Clinical practice guidelines for the ... - Guideline Central

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit ... 1995 (revised 2013 Jan) ... Togglenavigation Shop Library GuidelineSummaries MEDLINE/PubMed ePSS DrugInformation ClinicalTrials Calculators QualityMeasures About AboutGuidelineCentral FrequentlyAskedQuestions Testimonials Blog Careers Contact MyLibrary Search 0itemsincart MyAccount Help LogOut LogIn Register 0 Login Register ViewCart/Checkout MyAccount LogOut LogIn ContactUs Go! TableofContents GuidelineDeveloper(s) DateReleased FullTextGuideline Recommendations EvidenceSupportingTheRecommendations ImplementationOfTheGuideline Benefits/harmsOfImplementingTheGuidelineRecommendations RatingSchemeForTheStrengthOfTheRecommendations QualifyingStatements Methodology IdentifyingInformationAndAvailability Scope RegulatoryAlert Contraindications InstituteOfMedicine(iom)NationalHealthcareQualityReportCategories Disclaimer Print FullScreen IncreaseFont DecreaseFont CreateNote ViewAllNotes PageNotes Therearenonotestodisplay.Addanote. SearchContent Search Clear MyLibrary AddtoLibrary ViewLibrary RecentlyAdded Pleaseregisterorlogintocreateanduseyourlibrary. GuidelineDeveloper(s)SocietyofCriticalCareMedicineDateReleased1995(revised2013Jan)FullTextGuidelineClinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit.RecommendationsMajorRecommendationsThegradesofevidence(A-C)andlevelsofrecommendations(1-2,infavororagainst)aredefinedattheendofthe"MajorRecommendations"field.PainandAnalgesiaIncidenceofpainAdultmedical,surgical,andtraumaintensivecareunit(ICU)patientsroutinelyexperiencepain,bothatrestandwithroutineICUcare.(B)Paininadultcardiacsurgerypatientsiscommonandpoorlytreated;womenexperiencemorepainthanmenaftercardiacsurgery.(B)ProceduralpainiscommoninadultICUpatients.(B)PainassessmentThetaskforcerecommendsthatpainberoutinelymonitoredinalladultICUpatients.(+1B)TheBehavioralPainScale(BPS)andtheCritical-CarePainObservationTool(CPOT)arethemostvalidandreliablebehavioralpainscalesformonitoringpaininmedical,postoperative,ortrauma(exceptforbraininjury)adultICUpatientswhoareunabletoself-reportandinwhommotorfunctionisintactandbehaviorsareobservable.UsingthesescalesinotherICUpatientpopulationsandtranslatingthemintoforeignlanguagesotherthanFrenchorEnglishrequirefurthervalidationtesting.(B)Thetaskforcedoesnotsuggestthatvitalsigns(orobservationalpainscalesthatincludevitalsigns)beusedaloneforpainassessmentinadultICUpatients.(–2C)Thetaskforcesuggeststhatvitalsignsmaybeusedasacuetobeginfurtherassessmentofpaininthesepatients,however.(+2C)TreatmentofpainThetaskforcerecommendsthatpreemptiveanalgesiaand/ornonpharmacologicinterventions(e.g.,relaxation)beadministeredtoalleviatepaininadultICUpatientspriortochesttuberemoval.(+1C)ThetaskforcesuggeststhatforothertypesofinvasiveandpotentiallypainfulproceduresinadultICUpatients,preemptiveanalgesictherapyand/ornonpharmacologicinterventionsmayalsobeadministeredtoalleviatepain.(+2C)Thetaskforcerecommendsthatintravenous(IV)opioidsbeconsideredasthefirst-linedrugclassofchoicetotreatnon-neuropathicpainincriticallyillpatients.(+1C)AllavailableIVopioids,whentitratedtosimilarpainintensityendpoints,areequallyeffective.