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1、REVIEWARTICLEDavidC.Warltier,M.D.,Ph.D.,EditorAnesthesiology2007;107:14452Copyright©2007,theAmericanSocietyofAnesthesiologists,Inc.LippincottWilliams&Wilkins,Inc.AdvancesinandLimitationsofUp-and-downMethodologyAPre´cisofClinicalUse,StudyDesign,andDoseEstimatio
2、ninAnesthesiaResearchNathanL.Pace,M.D.,M.Stat.,*MarioP.Stylianou,Ph.D.Sequentialdesignmethodsforbinaryresponsevariablesofthepatientcanbeobservedimmediately.1Theearliestexistfordeterminationoftheconcentrationordoseassociatedusebytheanesthesiaresearchcommunityofo
3、nepartic-withthe50%pointalongthedoseresponsecurve;theup-and-ularsequentialdesigntheup-and-downmethoddownmethodofDixonandMoodisnowcommonlyusedinanesthesiaresearch.Therehavebeenimportantdevelopments(UDM)seemstohavebeeninstudiesoftheeffectiveinstatisticalmethodsth
4、at(1)allowthedesignofexperimentsconcentrationfora50%response(EC50orminimumforthemeasurementoftheresponseatanypoint(quantile)alveolarconcentration)ofinhalationanesthestics.2,3alongthedoseresponsecurve,(2)demonstratetheriskofColumbandLyons4usedthesamedesignandrep
5、ortedcertainstatisticalmethodscommonlyusedinliteraturereports,theEC50labeledbythemtheminimumlocalanalgesic(3)allowtheestimationoftheconcentrationordosethetar-getdoseassociatedwiththechosenquantilewithouttheas-concentration(MLAC)ofepiduralbupivacaineandli-sumpti
6、onofthesymmetryofthetolerancedistribution,and(4)docaineforpainreliefduringlabor.Theuseofthissetboundsontheprobabilityofresponseatthistargetdose.experimentaldesignisnowcommonlyseeninstudiesofThisarticledetailsthesedevelopments,brieflysurveyscurrentintrathecalloca
7、lanesthestics,5intrathecalopioids,6intra-useoftheup-and-downmethodinanesthesiaresearch,reana-78venousopioids,intravenous2agonists,intravenouslyzespublishedreportsusingtheup-and-downmethodforthe910studyoftheepiduralreliefofpainduringlabor,anddiscussesanesthetic
8、s,andinhalationanestheticsallstudiesde-appropriateinferencesfromup-and-downmethodstudies.terminingtheconcentrationordose(EC50orED50)ofthesedrugs.ADRUGtolerancedistributionis
