bells palsy a clinical practice guideline for：貝爾麻痹的臨床實踐指南

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AClinicalPracticeGuidelinefortheManagementofBell’sPalsy

JohnR.deAlmeida,MD,MSc,FRCSC

GordonH.Guyatt,MD,MSc,FRCPC

SachinSud,MD,MSc,FRCSC

JoanneDorion,PT,BScPT

MichaelD.Hill,MD,FRCPC

MichaelR.Kolber,MD,MSc,CCFP

JaneLea,MD,FRCSC

SylviaLoong,RegPT

BalvinderK.Somogyi,BSW

BrianD.Westerberg,MD,FRCSC

ChrisWhite,MD,FRCPC

JosephM.Chen,MD,FRCSC

Introduction

Bell’spalsyisanacuteonsetidiopathicweaknessorparalysisofthefaceofperipheralnerveorigin.Otherperipheralcausesoffacialweaknessorparalysisincludeinflammationoftheearortemporalbone(otitismedia,mastoiditis,cholesteatoma),viralinfections(herpeszosteroticusorRamsayHuntsyndrome,Lymedisease),granulomatousdiseases(sarcoidosis,Melkersson-Rosenthalsyndrome),andneoplasmsofthecerebellopontineangle,temporalbone,orparotidgland.

Bell’spalsyaffects20-30personsper100,000onanannualbasisand1in60individualswillbeaffectedoverthecourseoftheirlifetime.1,2Theconditionisresponsibleforalmostthree-quartersofallacutefacialpalsies.1Thereisnogenderpredilection,althoughithasbeenassociatedwithpregnancy.1StudieshavealsosuggestedanassociationbetweenBell’spalsyanddiabetes.3,4Certainvaccinationshavealsobeenassociatedwiththedevelopmentofthisconditionincludinganintranasalinfluenzavaccine5andaSwedishinfluenzaH1N1vaccine.6Todate,therehasbeennoassociationwithNorthAmericanvaccines.7,8

Roughly75%ofpatientswithBell’spalsybelievetheyarehavingastroke.9Fortheclinician,itisimportanttodifferentiateperipheralfromcentralcausesforfacialweakness.Patientswithperipheral(lowermotorneuron)facialnervepalsiesdemonstrateweaknessofboththeupperandlowerhalfoftheface.However,duetouppermotorneuroninnervationfrombothcerebralhemispheres,centralfacialnervepalsiesdemonstrateparesisorparalysisonlyonthelowerquadrantofthefacewithsparingofeyeclosureandforeheadwrinklemovements.1,3,10

ThemajoretiologyofBell’spalsyisbelievedtobeaviralinfectionofthefacialnervebytheherpessimplexvirus.11-13Inonestudy,herpesvirusDNAwasidentifiedintheendoneurialfluidatthetimeofsurgicaldecompressionofthenerve.14Asaresultofthisviralinfectionthefacialnerveswellsandiscompressedinitscanalasitcoursesthroughthetemporalbonecausinganischemicinjurytothenerve.

Indevelopmentoftheseguidelines,anumberofprognosticfactorswereconsideredtoberelevant.ClassifyingBell’spalsyaccordingtotheseverityofweaknessprovidesprognosticinformationthatmayguidetreatment.ThemajorityofBell’spalsypatients(70%)haveacompletefacialparalysis,while30%havepartialweaknessorparesis.15ThereareseveralinstrumentsavailabletoquantifytheseverityofBell’spalsy.15TheHouse-Brackmann(Table1)andSunnybrookscalesarethemostcommonlyusedinstruments.16,17Thesevalidatedinstrumentsobjectivelygradetheextentoffacialmuscleparesisallowtreatingclinicianstomonitorpatientsandtocounselthemregardingthelikelihoodofrecovery.Patientswithmildtomoderateparesis(theequivalentofHouse-BrackmanngradesII-IV)havebetterratesofrecoverythanthosewithseveretocompleteparesis(House-BrackmanngradesV-VI).18Inalargesingle-institutioncohortstudy,recoveryratesof61%and94%weredocumentedinpatientswithcompleteandincompleteparalysisrespectively.19

Electroneuronography(ENoG)mayalsoprovideadditionalprognosticinformation.Thiselectricalstimulationtestcomparestheaffectedorparalyzedsidetotheunaffectedside.Inonestudy,only42%ofpatientswithagreaterthan90%degenerationofthefacialnervefunctiononaffectedsidehadagoodrecovery(HouseBrackmanngrade1or2).20Historically,ENoGhasbeenusedtoselectpatientswithapoorprognosiswhomaybecandidatesforsurgicaldecompressionofthefacialnerve.