(C)Thetaskforcesuggeststhatnonopioidanalgesicsbeconsideredtodecreasetheamountofopioidsadministered(ortoeliminatetheneedforIVopioidsaltogether)andtodecreaseopioid-relatedsideeffects.(+2C)Thetaskforcerecommendsthateitherenterallyadministeredgabapentinorcarbamazepine,inadditiontoIVopioids,beconsideredfortreatmentofneuropathicpain.(+1A)Thetaskforcerecommendsthatthoracicepiduralanesthesia/analgesiabeconsideredforpostoperativeanalgesiainpatientsundergoingabdominalaorticaneurysmsurgery.(+1B)Thetaskforceprovidesnorecommendationforusingalumbarepiduraloverparenteralopioidsforpostoperativeanalgesiainpatientsundergoingabdominalaorticaneurysmsurgery,duetoalackofbenefitofepiduraloverparenteralopioidsinthispatientpopulation.(0,A)Thetaskforceprovidesnorecommendationfortheuseofthoracicepiduralanalgesiainpatientsundergoingeitherintrathoracicornonvascularabdominalsurgicalprocedures,duetoinsufficientandconflictingevidenceforthismodeofanalgesicdeliveryinthesepatients.(0,B)Thetaskforcesuggeststhatthoracicepiduralanalgesiabeconsideredforpatientswithtraumaticribfractures.(+2B)Thetaskforceprovidesnorecommendationforneuraxial/regionalanalgesiaoversystemicanalgesiainmedicalICUpatients,duetolackofevidenceinthispatientpopulation.(0,NoEvidence)AgitationandSedationDepthofsedationvs.clinicaloutcomesMaintaininglightlevelsofsedationinadultICUpatientsisassociatedwithimprovedclinicaloutcomes(e.g.,shorterdurationofmechanicalventilationandashorterICUlengthofstay[LOS]).(B)Maintaininglightlevelsofsedationincreasesthephysiologicstressresponse,butisnotassociatedwithanincreasedincidenceofmyocardialischemia.(B)Theassociationbetweendepthofsedationandpsychologicalstressinthesepatientsremainsunclear.(C)ThetaskforcerecommendsthatsedativemedicationsbetitratedtomaintainalightratherthanadeeplevelofsedationinadultICUpatients,unlessclinicallycontraindicated.(+1B)MonitoringdepthofsedationandbrainfunctionTheRichmondAgitation-SedationScale(RASS)andSedation-AgitationScale(SAS)arethemostvalidandreliablesedationassessmenttoolsformeasuringqualityanddepthofsedationinadultICUpatients.(B)Thetaskforcedoesnotrecommendthatobjectivemeasuresofbrainfunction(e.g.,auditoryevokedpotentials[AEPs],BispectralIndex[BIS],NarcotrendIndex[NI],PatientStateIndex[PSI],orstateentropy[SE])beusedastheprimarymethodtomonitordepthofsedationinnoncomatose,nonparalyzedcriticallyilladultpatients,asthesemonitorsareinadequatesubstitutesforsubjectivesedationscoringsystems.(–1B)Thetaskforcesuggeststhatobjectivemeasuresofbrainfunction(e.g.,AEPs,BIS,NI,PSI,orSE)beusedasanadjuncttosubjectivesedationassessmentsinadultICUpatientswhoarereceivingneuromuscularblockingagents,assubjectivesedationassessmentsmaybeunobtainableinthesepatients.(+2B)Thetaskforcerecommendsthatelectroencephalogram(EEG)monitoringbeusedtomonitornonconvulsiveseizureactivityinadultICUpatientswitheitherknownorsuspectedseizures,ortotitrateelectrosuppressivemedicationtoachieveburstsuppressioninadultICUpatientswithelevatedintracranialpressure.(+1A)ChoiceofsedativeThetaskforcesuggeststhatsedationstrategiesusingnonbenzodiazepinesedatives(eitherpropofolordexmedetomidine)maybepreferredoversedationwithbenzodiazepines(eithermidazolamorlorazepam)toimproveclinicaloutcomesinmechanicallyventilatedadultICUpatients.(+2B)DeliriumOutcomesassociatedwithdeliriumDeliriumisassociatedwithincreasedmortalityinadultICUpatients.