03 Baclofen(不要最后一页)

AlimentPharmacolTher2003;17:243–251.doi:10.1046/j.1365-2036.2003.01394.xBaclofendecreasesacidandnon-acidpost-prandialgastro-oesophagealre uxmeasuredbycombinedmultichannelintraluminalimpedanceandpH

M.F.VELA*,R.TUTUIAN ,P.O.KATZ&D.O.CASTELL 

DepartmentofMedicine,GraduateHospital,Philadelphia,PA,USA;*ClevelandClinicFoundation,Ohio,USA; MedicalUniversityofSouthCarolina,USA

Acceptedforpublication6September2002

SUMMARY

Background:Omeprazolecontrolsacidbutnotnon-acid

re ux.TheGABABagonistbaclofendecreasesacidre ux

throughtheinhibitionoftransientloweroesophageal

sphincterrelaxations(TLESRs)andshouldsimilarly

decreasenon-acidre http://www.77cn.com.cningcombinedmultichannel

intraluminalimpedanceandpH(MII pH),wecompared

acidandnon-acidre uxafterplaceboandbaclofen.

Methods:Ninehealthyvolunteersandnineheartburn

patientsunderwenttwo2-hstudiesofcombinedMII pH

inrightlateraldecubitusafterare uxogenicmealin

randomorder:onplaceboandafterbaclofen40mgp.o.

Tracingswereanalysedforacidandnon-acidre ux

episodes,re-re uxandsymptomsintheheartburn

patients.Results:Innormalsubjectsbaclofensigni cantlyreducedthemediannumberofepisodesofacid(7vs.1,P¼0.02),non-acid(2vs.0,P¼0.005),andallre uxcombined(10vs.2,P¼0.006);re-re uxwasnotreduced(0vs.0,P¼N.S.).Inheartburnpatients,baclofensigni cantlydecreasedthemediannumberofepisodesofacid(15vs.6,P¼0.004),non-acid(4vs.2,P¼0.003),re-re ux(2vs.0,P¼0.02),andallre uxcombined(23vs.8,P¼0.004);italsoreducedthemediannumberofacid-related(9vs.1,P¼0.008)andnon-acid-related(1vs.0,P¼0.04)symptoms.Conclusions:Baclofenreducespost-prandialacidandnon-acidre uxandtheirassociatedsymptoms.GABABagonistsmayhavearoleintreatingGERD.

INTRODUCTION

Whenthecontentsofthestomacharebuffered,as

occursinthepost-prandialperiod,asigni cantpropor-

tionofgastro-oesophagealre uxisnon-acid,and

thereforenotdetectablebyconventionalpH-metry.1–4

Usingcombinedmultichannelintraluminalimpedance

andpHmeasurement(MII pH),wehavepreviously

shownthatalthoughpost-prandialacidre uxis

Correspondenceto:DrM.F.Vela,DepartmentofGastroenterology,Des-

kA 30,ClevelandClinicFoundation,9500EuclidAvenue,Cleveland,OH

44195,USA.

E-mail:velam@http://www.77cn.com.cn

Ó2003BlackwellPublishingLtdmarkedlyreducedafteracidsuppressionwithaprotonpumpinhibitor,non-acidre uxisunaffectedbysuchtreatment;furthermore,moresymptomscanbepro-ducedbythistypeofre ux.1Sincetransientloweroesophagealsphincterrelax-ations(TLESRs)constitutetheprimarymechanismunderlyinggastro-oesophagealacid5–7andnon-acid2re ux,amedicationactingtodecreasethemwouldbeexpectedtoreducebothacidandnon-acidre ux.Adecreaseintransientloweroesophagealsphincterrelaxationshasbeendemonstratedaftertreatmentwithbaclofen8–10andotherGABABagonists11inanimalstudies.IntwostudieswhichevaluatedtheeffectofaGABABagonistonTLESRsinhumans,baclofenwas243

244M.F.VELAetal.

showntoreducetherateofpost-prandialTLESRsand

acidre uxepisodesperhourinhealthyvolunteers12

andpatientswithre uxoesophagitis.13UsingtheBilitec

probe,adecreaseinbilere uxaftertreatmentwith

baclofenhasbeenreportedinabstractform.14Toour

knowledge,quanti cationofnon-acidre uxthrough

MII pHafteradministrationofaGABABagonisthas

notbeencarriedout.

Detectionofre uxofgastriccontentswithapHabove

4.0throughpH-metryisachievablethroughmeasure-

mentofpHfallsofgreaterthanoneunit.However,

pH-metryisunabletodetectthenon-acidre uxthat

occursintheabsenceofpHchanges,whichmay

happenparticularlyinthepost-prandialperiodwhen

thestomachcontentsarebufferedbyameal.Intralu-

minalimpedance,whichbasesthedetectionof uidor

gasintheoesophagusonchangesinelectricalconduc-

tivityacrosspairsofelectrodesplacedwithinthe

oesophageallumen,hasbeenusedasatechniquefor

studyingbolusmovementintheoesophagus.1,2,15,16

WhenthetechniqueiscombinedwithapHelectrode,it

enablesthedetectionofbothacidandnon-acidre ux.17

Combinedmultichannelintraluminalimpedanceand

pHmeasurement(MII pH)hasbeenusedtostudyacid

andnon-acidre uxinadults1,2,18andinfants.19,20

Thedetectionofadditionalre uxepisodesduringan

ongoingacidre uxepisode,i.e.re-re ux,hasbeen

describedinastudyusingcombinedmanometryand

pH-metry.21TheuseofMII pHformeasuring

re-re ux—i.e.impedance-detectedre uxofvolume

whileoesophagealpHisalreadybelow4.0—hasbeen

reportedinabstractform.22Theaimofourstudywasto

usethistechnologytocomparethefrequenciesofpost-

prandialgastro-oesophagealre uxinallitsforms(acid,

non-acidandre-re ux)andassociatedsymptoms,after

treatmentwithplaceboandtheGABABagonist

baclofen.iftheycomplainedofsymptomscompatiblewithheartburn,occurringatleastthreetimesweekly;anendoscopicassessmentwasnotcarriedout.Nursingmothers,subjectswithahistoryofrenalfailure,seizures,neurologicaldisorder,orintolerancetobaclo-fenwereexcludedfromthestudy.Patientswhoweretakingmedicationsalteringintragastricacidityoroesophagealmotilitywereaskedtostoptherapy1weekpriortobeginningthestudy.METHODSThestudyprotocolwasapprovedbytheGraduateHospitalInstitutionalReviewBoard;allsubjectsgavewritteninformedconsent.Ontheinitialvisitaninterviewandphysicalexaminationwereperformed,followedbyoesophagealmanometrytodetermineloweroesophagealsphincter(LES)location.Subjectswhoquali edforthestudyunderwenttwo2-hsessionsofMII pHinrandomorder:onesessionwasperformed1hafterreceivingplacebo,withanothersessiondone1hafterasingleoraldose(40mg)ofbaclofen.Thetwosessionswereperformedatleast48hbutnotmorethan7daysapart.Studieswereperformedintherightlateraldecubitusposition.Subjectsingestedare uxogenicmeal,consistingofasausage-and-eggMcMuf nÒ(300kCal,60%fat)withan8oz(250mL)cupofcoffee,http://www.77cn.com.cnbin …… 此处隐藏：23507字，全部文档内容请下载后查看。喜欢就下载吧 ……