CognitionandBrainStructure

FollowingEarlyChildhoodSurgery

WithAnesthesiaBaryniaBackeljauw

BS,CincinnatiChildren’sHospitalMedicalCenter

兒童期是敏感的神經(jīng)發(fā)育階段，由于麻醉藥能夠強(qiáng)烈的興奮或抑制神經(jīng)傳遞，因此麻醉藥能夠干擾神經(jīng)網(wǎng)絡(luò)發(fā)育，導(dǎo)致長(zhǎng)期功能障礙。在動(dòng)物幼體實(shí)驗(yàn)中發(fā)現(xiàn)，麻醉后會(huì)出現(xiàn)神經(jīng)元缺失和長(zhǎng)期的學(xué)習(xí)、記憶損傷等神經(jīng)認(rèn)知功能受損的情況前言由于小兒特殊的生理和心理特點(diǎn)，麻醉是否會(huì)對(duì)其腦功能有所影響、麻醉藥是否影響其發(fā)育等一直以來(lái)都是麻醉科、兒科和神經(jīng)科醫(yī)生普遍關(guān)注的問(wèn)題。雖然進(jìn)行了大量的研究，許多問(wèn)題尚未清楚。BackgroundAnestheticsinducewidespreadcelldeath,permanentneuronaldeletion,andabstractneurocognitiveimpairmentinimmatureanimals,raisingsubstantialconcernsaboutsimilareffectsoccurringinyoungchildren.BackgroundEpidemiologicstudieshavebeenunabletosufficientlyaddressthisconcern,inpartduetorelianceongroup-administeredachievementtests,inabilitytoassessbrainstructure,andlimitedcontrolforconfounders.MethodsWecomparedhealthyparticipantsofalanguagedevelopmentstudyatage5to18yearswhohadundergonesurgerywithanesthesiabefore4yearsofage(n=53)withunexposedpeers(n=53)whowerematchedforage,gender,handedness,andsocioeconomicstatus.NeurocognitiveassessmentsincludedtheOralandWrittenLanguageScalesandtheWechslerIntelligenceScales(WAIS)orWISC,asappropriateforage.BrainstructuralcomparisonswereconductedbyusingT1-weightedMRIscans.方法ResultsAveragetestscoreswerewithinpopulationnorms,regardlessofsurgicalhistory.However,comparedwithcontrolsubjects,previouslyexposedchildrenscoredsignificantlylowerinlisteningcomprehensionandperformanceIQ.智力聽(tīng)力理解能力ResultsExposuredidnotleadtogrosseliminationofgraymatterinregionspreviouslyidentifiedasvulnerableinanimals.DecreasedperformanceIQandlanguagecomprehension,however,wereassociatedwithlowergraymatterdensityintheoccipitalcortexandcerebellum.ConclusionsThepresentfindingssuggestthatgeneralanesthesiaforasurgicalprocedureinearlychildhoodmaybeassociatedwithlong-termdiminutionoflanguageabilitiesandcognition,aswellasregionalvolumetricalterationsinbrainstructure.ConclusionsAlthoughcausationremainsunresolved,thesefindingsnonethelesswarrantadditionalresearchintothephenomenon’smechanismandmitigatingstrategies.為什么成年人和兒童早期接受麻醉后的影響差異很大？動(dòng)物研究發(fā)現(xiàn)，未完全成熟的小腦神經(jīng)元易受麻醉藥物影響，而小腦結(jié)構(gòu)的損害可能與較低的IQ相關(guān)。討論動(dòng)物實(shí)驗(yàn)證明：全麻藥物可誘發(fā)神經(jīng)細(xì)胞凋亡，最終導(dǎo)致神經(jīng)系統(tǒng)功能損害動(dòng)物研究發(fā)現(xiàn)，未完全成熟的小腦神經(jīng)元易受麻醉藥物影響，而小腦結(jié)構(gòu)的損害可能與較低的IQ相關(guān)。全麻藥觸發(fā)嚙齒類動(dòng)物發(fā)育期大腦的神經(jīng)細(xì)胞凋亡，并致成年期的神經(jīng)功能缺陷，在人類發(fā)育期大腦全麻藥是否也能導(dǎo)致相似的神經(jīng)毒性？