(A)DeliriumisassociatedwithprolongedICUandhospitalLOSinadultICUpatients.(A)Deliriumisassociatedwiththedevelopmentofpost-ICUcognitiveimpairmentinadultICUpatients.(B)DetectingandmonitoringdeliriumThetaskforcerecommendsroutinemonitoringofdeliriuminadultICUpatients.(+1B)TheConfusionAssessmentMethodfortheICU(CAM-ICU)andtheIntensiveCareDeliriumScreeningChecklist(ICDSC)arethemostvalidandreliabledeliriummonitoringtoolsinadultICUpatients.(A)RoutinemonitoringofdeliriuminadultICUpatientsisfeasibleinclinicalpractice.(B)DeliriumriskfactorsFourbaselineriskfactorsarepositivelyandsignificantlyassociatedwiththedevelopmentofdeliriumintheICU:preexistingdementia,historyofhypertensionand/oralcoholism,andahighseverityofillnessatadmission.(B)ComaisanindependentriskfactorforthedevelopmentofdeliriuminICUpatients.(B)ConflictingdatasurroundtherelationshipbetweenopioiduseandthedevelopmentofdeliriuminadultICUpatients.(B)BenzodiazepineusemaybeariskfactorforthedevelopmentofdeliriuminadultICUpatients.(B)ThereareinsufficientdatatodeterminetherelationshipbetweenpropofoluseandthedevelopmentofdeliriuminadultICUpatients.(C)InmechanicallyventilatedadultICUpatientsatriskofdevelopingdelirium,dexmedetomidineinfusionsadministeredforsedationmaybeassociatedwithalowerprevalenceofdeliriumcomparedtobenzodiazepineinfusions.(B)DeliriumpreventionThetaskforcerecommendsperformingearlymobilizationofadultICUpatientswheneverfeasibletoreducetheincidenceanddurationofdelirium.(+1B)ThetaskforceprovidesnorecommendationforusingapharmacologicdeliriumpreventionprotocolinadultICUpatients,asnocompellingdatademonstratethatthisreducestheincidenceordurationofdeliriuminthesepatients.(0,C)ThetaskforceprovidesnorecommendationforusingacombinednonpharmacologicandpharmacologicdeliriumpreventionprotocolinadultICUpatients,asthishasnotbeenshowntoreducetheincidenceofdeliriuminthesepatients.(0,C)ThetaskforcedoesnotsuggestthateitherhaloperidoloratypicalantipsychoticsbeadministeredtopreventdeliriuminadultICUpatients.(–2C)ThetaskforceprovidesnorecommendationfortheuseofdexmedetomidinetopreventdeliriuminadultICUpatients,asthereisnocompellingevidenceregardingitseffectivenessinthesepatients.(0,C)DeliriumtreatmentThereisnopublishedevidencethattreatmentwithhaloperidolreducesthedurationofdeliriuminadultICUpatients.(NoEvidence)AtypicalantipsychoticsmayreducethedurationofdeliriuminadultICUpatients.(C)ThetaskforcedoesnotrecommendadministeringrivastigminetoreducethedurationofdeliriuminICUpatients.(–1B)Thetaskforcedoesnotsuggestusingantipsychoticsinpatientsatsignificantriskfortorsadesdepointes(i.e.,patientswithbaselineprolongationofQ-Tinterval[corrected][QTc],patientsreceivingconcomitantmedicationsknowntoprolongtheQTcinterval,orpatientswithahistoryofthisarrhythmia).(–2C)ThetaskforcesuggeststhatinadultICUpatientswithdeliriumunrelatedtoalcoholorbenzodiazepinewithdrawal,continuousIVinfusionsofdexmedetomidineratherthanbenzodiazepineinfusionsbeadministeredforsedationtoreducethedurationofdeliriuminthesepatients.(+2B)StrategiesforManagingPain,Agitation,andDeliriumtoImproveICUOutcomesThetaskforcerecommendseitherdailysedationinterruptionoralighttargetlevelofsedationberoutinelyusedinmechanicallyventilatedadultICUpatients(+1B)Thetaskforcesuggeststhatanalgesia-firstsedationbeusedinmechanicallyventilatedadultICUpatients.