OtherimportantclinicaloutcomesexistinBell’spalsy.Upto16%willhaveresidualinvoluntarymovementsand/orsynkinesis,15whileothersmayhaveabnormallacrimationwithsalivation(crocodiletears).Failuretoprotectthecorneaamongpatientswhoareunabletoblinkadequatelymayresultincornealulcerationandpermanentvisualimpairment.Thosewithresidualdeficitsmayhavealong-termreducedqualityoflifeandpsychologicaldistress.4,21,22

PreviousguidelineshavemaderecommendationsforthetreatmentofBell’spalsy.AQualityStandardsSubcommitteeoftheAmericanAcademyofNeurologyissuedapracticeparameterin2001concludingthattherewasnotsufficientevidencetosupporttheuseofcorticosteroids,antiviralagents,orsurgicaldecompressionforBell’spalsy.23Arecentupdateofthisguideline,however,advocatedtheuseofcortisteroidsandconcludedthatantiviralsmaybeofmodestbeneft.24Oftwoothertreatmentguidelines,oneconcludedthattherewasinsufficientevidencetogivecorticosteroidsinchildren25andtheothersuggesteduseofcorticosteroidsbasedonanarrativereviewoftheavailableevidence.26Recentsystematicreviewsforexerciseandelectrostimulationphysiotherapy27aswellassurgicaldecompression23haveprovidedfurtherinsight.ThisgrowingbodyofliteraturewastheimpetusfordevelopingguidelinesforthetreatmentofBell’spalsy.ThisguidelinewillreviewtheevidenceforthemedicaltreatmentofBell’spalsywithcorticosteroidsandantivirals,facialexerciseandelectrostimulationphysiotherapy,decompressionsurgery,theneedforeyeprotectivemeasures,andtheneedforfurtherinvestigationandspecialistreferralinpersistingandprogressivecases.RecommendationsweremadeusingtheGradingofRecommendationsAssessment,DevelopmentandEvaluation(GRADE)systemforthedevelopmentofclinicalpracticeguidelinerecommendations.28-31Becauseoftheimportantprognosticimplicationsofinitialseverityofparesis/paralysis,thisguidelinepanelmadeseparaterecommendationsbasedthedegreeoffacialweaknessatpresentation(mildtomoderateparesisversusseveretocompleteparesis).ThisguidelineisaimedatallhealthcareproviderswhotreatBell’spalsy.

Methods

SelectionandOrganizationofthePanel

Aworkinggroupofelevenmemberswasassembledundertheauspicesof(insertendorsing{Pendingapprovalfromendorsingorganizations)

organizations-possiblyCanadianSocietyofOtolaryngologyandCanadianNeurologicalSciencesFederation).Thegroupconsistedofthreemethodologists(JDA,SS,GG),threeOtolaryngology-HeadandNeckSurgeons(JDA,JC,BDW),twoNeurologists(MDH,CW),oneFamilyPhysician(MK),twoFacialNerveTherapists(JD,SL),andonepatient(BKS).Anadditionalmethodologist(JL)wasinvolvedinthereviewprocess,butnottheguidelinerecommendations.PanelistswereselectedbasedonademonstratedacademicinterestinBell’spalsyand/orbyrecommendationofrelevantnationalsocieties.Thepatientpanelmemberwasselectedbyinvitationfromoneofthepanelists.GuidelinesweredevelopedthroughaseriesoffourconferencecallsandmultipleemailcorrespondencesbetweenJanuary,2010andJune,2012.GGchairedthepanelandJDAwasinchargeoforganizationalaspectsoftheprocess.