臨床上沒(méi)有足夠臨床資料和流行病學(xué)證據(jù)；麻醉后人腦神經(jīng)元凋亡的組織學(xué)證據(jù)也無(wú)法獲得（在實(shí)踐上和道德上是不可能的）Wilder等和Kallman等回顧性研究認(rèn)為4歲前接受麻醉藥，使用一種以上全麻藥和長(zhǎng)時(shí)間暴露是導(dǎo)致學(xué)習(xí)能力減退的危險(xiǎn)因素，其中2歲前暴露風(fēng)險(xiǎn)較大并不能排除這些神經(jīng)認(rèn)知功能方面的異常是由圍手術(shù)期因素導(dǎo)致的，例如疼痛、炎癥反應(yīng)或一些遺傳相關(guān)的因素。

未能區(qū)分手術(shù)和麻醉各自本身的影響，也不能排除需要手術(shù)的患兒原發(fā)疾病更易發(fā)生學(xué)習(xí)能力減退的可能目前并沒(méi)有排除這些因素的干擾。討論-混雜因素分析發(fā)現(xiàn)，對(duì)于本研究中絕大多數(shù)接受麻醉的孩子，各項(xiàng)量表的評(píng)分不僅在正常范圍內(nèi)，甚至有的還高于總體人群平均水平。因此，如果將這些孩子與總體人群比較，則顯示麻醉并沒(méi)有上述不良影響。討論-統(tǒng)計(jì)學(xué)Ourstudyhasseverallimitations.TheMRIdatausedinthisstudyarebetween8and11yearsold.Morecontemporaryimagingtechniquesmightprovidebetterresolutionandimprovedsensitivitytosubtlebrainvolumetricdifferences.Furthermore,thetimingbetweenthesurgicalprocedureandtheMRIscanandneurocognitiveassessmentvariedfromlessthan2to15yearsaftersurgery,whichcouldhavelimitedtheextentofthedetectablechangesduetobrainplasticityandrepair.Thestudy’ssamplesizewasrelativelysmall,andthetimeintervalsincetheoriginalstudymadeadequatefollow-updifficult.Moreover,studyparticipantswerevolunteeredbytheirparentsfortheinitiallanguageassessmentstudy,whichcouldaffectgeneralizabilityoftheresultstoabroaderpopulationbutdidnotinfluencethecomparisonsbetweenthe2studygroups,whichweredrawnfromthesamecohort.Astypicalforsurgeryininfantsandtoddlers,manychildreninourstudyunderwentsurgeryforchronicearinfections,whichcouldpotentiallyhaveinfluencedlanguagedevelopmentduetohearingimpairmentConcernsforneurobehavioraldisordersandabnormalitiesinbrainfunctioncausedbyenvironmentalchemicalexposureduringearlybraindevelopmenthaverecentlybeenextendedtoanestheticsandsedatives,whichareadministeredtomillionsofyoungchildrenworldwide.1,16

Manysurgicalproceduresearlyinlifetreatlife-threateningconditions,avertserioushealthcomplications,orimprovequalityoflifeandthereforecannotbeeasilypostponedoravoided.Neurotoxiceffectsofallcommonlyusedanestheticsandsedativeshavenowbeenfoundinawidevarietyofanimalspecies,andpostexposurelearningimpairmentshavebeendocumentedinrodentsandnonhumanprimates.8,17Accordingly,thepresentstudyassessedtheeffectsofearlychildhoodanesthesiaforsurgeryonlong-termcognitivefunctionandbrainstructurebycomparingpreviouslyexposedchildren,whoseanesthesiarecordswerereviewed,versusmatchedunexposedcontrolsubjectstolimitconfoundingofcognitiveperformanceandstr