(+2B)ThetaskforcerecommendspromotingsleepinadultICUpatientsbyoptimizingpatients'environments,usingstrategiestocontrollightandnoise,clusteringpatientcareactivities,anddecreasingstimuliatnighttoprotectpatients'sleepcycles.(+1C)ThetaskforceprovidesnorecommendationforusingspecificmodesofmechanicalventilationtopromotesleepinmechanicallyventilatedadultICUpatients,asinsufficientevidenceexistsfortheefficacyoftheseinterventions.(0,NoEvidence)ThetaskforcerecommendsusinganinterdisciplinaryICUteamapproachthatincludesprovidereducation,preprintedand/orcomputerizedprotocolsandorderforms,andqualityICUroundscheckliststofacilitatetheuseofpain,agitation,anddeliriummanagementguidelinesorprotocolsinadultICUs.(+1B)Definitions:FactorsThatAffecttheQualityofEvidenceaLevelofEvidenceQualityofEvidenceTypeofEvidenceDefinitionAHighHighqualityrandomizedcontrolledtrial(RCT)Furtherresearchisunlikelytochangetheguidelinecommittee'sconfidenceintheestimateofeffect.BModerateRCTwithsignificantlimitations(downgraded)b,orhigh-qualityobservationalstudy(OS)(upgraded)cFurtherresearchislikelytohaveanimportantimpactontheguidelinecommittee'sconfidenceintheestimateofeffectandmaychangetheestimate.CLowOSFurtherresearchisverylikelytohaveanimportantimpactontheguidelinecommittee'sconfidenceintheestimateofeffectandislikelytochangetheestimate.aAdaptedfromGuyattetal;GradingofRecommendations,Assessment,DevelopmentandEvaluation(GRADE)WorkingGroup:GRADE:Anemergingconsensusonratingqualityofevidenceandstrengthofrecommendations.BMJ2008;336:924–926.bRCTswithsignificantlimitations:1)studydesignlimitations(planning,implementationbias);2)inconsistencyofresults;3)indirectnessofevidence;4)imprecisionofresults;5)highlikelihoodofreportingbias.cHigh-qualityOS:1)largemagnitudeoftreatmenteffect;2)evidenceofadose-responserelationship;3)plausiblebiaseswoulddecreasethemagnitudeofanapparenttreatmenteffect.LevelsofRecommendationsAstrongrecommendationeitherinfavorof(+1)oragainst(–1)aninterventionimpliedthatthemajorityoftaskforcemembersbelievedthatthebenefitsoftheinterventionsignificantlyoutweighedtherisks(orviceversa)andthatthemajorityofpatientsandproviderswouldpursuethiscourseofaction(ornot),giventhechoice.Aweakrecommendationeitherinfavorof(+2)oragainst(–2)aninterventionimpliedthatthebenefitsoftheinterventionlikelyoutweighedtherisks(orviceversa),butthattaskforcememberswerenotconfidentaboutthesetrade-offs,eitherbecauseofalowqualityofevidenceorbecausethetrade-offsbetweenrisksandbenefitswerecloselybalanced.Onthebasisofthisinformation,mostpeoplemightpursuethiscourseofaction(ornot),butasignificantnumberofpatientsandproviderswouldchooseanalternativecourseofaction.Anorecommendation(0)couldalsobemadeduetoeitheralackofevidenceoralackofconsensusamongsubcommitteemembers.ClinicalAlgorithm(s)NoneprovidedEvidenceSupportingtheRecommendationsTypeofEvidenceSupportingtheRecommendationsThetypeofsupportingevidenceisidentifiedandgradedforeachrecommendation(seethe"MajorRecommendations"field).ImplementationoftheGuidelineDescriptionofImplementationStrategyToolsforFacilitatingtheApplicationoftheGuidelinestoBedsideCareClosingthegapbetweentheevidencehighlightedintheseguidelinesandintensivecareunit(ICU)practicewillbeasignificantchallengeforICUcliniciansandisbestaccomplishedusingamultifaceted,interdisciplinaryapproach.Therecommendationssupportedbyclinicalpracticeguidelinesshouldbeadaptedtolocalpracticepatternsandresourceavailability,andusedasatemplateforinstitution-specificprotocolsandordersets.Successfulimplementationwillrequireaugmentationwitheducation,engagementoflocalthoughtleaders,point-of-usereminders,andcaregiver-specificpracticefeedback,togetherwithcontinuousprotocolevaluationandmodification.Incorporatingelectronicallybasedguidelinesintoclinicaldecision-supporttoolsmayfacilitatebedsideknowledgetransferandapplication.Tosupportthiseffort,theguidelinedevelopershavedevelopedapocketcardsummarizingtheseguidelinerecommendations(Figure2intheoriginalguidelinedocument),andatemplateforapain,agitation,anddelirium(PAD)carebundle(Figure3intheoriginalguidelinedocument).ImplementationToolsPocketGuide/ReferenceCardsQuickReferenceGuides/PhysicianGuidesResourcesBenefits/HarmsofImplementingtheGuidelineRecommendationsPotentialBenefitsAppropriatemanagementofcriticallyilladultswithpain,agitation,anddeliriumintheintensivecareunit(ICU)PotentialHarmsOpiateAnalgesicTherapyOpiateSideEffectsandOtherInformationFentanylLesshypotensionthanwithmorphine.Accumulationwithhepaticimpairment.HydromorphoneTherapeuticoptioninpatientstoleranttomorphine/fentanyl.Accumulationwithhepatic/renalimpairment.MorphineAccumulationwithhepatic/renalimpairment.Histaminerelease.MethadoneMaybeusedtoslowthedevelopmentoftolerancewherethereisanescalationofopioiddosingrequirements.Unpredictablepharmacokinetics;unpredictablepharmacodynamicsinopiatenaïvepatients.MonitorQ-Tinterval(corrected)(QTc).RemifentanilNoaccumulationinhepatic/renalfailure.UseIBWifbodyweight>130%IBW.NonopiateAnalgesicTherapyNonopiateSideEffectsandOtherInformationKetamineAttenuatesthedevelopmentofacutetolerancetoopioids.Maycausehallucinationsandotherpsychologicaldisturbances.KeterolacAvoidnonsteroidalanti-inflammatorydrugsinfollowingconditions:renaldysfunction;gastrointestinalbleeding;plateletabnormality;concomitantangiotensinconvertingenzymeinhibitortherapy,congestiveheartfailure,cirrhosis,asthma.IbuprofenAvoidnonsteroidalanti-inflammatorydrugsinfollowingconditions:renaldysfunction;gastrointestinalbleeding;plateletabnormality;concomitantangiotensinconvertingenzymeinhibitortherapy,congestiveheartfailure,cirrhosis,asthma.Contraindicatedforthetreatmentofperioperativepainincoronaryarterybypassgraftsurgery.GabapentinSideeffects:(common)sedation,confusion,dizziness,ataxia.Adjustdosinginrenalfailurepts.Abruptdiscontinuationassociatedwithdrugwithdrawalsyndrome,seizures.CarbamazepineSideeffects:(common)nystagmus,dizziness,diplopia,lightheadedness,lethargy;(rare)aplasticanemia,andagranulocytosis;Stevens–JohnsonsyndromeortoxicepidermalnecrolysiswithHLA-B1502gene.Multipledruginteractionsduetohepaticenzymeinduction.SedativeMedicationsAgentAdverseEffectsMidazolamRespiratorydepression,hypotension LorazepamRespiratorydepression,hypotension;propylene