15min）。另外，即使TOF計數(shù)為4時才開始拮抗，拮抗肌松作用所需的時間差異也很大。Kirkegaard等的研究顯示在TOF值是2和4時，給予拮26Q6:Areclinicalsignsreliableindicatorsofneuromuscularrecovery?Studiesinawakevolunteersandpostoperativesurgicalpatientshaveexaminedthepredictivevalueofthesetestsindeterminingwhetherfullrecoveryofmusclestrength(TOFratio>0.9)hasoccurred.Theabilitytomaintaina5-secondhead-liftisacommonly-usedtestofmusclerecoveryintheOR.Inastudyinwhich12awakevolunteersweregivenaninfusionofrocuronium,11of12volunteerswereabletomaintaina5-secondhead-liftataTOFratioof0.5.Q6:Areclinicalsignsreliable27Q6：臨床征象是肌松恢復(fù)的可靠指標嗎？在清醒志愿者和術(shù)后患者的一些研究調(diào)查了這些試驗對肌松完全恢復(fù)（TOF>0.9）的預(yù)測價值。OR內(nèi)常用的一個檢測肌松恢復(fù)的試驗是5-秒抬頭試驗在一項對12名清醒志愿者的研究中，給與靜注羅庫溴銨，在12名志愿者中有11名可以在TOF是0.5時完成5-秒抬頭試驗。Q6：臨床征象是肌松恢復(fù)的可靠指標嗎？28Inanotherinvestigation,12awakevolunteersweregivenaninfusionofmivicurium.AtaTOFrationof0.5,allofthevolunteerscouldspeak,openeyesandprotrudetongues,and8ofthe12couldmaintaina5-secondhead-liftandswallow.Inacohortstudy640surgicalpatientswereexaminedtheresidualblock(TOFratio<0.9),noneoftheeightclinicalsignstestsorcombinationsoftest,wereabletoreliabledetectthepresenceofresidualblock.Thesestudiesdemonstratethatclinicalsignsofmusclestrengthareinsensitiveindeterminingthepresenceorabsenceofincompleteneuromuscularrecovery.Inanotherinvestigation,12a29在另一項調(diào)查研究中，12名清醒志愿者被靜注了美維松，在TOF為0.5時，所有的志愿者都可以講話，睜眼和伸舌。12個志愿者里有8名可以完成5-秒抬頭試驗和吞咽。在一項640例手術(shù)患者參與的隊列研究中，對這些患者TOF<0.9的肌松殘留情況的研究發(fā)現(xiàn)，8項臨床征象沒有一個或者幾個聯(lián)合起來可以可靠的發(fā)現(xiàn)肌松的殘留作用。這些研究表明用于判斷肌力的臨床體征并不是神經(jīng)肌肉是否完全恢復(fù)的敏感指標。在另一項調(diào)查研究中，12名清醒志愿者被靜注了美維松，在TOF30Q7:Canresidualneuromuscularblockbereliablyexcludewithconventionalperipheralnervestimulators(qualitativeneuromuscularmonitoring)?Peripheralnervestimulatorsareoftenusedtodeterminedwhetherrecoveryofneuromuscularfunctionhasoccurredattheendofsurgery.IfnofadeisdetectedwithTOF,DBS,ortetanicstimulation,thenrecoveryofmusclestrengthisassumedtobecomplete.Studiesshowedthatcliniciansareunabletousetactileassessmenttoidentifyfadein55%ofcaseswhenTOFratioswerebetween0.4-0.7Q7:Canresidualneuromuscular31Q7：用傳統(tǒng)的外周神經(jīng)刺激器（定性肌松監(jiān)測）是否可以有效的排除肌松阻滯殘余？外周神經(jīng)刺激器通常用來監(jiān)測在手術(shù)結(jié)束時神經(jīng)肌肉功能是否恢復(fù)功能。如果用TOF，DBS或強直刺激沒有發(fā)現(xiàn)肌顫搐衰減，那么認為肌力恢復(fù)完全。研究顯示當TOF在0.4-0.7時，臨床大夫用觸覺的方法難以發(fā)現(xiàn)55%的患者還有肌顫搐的衰減現(xiàn)象。