Nonacid GERD.docx

Nonacid GERD.docx

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NonacidGERD

TransAmClinClimatolAssoc.2005;116:

321–334.

Non-acidGastroesophagealReflux:

DocumentingitsRelationshiptoSymptomsUsingMultichannelIntraluminalImpedance（MII）

DonaldOCastell,InderMainie,andRaduTutuian

FromtheDivisionofGastroenterology—Hepatology,MedicalUniversityofSouthCarolina,Charleston,SC

Correspondingauthor:

DonaldO.Castell,MD,DivisionofGastroenterology/Hepatology,MedicalUniversityofSouthCarolina,96JonathanLucasStreet,210CSB,Charleston,SC29425,Phone:

（843）792-7522,Fax:

（843）792-8593,Email:

Castell@musc.edu

Abstract

Multichannelintraluminalimpedance（MII）isanewtechniqueforevaluatingesophagealfunctionandgastroesophagealreflux.Thistechniquedependsonchangesinresistancetoalternatingcurrentbetweentwometalelectrodesproducedbythepresenceofliquidorgasbolusinsidetheesophageallumen.Combinedmultichannelintraluminalimpedanceandmanometry（MII-EM）providessimultaneousinformationonintraluminalpressurechangesandbolusmovementwhereascombinedmultichannelintraluminalimpedanceandpH（MII-pH）allowsdetectionofgastroesophagealreflux（GER）episodesirrespectiveoftheirpHvalues（i.e.acidandnon-acidreflux）.

CombinedMII-pHtestingpresentsanewparadigmforrefluxtesting.InMII-pHstudiesrefluxeventsarenolongerprimarilydetectedbypH.Refluxatepresence,distributionandclearingisprimarilydetectedbyMIIandsimplycharacterizedasacidornon-acidbasedonpHchangeandasliquid,gasormixedbasedonMII.MIIdeterminesrefluxateclearancetimewhilepHmeasuresacidclearancetime.MII-pHshowspromisetobecomeanimportantclinicaltool,particularlytoassessGERinthepostprandialperiodandinpatientswithpersistentsymptomsonacidsuppressiontherapy.

KeyWords:

multichannelintraluminalimpedance（MII）,acidandnon-acidgastroesophagealreflux,gastroesophagealrefluxtesting

Introduction

Multichannelintraluminalimpedanceisanewtechniqueforevaluatingesophagealfunctionandgastroesophagealreflux.Esophagealfunctiontestingisanimportantstepinevaluatingpatientswithpossibleesophagealsymptoms.Thisiscurrentlyperformedusingacombinationofesophagealmanometryandbariumorradioisotopeesophagram.Thecurrent“goldstandard”forgastroesophagealreflux（GER）testingisambulatorypH-metry,amethodbasedondetectionofchangesinacidcontentintheesophageallumen.EventhoughthepathophysiologicroleofacidinproducingGERlesionshasbeenwellestablishedbyanumberofstudiesinbothanimalsandhumans

（1）,GER-typesymptomsoftenpersistdespitetreatmentwithmedicationsthatdecreasegastricacidsecretion.IthasbeensuggestedthatthesesymptomsmaybeduetorefluxhavingpH≥4.0（i.e.non-acidreflux）

（2）,atypeofrefluxthatisdifficulttoidentifywithconventionalpH-metry.

ThisreviewwilldiscussprinciplesofimpedancetestingandtheuseofcombinedmultichannelintraluminalimpedanceandpH（MII-pH）tomonitorgastroesophagealreflux.

BasicPrinciplesofImpedanceTesting

Theprinciplesofthistechniquewerefirstdescribed1990bySilnyetal.（3）anddependonchangesinresistancetoalternatingcurrent（i.e.impedance）betweentwometalelectrodes（i.e.impedancemeasuringsegment）producedbythepresenceofbolusinsidetheesophageallumen.Electricconductivity（theoppositeofresistanceorimpedance）isdirectlyrelatedtotheionicconcentrationoftheintraluminalcontent.Intraluminalcontentwithhighionicconcentrations（i.e.refluxate,food）havearelativelowresistance（highconductivity）comparedtotheesophagealliningorair.Simultaneousvideo-fluoroscopicandimpedancemeasurementsofesophagealfunctionduringswallowinghavevalidatedtypicalchangesobservedwithbolusentry,presenceandclearingintheimpedance-measuringsegment（Figure1

）（3,4）.Intheabsenceofbolus,impedanceisdeterminedbytheelectricconductivityoftheesophageallining.Uponarrivalofbolusbetweentheelectrodesimpedancewilloftenriseabruptlyduetothepresenceofairinfrontoftheheadofthebolus.Intraluminalimpedancethenrapidlydecreasesashighioniccontentofthebolusprovidesgoodelectricconductivity.Whilethebolusispresentintheimpedancemeasuringsegmentintraluminalimpedanceremainslow.Esophagealcontractionsclearingtheintraluminalcontentincreasetheimpedancewithaslight“overshoot”duetoadecreaseinesophagealcross-sectionduringcontractionbeforereturningtobaseline.