DefiningtheClinicalQuestionsandImportantOutcomes

ContentexpertsinthepanelincludingtheOtolaryngology-HeadandNeckSurgeons,Neurologists,FamilyPhysician,andFacialTherapistswereinvolvedindraftingalistofclinicalquestionsandsubjecttopicstobeaddressedbytheguideline(Table2).Theworkinggroupidentifiedoutcomesdeemedimportanttopatientsattheoutsetoftheguidelinedevelopmentprocess(Table3).Eachoutcomewasratedbyeachpanelmemberonascalefrom1-9assuggestedbytheGRADEworkinggroup.29Inmakingratings,panelistswereinstructedto,onthebasisoftheirpersonalorclinicalexperience,totaketheperspectiveofapatientwhohasBell’spalsy.Scoresfrom1-3wereclassifiedasnotimportant,scoresfrom4-6wereclassifiedasimportantbutnotcritical,scoresfrom7-9wereclassifiedascritical.Evidenceforoutcomeswereevaluatedbysystematicreviewandthenusedinmakingrecommendations.Theprimaryoutcomeforthisanalysisisunsatisfactoryfacialmotorrecovery(House-Brackmannscoreofgrade3-6orequivalent).Althoughotherfacialoutcomessuchassynkinesisandautonomicdysfunctionmaybeconsideredunsatisfactoryrecovery,wehavedefinedtheseasseparateoutcomesfromtheprimaryoutcome.

DataCollection,Synthesis,andMeta-analysis

RelevantsystematicreviewswereidentifiedforeachclinicalquestionbysearchingonPubMed/MEDLINEthroughJanuary2011.Allidentifiedsystematicreviewswerepresentedtothegroupinsummaryformatincludingnumberofincludedstudies,numberofpatients,outcomesconsidered,relevantfindingsandmethodologiclimitations.Onesystematicreviewforeachsubjectareawasselected.Reviewswereselectedbasedonmethodologicquality,numberofstudiesincluded,andmostrecentlypublished.Forsubjectareasinwhichnosystematicreviewwasavailable,newreviewswereconducted.Updatedreviewswereperformedforreviewspublishedmorethan2yearspriortothestartoftheguidelinedevelopmentprocess.

Previoussystematicreviewswerechosenbythegroupfortheuseofcorticosteroid,antiviralagent,andcombinedtreatment(recommendations1-6);32theuseofexercisephysiotherapyandelectrostimulationphysiotherapy(recommendations7-9);27andtheuseofsurgicaldecompresssioninthetreatmentofBell’spalsy(recommendation10).23UpdatestothesesystematicreviewswereperformedusingthesamesearchstrategyanddataextractionandsynthesismethodsasdefinedintheprimaryreviewandincludedstudiesuptoJanuary2011.Newsystematicreviewsofrandomizedcontrolledtrialsorobservationalstudieswereconductedforeyeprotectivemeasures(recommendation11),specialistreferral(recommendation12),investigationformalignancy(recommendation13),valuesandpreferences,andcost-resourceuse.

ThesearchesfornewstudiesincludedMEDLINE,EMBASE,CENTRAL,PsychInfo,CINAHL,andthroughJanuary2011.Bibliographiesofrelevantarticleswerealsosearched.IncludedstudiesforallreviewswereRCT’swiththeexceptionofthesurgicaldecompressionreview,asRCT’sforsurgicaldecompressionwereunavailable.Forrecommendations11-13wedidnotidentifyanyrandomizedcontrolledstudiesorobservationalstudies.Intheabsenceofevidencefromrandomizedcontrolledtrialsorobservationalstudies,recommendationswerebasedonpanelists’personalexperience.

Forneworupdatedreviews,tworeviewers(2ofJDA,CW,JL,SS)screenedallstudiesforeligibilityandextracteddata.Disagreementswereresolvedbyconsensus.Foreachreview,thesetting,patienteligibility,numberofpatients,treatmentineacharm,andoutcomesconsideredineachstudywasrecorded,anddatawasgatheredforeachofthechosenoutcomes.RiskofbiaswasassessedusingCochranesystematicreviewguidelines,whichassessadequacyofrandomsequencegeneration,allocationconcealment,blinding,losstofollow-up,selectivereporting,orotherbiases.33Meta-analyseswereconductedusingRevManSoftware(version5.0).HeterogeneitywasassessedusingtheI2statistic.