Q7：用傳統(tǒng)的外周神經(jīng)刺激器（定性肌松監(jiān)測）是否可以有效的排32RelativesurveysSurveyshaveconsistentlydemonstratedthatmostcliniciansdonotroutinelymonitorpatientswithperipheralnervestimulatorsintheOR.Asurveyshowedthat24.3%ofeuropeanrespondentsindicatedthatqualitativemonitoringwasnotavailableintheirdepartment,andifsuchmonitoringwasavailable,itwasoftensharedbetween2-3room.Despitehighqualitystudiesdemonstratingabeneficialeffectofquantitativemonitoringontheincidenceofresidualneuromuscularblockade,fewcliniciansroutinelyusethistypeofmonitoring.Relativesurveys33相關(guān)調(diào)查：很多調(diào)查都發(fā)現(xiàn)多數(shù)臨床大夫在OR并不常規(guī)用外周神經(jīng)刺激器監(jiān)測患者。一項調(diào)查顯示有24.3%的歐洲麻醉醫(yī)師指出他們的科室沒有定性肌松監(jiān)測儀，而且，即使有這種儀器，一般也是2-3個手術(shù)間配備一個。雖然研究顯示定量的肌松監(jiān)測對于術(shù)后肌松阻滯殘留的發(fā)現(xiàn)有好處，不過很少有臨床大夫常規(guī)使用這項監(jiān)測。相關(guān)調(diào)查：34Surveyssuggestthatanticholinesterasereversalagentsarenotroutinelyusedbyanesthesiologists.InthesurveybyNaguib,only18%ofEuropeanrespondentsand34%ofunitedstatesrespondentsnotedthattheyalwaysusedananticholinesteraseagentattheendofsurgery.Morethatone-halfoftherespondentsfromtheUSstatedthatrapidandreliablereversalcouldbeachievedataTOFcountof2orless.Furthermore,morethanone-halfoftheeuropeanrespondentsstatedthattheytypicallyallow5minutesorlessbetweenthetimeofneostigmineadministrationandtrachealextubation.Surveyssuggestthatanticholi35調(diào)查發(fā)現(xiàn)麻醉醫(yī)師并沒有常規(guī)用抗膽堿酯酶藥拮抗肌松作用。在Naguib的調(diào)查中，僅18%的歐洲麻醉大夫和34%的美國麻醉大夫提出他們在手術(shù)結(jié)束的時候會常規(guī)用抗膽堿酯酶藥。超過一半的美國麻醉醫(yī)師認為在TOF是2或更低時進行肌松拮抗是可以很快起效，并且拮抗效果滿意。而且超過一般的歐洲麻醉醫(yī)師指出從他們給拮抗藥到拔管的時間通常是5分鐘或者更短。調(diào)查發(fā)現(xiàn)麻醉醫(yī)師并沒有常規(guī)用抗膽堿酯酶藥拮抗肌松作用。在Na36Onthebasisofsurveysthathavebeenpublishedfromaroundtheworld,thereappearstobeasignificantdifferencebetweenpublished“best-evidence”practicesandtheneuromuscularmanagementstrategiesusedbycliniciansindailypractice.基于目前已發(fā)表的調(diào)查，臨床大夫在日常工作中所做的肌松管理和已公布的“最佳證據(jù)”臨床指南之間還有明顯的差別。Onthebasisofsurveysthath37Conclusionsandrecommendations1.tactileevaluationofTOFandDBSfadereduces(butnoteliminate)theincidenceanddegreeofpostoperativeresidualparalysiscomparedwiththeuseofclinicalcriteriatoassessreadinessfortrachealextubation2.Toexcludewithcertaintythepossibilityofresidualparalysisinpatientsatrisk,cliniciansshoulduseobjective(quantitative)neuromuscularmonitoringtests.3.Ideally,neuromuscularfunctionshouldbemonitoredobjectively(quantitatively)inallpatientsreceivingNMBAs.Conclusionsandrecommendation38結(jié)論和推薦1.與用臨床征象來判斷拔管的時間相比，通過對TOF和DBS導(dǎo)致的肌顫搐衰減的觸覺評估可以判斷降低術(shù)后肌松殘留的發(fā)生率。2.為了排除肌松殘留可能的風險，臨床醫(yī)師應(yīng)該進行客觀（定量）的肌松監(jiān)測。