Fig.1

Impedancechangesobservedduringbolustransitoverasinglepairofmeasurementringsseparatedby2cm.Arapidraiseinresistanceisnotedwhenairtravelinginfrontofthebolusheadreachestheimpedancemeasuringsegmentfollowedbyadropin（more...）

Multipleimpedancemeasuringsegmentswithintheesophagusallowdeterminationofdirectionofbolusmovementwithintheesophagus;i.e.multichannelintraluminalimpedanceorMII（Figure2

）.Antegradebolusmovement（i.e.swallows）isdetectedbyimpedancechangesduetobolusprogressingproximaltodistal（Figure3

）.Retrogradebolusmovement（i.e.reflux）isdetectedbychangesinimpedanceprogressingdistaltoproximalfollowedbyproximaltodistalclearanceofbolusbyeitheraprimaryorsecondarycontractionwave（Figure4

）.

Fig.2

Multipleimpedancemeasuringsegmentswithintheesophagusallowdeterminationofdirectionofbolusmovementwithintheesophagus;i.e.multichannelintraluminalimpedanceorMII.

Fig.3

Antegrade（i.e.swallows）bolusmovementdetectedbyimpedancechangesofboluspresenceprogressingproximaltodistal.

Fig.4

CombinedMII-EMtracinginwhichretrogradebolusmovementisdetectedbychangesinimpedance（MII）progressingdistaltoproximalfollowedbyproximaltodistalclearanceofbolusacontractionwave.

TheabilityofmultichannelintraluminalimpedancetodetectintraesophagealbolusmovementbychangesinelectricresistanceaswellasmountingoftheimpedancemeasuringsegmentsonstandardmanometryorpHcathetersallowsMIItocomplementtraditionalmanometryorpHtesting.Combinedmultichannelintraluminalimpedanceandmanometry（MII-EM）willnotbediscussedinthismanuscript.Rather,wewillreviewtheconceptofcombinedmultichannelintraluminalimpedanceandpH（MII-pH）todetectGERepisodesofbothacidandnon-acidrefluxtypeandwilldiscusstheevolvinginformationontheadvancesindiagnosisofpotentialGERsymptomsthatthistechnologybringsintotheclinicalarena.

GastroesophagealRefluxMonitoringUsingCombinedMultichannelIntraluminalImpedanceandpH（MII-pH）

ThecurrentlyacceptedgoldstandardfortheassessmentofgastroesophagealrefluxisdistalesophagealpHrecording（5）,whichbasesdetectionofrefluxofacidicmaterialintotheesophagusonchangesinhydrogenionconcentration.ConventionalpHrecordinghasdifficultiesdetectingnon-acidrefluxalthoughsomeauthorshaveproposedthatrefluxcanbedetectedbypHmetryevenwhenintraesophagealpHremainsabove4.0butshowadefinitefallgreaterthatonepHunit（6）.Currentlyavailabletechniquesforthestudyofnonacidoralkalinerefluxhaveseverallimitations:

aspirationtechniques（7）allowforonlyshortanalysisperiodsandtheaccuracyofenzymaticdeterminationofthecontentsoftheaspirateshasbeenquestioned（8）,scintigraphicmethods（9,10）areexpensive,involveradiationexposureandarelimitedtoshortmonitoringperiods,ambulatorycombinedpHmonitoringandbilirubinmonitoring（Bilitec®）（11）requiresthepresenceofbilirubinandisthereforeincapableofmeasuringbile-freenonacidrefluxwhichaccountsfor≥90%ofnon-acidreflux（12）.FurthermoretheBilitecdevicerequiresspecialliquiddietsduringthemonitoringperiodtoavoidfalsepositivereadings（13）.

MultichannelintraluminalimpedanceusedincombinationwithpHmetry（MII-pH）hasbeenshowntoallowaccuraterecordingofgastroesophagealrefluxatallpHlevelsandisemergingasausefultooltostudybothacidandnonacidreflux（14,15）.Thetechniquehasbeenvalidatedfluoroscopicallyandmanometricallytodetectbolusmovementintheesophagusbothintheoralandaboraldirection（16）,andthusenablesmeasurementofanddistinctionbetweenswallowsandreflux.BecauseMIIrecordsretrogradeflowofgastriccontentsintotheesophagusinapH-independentfashion,combiningthetechniquewithpHmetryenablesdetectionofnonacidaswellasacidreflux.Additionally,MII-pHprovidesdetailedcharacterizationoftherefluxepisode,includingdeterminationofthecomposition（gas,liquidormixed）andtheheightreachedbytherefluxate（17–19）.

CombinedMII-pHequipment

ThecombinedMII-pHcatheterissimilartoastandard2-mmflexiblepH-catheter.The“classic”6MII-1pHassembly（Figure5

）hasfourimpedancemeasuringsites（Z1–Z4）inthedistalesophagusandtwoimpedancemeasuringsitesintheproximalesophagus（Z5–Z6）.ThepHsensoronthisassemblyisatthesamelevelasthecenterofthesecondimpedance-measuringsegment.ThecatheterisplacedtransnasallyintotheesophagusandpositionedsothatthepHsensorislocated5cmabovetheproximalborderoftheloweresophagealsphincter（LES）.ManystudiesnowincorporateasecondpHsensorlocated15cmmoredistalonthecathetertorecordpHinthegastricfundus.Theimpedancemeasuringsegmentswillbelocatedat3cm,5cm,7cmand9cmabovetheLESinthedistalesophagusandat15cmand17cmabovetheLESintheproximalesophagus.InitialstudiesusingMII-pHweredonewithstationaryset-upsandoverrelativelyshortperiodsoftime（2to3hourrecordingsessions）.Morerecently,equipmenttoperformambulatoryMII-pHstudi