glycol-relatedacidosis,nephrotoxicityDiazepamRespiratorydepression,hypotension,phlebitisPropofolPainoninjection,hypotension,respiratorydepression,hypertriglyceridemia,pancreatitis,allergicreactions,propofolrelatedinfusionsyndrome;deepsedationwithpropofolisassociatedwithsignificantlylongeremergencetimesthanwithlightsedationDexmedetomidineBradycardia,hypotension;hypertensionwithloadingdose;lossofairwayreflexesRatingSchemefortheStrengthoftheRecommendationsAstrongrecommendationeitherinfavorof(+1)oragainst(–1)aninterventionimpliedthatthemajorityoftaskforcemembersbelievedthatthebenefitsoftheinterventionsignificantlyoutweighedtherisks(orviceversa)andthatthemajorityofpatientsandproviderswouldpursuethiscourseofaction(ornot),giventhechoice.Aweakrecommendationeitherinfavorof(+2)oragainst(–2)aninterventionimpliedthatthebenefitsoftheinterventionlikelyoutweighedtherisks(orviceversa),butthattaskforcememberswerenotconfidentaboutthesetrade-offs,eitherbecauseofalowqualityofevidenceorbecausethetrade-offsbetweenrisksandbenefitswerecloselybalanced.Onthebasisofthisinformation,mostpeoplemightpursuethiscourseofaction(ornot),butasignificantnumberofpatientsandproviderswouldchooseanalternativecourseofaction.Anorecommendation(0)couldalsobemadeduetoeitheralackofevidenceoralackofconsensusamongsubcommitteemembers.QualifyingStatementsQualifyingStatementsTheguidelinedocumentismeanttohelpclinicianstakeamoreintegratedapproachtomanagepain,agitation,anddelirium(PAD)incriticallyillpatients.Cliniciansshouldadapttheguidelinedocumenttothecontextofindividualpatientcareneedsandtheavailableresourcesoftheirlocalhealthcaresystem.Inaddition,frequentmonitoringofpain,depthofsedation,anddeliriumshouldoccurusingvalidandreliableassessmenttools;patientsshouldreceivepreemptivetreatmentforpain;sedationshouldonlybereceivedifrequired;andpatientsshouldbeabletopurposefullyrespondtocommandsthroughtitrationofsedatives.Theguidelinedocumentisnotmeanttobeproscriptiveorappliedinabsoluteterms.MethodologyMethodsUsedtoCollect/SelecttheEvidenceSearchesofElectronicDatabasesDescriptionofMethodsUsedtoCollect/SelecttheEvidenceTofacilitatetheliteraturereview,subcommitteesdevelopedacomprehensivelistofrelatedkeywords.Aprofessionallibrarianexpandedandorganizedthiskeywordlist;developedcorrespondingmedicalsubjectheading(MeSH)terms(seetheSupplementalDigitalContentfortheoriginalguidelinedocument[seethe"AvailabilityofCompanionDocuments"field]);searchedrelevantclinicaldatabases;andcreatedanelectronic,Web-based,password-protecteddatabaseusingRefworkssoftware(Bethesda,MD).Eightdatabaseswereincludedinallsearches:PubMed,MEDLINE,CochraneDatabaseofSystematicReviews,CochraneCentralRegisterofControlledTrials,CINAHL,Scopus,ISIWebofScience,andtheInternationalPharmaceuticalAbstracts.Searchparametersincludedpublished(orinpress)English-onlymanuscriptsonadulthumans(>18yr),fromDecember1999(thesearchlimitforthe2002guidelines)throughDecember2010.Studieswithlessthan30patients,editorials,narrativereviews,casereports,animalorinvitrostudies,andletterstotheeditorwereexcluded.Biweeklyautomatedsearcheswerecontinuedbeyondthisdate,andrelevantarticleswereincorporatedintotheguidelinesthroughJuly2012,butstudiespublishedafterDecember2010werenotincludedintheevidencereviewandvotingprocess.The2002guidelinereferenceswerealsoincludedinthedatabase,andtargetedsearchesoftheliteraturepublishedbeforeDecember1999wereperformedasneeded.Over19,000referenceswereultimatelyincludedintheRefworksdatabase.NumberofSourceDocumentsNotstatedMethodsUsedtoAssesstheQualityandStrengthoftheEvidenceExpertConsensus(DelphiMethod)WeightingAccordingtoaRatingScheme(SchemeGiven)RatingSchemefortheStrengthoftheEvidenceFactorsThatAffecttheQualityofEvidenceaLevelofEvidenceQualityofEvidenceTypeofEvidenceDefinitionAHighHighqualityrandomizedcontrolledtrial(RCT)Furtherresearchisunlikelytochangetheguidelinecommittee'sconfidenceintheestimateofeffect.BModerateRCTwithsignificantlimitations(downgraded)b,orhigh-qualityobservationalstudy(OS)(upgraded)cFurtherresearchislikelytohaveanimportantimpactontheguidelinecommittee'sconfidenceintheestimateofeffectandmaychangetheestimate.CLowOSFurtherresearchisverylikelytohaveanimportantimpactontheguidelinecommittee'sconfidenceintheestimateofeffectandislikelytochangetheestimate.aAdaptedfromGuyattetal;GradingofRecommendations,Assessment,DevelopmentandEvaluation(GRADE)WorkingGroup:GRADE:Anemergingconsensusonratingqualityofevidenceandstrengthofrecommendations.BMJ2008;336:924–926.bRCTswithsignificantlimitations:1)studydesignlimitations(planning,implementationbias);2)inconsistencyofresults;3)indirectnessofevidence;4)imprecisionofresults;5)highlikelihoodofreportingbias.cHigh-qualityOS:1)largemagnitudeoftreatmenteffect;2)evidenceofadose-responserelationship;3)plausiblebiaseswoulddecreasethemagnitudeofanapparenttreatmenteffect.MethodsUsedtoAnalyzetheEvidenceMeta-AnalysisReviewofPublishedMeta-AnalysesSystematicReviewwithEvidenceTablesDescriptionoftheMethodsUsedtoAnalyzetheEvidenceThestatementsandrecommendationsinthe2012versionoftheguidelinesweredevelopedusingtheGradingofRecommendations,Assessment,DevelopmentandEvaluation(GRADE)methodology,astructuredsystemforratingqualityofevidenceandgradingstrengthofrecommendationinclinicalpractice(http://www.gradeworkinggroup.org).SubcommitteesworkedwithmembersoftheGRADEWorkingGrouptophraseallclinicalquestionsineither"descriptive"or"actionable"terms.TheystructuredactionablequestionsinthePopulation,Intervention,Comparison,Outcomesformatandclassifiedclinicaloutcomesrelatedtoeachinterventionascritical,important,orunimportanttoclinicaldecisionmaking.Onlyimportantandcriticaloutcomeswereincludedintheevidencereview,andonlycriticaloutcomeswereincludedindevelopingrecommendations.SubcommitteememberssearchedthedatabaseforrelevantarticlesanduploadedcorrespondingPortableDocumentFormat(PDFs)tofacilitategroupreview.TwosubcommitteemembersindependentlycompletedaGRADEevidenceprofilesummarizingthefindingsofeachstudyandevaluatedthequalityofevidence.Thequalityofevidencewasjudgedtobehigh(levelA),moderate(levelB),orlow/verylow(levelC),basedonbothstudydesignandspecificstudycharacteristics,whichcouldresultinareviewereitherdowngradingorupgradingthequalityoftheevidence(seeTable1oftheoriginalguidelinedocument[seethe"GuidelineAvailability"field]).Ifmultiplestudiesrelatedtoaparticularoutcomedemonstrateddisparateresults,andnopublishedsystematicreviewsonthetopicexisted,ameta-analysisoftherelevantliteraturewasperformedbyamemberoftheGRADEWorkingGroup.MethodsUsedtoFormulatetheRecommendationsExpertConsensus(Delphi)ExpertConsensus(NominalGroupTechnique)DescriptionofMethodsUsedtoFormulatetheRecommendationsSubcommitteescollectivelyreviewedtheevidenceprofilesforeachquestion,andusinganominalgrouptechnique,determinedtheoverallqualityofevidence(forbothdescriptiveandactionablequestions),thestrengthofrecommendation(foractionablequestionsonly),anddraftedevidencesummariesforreviewbyothertaskforcemembers