Foreachtreatmentorintervention,wecreatedsummarytablessummarizingtheavailableevidenceassuggestedbytheGRADEworkinggroup.29Thesesummarytablesincludedinformationforallidentifieddesirableandundesirableoutcomes.Foreachoutcome,werecordedthenumberofstudies,numberofpatients,evidenceratings,relativeriskwithtreatment,baselinerisk,interventiongrouprisk,numberneededtotreat,qualityofevidence,andoutcomeimportance.

EvaluatingConfidenceinEffectEstimates(QualityofEvidence)

ConfidenceineffectestimateswasassessedbasedonguidelinessuggestedbytheGRADEworkinggroup.29Inshort,theGRADEgroupsuggeststhattheconfidenceineffectestimatesforanyoutcomecanbegivenoneoffourgrades(verylow,low,moderate,orhigh).Factorsthatcandecreasetheconfidenceineffectestimateincluderiskofbias,inconsistencyofresults,indirectnessofevidence,imprecision,andpublicationbias.Factorsthatincreasetheconfidenceinaneffectestimateincludealargemagnitudeofeffect,plausibleconfoundingthatwouldreduceademonstratedeffect,andadose-responsegradient.Theoverallconfidenceforanygivenrecommendationisbasedonevaluatingtheconfidenceineffectestimatesforalltheoutcomesofinterest.Weratedtheoverallconfidenceacrossalloftheseoutcomesasthelowestconfidenceofeffectestimateforanycriticaloutcome.

MakingRecommendations(GRADE)

RecommendationsweremadeusingtheGRADEsystem28-31whichcategorizesrecommendationsasstrongorweak.Thestrengthofrecommendationsarebasedonfourfactors:28thebalanceofdesirableandundesirableconsequences,theconfidenceineffectestimateforeachofthecriticalandimportantoutcomes,29variabilityinpatientvaluesandpreferencesandresourceuse.31

Recommendationsweremadebasedonnominalgrouptechniqueswherebythegroupmembersmetbyconferencecall,voicedtheiropinions,andreflectedontheopinionsofothers.Attheendofthediscussionandafterconsideringtheabovefourfactors,thegroupmadeaconsensusrecommendation—eitherstrongorweakinfavouroragainstornorecommendation.Whenconsensuswaselusive(recommendations5and7),therecommendationsweresubmittedtoablindvoteandrecommendationswerebasedonaprocesspreviouslydescribed.34Eachworkinggroupmembervotedinoneoffivecategories(stronginfavor,weakinfavor,norecommendation,weakagainst,strongagainst).Forarecommendationtobeinfavouratleast50%ofgroupmemberswererequiredtovoteinfavour,withnomorethan20%votingagainst.Forarecommendationtobestrongrecommendation,atleast70%ofthegroupwererequiredtoendorseitasastrongrecommendation.

ConflictsofInterest

Groupmembersdisclosedfinancialandintellectualconflictsofinterest(AppendixA:COIDeclarationForm)).Eachpotentialconflictofinterest(COI)wasevaluatedtodeterminewhethertheCOIwasacceptableorunacceptable.Thefollowingcriteriaweredeterminedaprioriandservedasexclusioncriteriafrompanelinvolvement.

Significantequityholdingincompanyrelatedtothesubjectmatteroftheguidelines

Significantincomeoriginatingfromacompanyrelatedtothesubjectmatteroftheguidelines

Refusaltoavoidfinancialinvolvementinindustriestiedtotherapiesforwhichrecommendationswillbemadeforaperiodofayearfollowingthedevelopmentoftheguidelines.

FourpanelmembersweredeterminedtohaveimportantbutacceptableCOI’s.Threemembers(JDA,GG,JC)hadanintellectualCOIwiththerecommendationsforantiviralandcorticosteroidtherapyastheyhadpreviouslypublishedonthistopic.Onemember(SL)hadafinancialCOIonthetopicofexercisephysiotherapyassheiscurrentlyinvolvedinthedeliveryofthisserviceinprivatepractice.Theseindividualswerepermittedtoparticipateincollectingandinterpretingevidence,butwerenotinvolvedinthedeliberationforrecommendationsforwhichtheywereconflicted.35

Implementation

Implementationoftheseguidelineswillbeginwithpublicationofthecompletedmanuscript,whichwillfacilitatewidedistribution.Endorsingorganizationswillbeaskedtomakeacopyoftheguidelinesavailabletophysicianandotherhealth-caremembers.Toaidinutilizationoftheseguidelines,allpertinenthealth-carestakeholdershavebeeninvolvedintheguidelinemakingprocessandrelevantprofessionalorganizationshavebeeninvitedtoreviewand/orendorsetheguideline.

RecommendationsandRationale

1)CorticosteroidtreatmentforacuteBell’spalsyofanyseverity.

InpatientswithacuteBell’spalsyofanyseverity,werecommendtheuseofcorticosteroids.(StrongRecommendation:ModerateConfidenceinEffectEstimate)

Systematicreviewoftheliteratureyieldedtenstudiescomparingcorticosteroidstoplaceboincluding1285patients(Table4,5,6).36-46Wehadmoderateconfidenceineffectestimatebecauseofimprecisionineffectestimates.Meta-analysisofthesestudiesdemonstratedarelativerisk(RR)of0.69(95%CI,0.55-0.87)ofunsatisfactoryfacialrecovery.32Inthepreviouslypublishedmeta-analysis,32asubgroupanalysiswaspresentedformildtomoderateparesis(3studies)36,41,42versusseveretocomplete(4studies)36,41,42,43paralysis.Statisticalanalysisdidnotshowastatisticallysignificantsteroidsubgroupeffect(i.e.nodifferenceinrelativeriskinthetwogroups),eitherduetoasubgroupeffectnotbeingpresent,orduetoinsufficientpowertoshowaneffect.32WethereforeappliedthesameRR(0.69;95%CI,0.55–0.87)forbothmildtomoderateparesisandseveretocompleteparalysisatpresentation.

Theestimatedriskofincompleterecoverywithouttreatmentforpatientswithmildtomoderateparesiswas6per10019andacorrespondingriskwithtreatmentof4per100(95%CI,3-5)resultinginanabsoluteriskreductionof2%(95%CI,1-3%)andanumberneededtotreat(NNT)of50(95%CI,33-100).Inpatientswithseveretocompleteparesis,thebaselineriskforincompleterecoveryis39per100.19theriskofunsatisfactoryrecoveryaftertreatmentwithcorticosteroidsis27outof100(95%CI,21–34)resultinginanabsoluteriskreductionof12%inthisgroup(95%CI,5–18%)correspondingtoanNNTof8(95%CI,6–20)(Table6).Threestudieswith671patientsshowedasignificantreductioninsynkinesisandautonomicdysfunction(RR=0.56;95%CI,0.41-0.76),36,40,45withasimilarnumberneededtotreatof8(95%CI,(6–17).

Althoughcorticosteroidshavepotentialcomplications,sevenstudiesinvolving1155patientsshowednoincreaseriskofmajororminorsideeffectsinthosereceivingshorttermtreatmentversuscontrolsubjects.36,37,39,40,41,44,45Therewerenoreportedcasesofavascularnecrosisofthehipinpatientstreatedwithcorticosteroids.Onestudyreported4episodesofgastriculcerationinpatientstreatedwithcorticosteroidsgivenincombinationwithantiviralsandnoepisodesincontrolpatients.47

Thedosingregimensforcorticosteroidswerehighlyvariableinthesystematicreview.Allstudiesusedeitherprednisoneorprednisolonederivatives.Allbutonestudy36usedataperedregimen.Thedurationoftreatmentrangedfrom6to17days,40,45with6studiesusingatendaycourse.36,37,39,41,43,44Subgroupanalysisinthepreviouslypublishedmeta-analysisidentifiedasignificantlybettereffectwithatotaldoseof450mgorhighercomparedtolessthan450mg.32Areasonableregimensuggestedbyfouroftheincludedstudiesinvolvesafivedaycourseof60mgperdayfollowedbyafivedaytaper,reducingthepreviousday’sdoseby10mgperday.37,39,41,44

Thewindowofopportunityfortreatmentwithcorticosteroidsisunclear.Somerecenttrialsonlyincludedpatientstreatedwithin72hoursofsymptomonset.18,37Weperformedsubgroupanalysestoseeifpatientstreatedoutsideofthiswindowhadpoorerrecoveryandwereunabletoshowadifference.32However,arecentsubgroupanalysisofthelargeSwedishrandomizedcontrolledtrial,suggestedthatsteroidsareonlybeneficialifstartedwithinthefirst48hours(p=0.5).48

Thetreatingclinicianshouldexploreforrelativecontraindicationstocorticosteroidtherapysuchasdiabetes,pepticulcerdiseaseandaremotehistoryoftuberculosis.Ifpresent,adiscussionwiththepatient,explainingthepotentialbenefitofcorticosteroidsintreatingBell’spalsyandthepotentialrisksshouldensue.

UsingcorticosteroidsforthetreatmentofBell’spalsyisalsocost-effective.BasedonresourceusedatafromarecentUKcost-effectivenessanalysis,corticosteroidstreatmentdominatedallothertreatmentoptionsincludingplacebo,combinedcorticosteroidsandantiviraltherapy,andantiviralalonetreatment.49Patientsonsteroidsrequiredfeweroutpatientspecialistvisitsandfewervisitstotheprimarycarephysicianthanallothertreatmentarms.I

AntiviralswithoutcorticosteroidsforacuteBell’spalsyofanyseverity.

InpatientspresentingwithacuteBell’sPalsyofanyseverity,werecommendagainstantiviraltreatmentalone.(StrongRecommendation:ModerateConfidenceinEffectEstimate)

Systematicreviewoftheliteratureyieldedtwostudiescomparingantiviralsplusplacebotodoubleplaceboincluding658patients(Table4,5,7).36,37,46Therewerenosignificantstudylimitationsorpublicationbias,theresultswereconsistentanddirect.However,therewassomeimprecisionintheeffectestimates.Meta-analysisofthesestudiesdemonstratednobenefitintherelativeriskofunsatisfactoryrecovery(RR=1.14;95%CI0.8-1.62)forpatientstreatedwithantiviralscomparedtoplacebo.Subgroupanalysisfailedtodetectadifferenceineffectbetweenpatientswithmildtomoderateparesisandthosewithseveretocompleteparalysis.

Majorandminorsideeffectsassociatedwithantiviraltherapywereinfrequent.Oneepisodeofrecurrentatrialfibrillationwasdescribedinapatientwhoreceivedantiviralagents.Meta-analysisoftwostudies(N=653)comparingantiviraltherapytoplacebodidnotshowanincreaseriskofmajororminorsideeffects,althoughwideconfidenceintervalsduetosmallnumbersoftrialsandoutcomeeventsresultedinconsiderableimprecision.36,37

Therewasnosignificantbenefitofantiviraltherapyforsynkinesisandautonomicdysfunction(RR=1.04;95%CI,0.75–1.43,onetrial,N=373);painat9months(AdjustedOddsRatio(OR)=0.05,95%CI-0.91–1.01,onetrial,N=496);36orhealth-relatedqualityoflifeat9months(AdjustedOR)=-0.02,95%CI-0.05-0.01,onetrial,N=496).36

Inastudyofcost-utility,administrationofantiviralswasshowntobemorecostlyandlesseffectivethannotherapysuggestingthatantiviraltreatmentwasdominatedbynotreatment,corticosteroidalone,andcombinedtreatment.49Patientstreatedwithantiviralsalonerequiredmorevisitstotheirgeneralpractitionersandmorespecialistoutpatientappointmentsthanallothertreatmentarmsandthantheplacebogroup.

CombinedCorticosteroid/AntiviraltherapyforAcuteBell’sPalsywithmildtomoderateparesis

ForpatientspresentingwithacuteBell’spalsywithmildtomoderateparesis,wesuggestagainsttheadditionofantiviralstocorticosteroidsforpatients(Weakrecommendation:ModerateConfidenceinEffectEstimate).

Systematicreviewoftheliteratureyielded8studiescomparingcombinedcorticosteroidsandantiviraltherapytocorticosteroidsalonethatincluded1298patients(Table8).36,37,38,46,50-54Theconfidenceineffectestimatewasratedasmoderateduetosomeimprecisionineffectestimates.Meta-analysisofthesestudiesdemonstratedarelativeriskofunsatisfactoryrecoveryof0.75(95%CI,0.56-1.00)forpatientstreatedwithcombinedtherapycomparedtocorticosteroidsalone.Assumingariskofunsatisfactoryfacialrecoveryinpatientswithmildormoderateparesiswithcorticosteroidonlytreatmentof4per100,thecorrespondingriskwithcombinedtreatmentis3per100(95%CI,2-4)resultinginanabsoluteriskreductionof1%(95%CI,0–2%).

Majorandminorsideeffectsassociatedwithaddinganantiviraltocorticosteroidtherapywereinfrequent.Meta-analysisoffourstudies(N=941)comparingantiviraltherapytoplacebodidnotshowanincreaseriskofmajor(RR1.33,95%CI0.26–6.82)orminorsideeffects(RR1.160.81-1.62),althoughwideconfidenceintervalsduetosmallnumbersoftrialsandoutcomeeventsresultedinconsiderableimprecision.36,37,47,50

Inthreestudieswith511patients,therewasareductionintheriskofsynkinesisandautonomicdysfunctionwhenanantiviralwasaddedtocorticosteroid(RR0.59;95%CI0.39-0.89).36,40,45Assumingariskofsynkinesisof15per100inpatientstreatedonlywithcorticosteroids,19thecorrespondingriskwiththeadditionofanantiviralis9per100,withaNNTof17(95%CI20-50).

Thecost-effectivenessanalysiscitedabovealsoaddressedtheadditionofantiviraltherapyandfoundthatcorticosteroidmonotherapywaslesscostlyandmoreeffectivethancombinedtherapy.49Inourmeta-analysisofseveralstudiesincludingthetrialonwhichthiscost-effectivenessstudywasbased,wefoundthecontrary;thattheadditionofantiviralstocorticosteroidsismoreeffectivethancorticosteroidmonotherapy.Thisdifferenceislikelyduetoincreasedstatisticalpowerasaresultofpoolingstudies.

Theweakrecommendationagainsttheuseofantiviralsforpatientswithmildtomoderateparesisplacesrelativelyhighvalueonthelowabsolutereduction(andhighnumberneededtotreat)intheriskofunsatisfactoryrecoveryandrelativelylowvalueonthebenefitofreducedsynkinesis.Patientswithmildtomoderateparesiswhoplacehighervalueonavoidingsynkinesismightconsiderantiviralsinadditiontocorticosteroids.

CombinedCorticosteroid/antiviralforacuteBell’sPalsywithsevereparesistocompleteparalysis

ForpatientswithacuteBell’spalsywithseveretocompleteparesis,wesuggestthecombineduseofantiviralsandcorticosteroids.(WeakRecommendation:ModerateConfidenceinEffectEstimate)

Asinthepreviousrecommendation,meta-analysisdemonstratedarelativeriskofunsatisfactoryrecoveryof0.75(95%CI0.56-1.00)forpatientstreatedwithcombinedtherapycomparedtocorticosteroidsalone.32However,inthesevereparesistocompleteparalysisgroup,theriskofunsatisfactoryrecoverywithcorticosteroidaloneis27per100andthecorrespondingriskwithantiviralsandcorticosteroidsis20per100(95%CI;15–27)resultinginanabsoluteriskreductionof7%(95%CI,0–12%).

Thedosingregimenforantiviralswasheterogenousacrosstheincludedstudies.Fivestudiesusedvalacyclovir,37,38,50,51,52whilethreeusedacyclovir.36,53,54Nostudiesusedataperedregimen.Treatmentdurationvariedbetween5to10days—threestudiesuseda5dayregimen;50,51,533studiesuseda7dayregimen;37,38,52and2studiesuseda10dayregimen.36,54Allstudiesprescribingacyclovirusedaminimum