.Thestrengthofrecommendationswasdefinedaseitherstrong(1)orweak(2),andeitherfor(+)oragainst(–)anintervention,basedonboththequalityofevidenceandtherisksandbenefitsacrossallcriticaloutcomes(Table2oftheoriginalguidelinedocument).Anorecommendation(0)couldalsobemadeduetoeitheralackofevidenceoralackofconsensusamongsubcommitteemembers.Consensusstatementsbasedonexpertopinionalonewerenotusedwhenevidencecouldnotsupportarecommendation.Astrongrecommendationeitherinfavorof(+1)oragainst(–1)aninterventionimpliedthatthemajorityoftaskforcemembersbelievedthatthebenefitsoftheinterventionsignificantlyoutweighedtherisks(orviceversa)andthatthemajorityofpatientsandproviderswouldpursuethiscourseofaction(ornot),giventhechoice.Aweakrecommendationeitherinfavorof(+2)oragainst(–2)aninterventionimpliedthatthebenefitsoftheinterventionlikelyoutweighedtherisks(orviceversa),butthattaskforcememberswerenotconfidentaboutthesetradeoffs,eitherbecauseofalowqualityofevidenceorbecausethetrade-offsbetweenrisksandbenefitswerecloselybalanced.Onthebasisofthisinformation,mostpeoplemightpursuethiscourseofaction(ornot),butasignificantnumberofpatientsandproviderswouldchooseanalternativecourseofaction.Throughouttheseguidelines,forallstrongrecommendations,thephrase"Thetaskforcerecommends…"wasused,andforallweakrecommendations,"Thetaskforcesuggests…"wasused.GroupconsensusforallstatementsandrecommendationswasachievedusingamodifiedDelphimethodwithananonymousvotingscheme.Taskforcemembersreviewedthesubcommittees'GradingofRecommendations,Assessment,DevelopmentandEvaluation(GRADE)EvidenceSummaries,andstatementsandrecommendations,andvotedandcommentedanonymouslyoneachstatementandrecommendationusinganon-lineelectronicsurveytool.Consensusonthestrengthofevidenceforeachquestionrequiredamajority(>50%)vote.Consensusonthestrengthofrecommendationswasdefinedasfollows:arecommendationinfavorofanintervention(orthecomparator)requiredatleast50%ofalltaskforcemembersvotinginfavor,withlessthan20%votingagainst;failuretomeetthesevotingthresholdsresultedinnorecommendationbeingmade.Forarecommendationtobegradedasstrongratherthanweak,atleast70%ofthosevotinghadtovoteforastrongrecommendation,otherwiseitreceivedaweakrecommendation.Pollingresultsandcommentswerethensummarizedanddistributedtoallpain,agitation,anddelirium(PAD)guidelinetaskforcemembersforreview.Whenoneroundofvotingfailedtoproducegroupconsensus,additionaldiscussionandasecondand/orthirdroundofvotingoccurred.CostAnalysisTheguidelinedevelopersreviewedpublishedcostanalyses.MethodofGuidelineValidationExternalPeerReviewInternalPeerReviewDescriptionofMethodofGuidelineValidationTheseguidelineshavebeenreviewedandendorsedbytheAmericanCollegeofChestPhysiciansandtheAmericanAssociationforRespiratoryCare;aresupportedbytheAmericanAssociationforRespiratoryCare;andhavebeenreviewedbytheNewZealandIntensiveCareSociety.IdentifyingInformationandAvailabilityBibliographicSource(s)BarrJ,FraserGL,PuntilloK,ElyEW,GélinasC,DastaJF,DavidsonJE,DevlinJW,KressJP,JoffeAM,CoursinDB,HerrDL,TungA,RobinsonBRH,FontaineDK,RamsayMA,RikerRR,SesslerCN,PunB,SkrobikY,JaeschkeR,AmericanCollegeofCriticalCareMedicine.Clinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit.CritCareMed.2013Jan;41(1):263-306.[472references]PubMedAdaptationNotapplicable:Theguidelinewasnotadaptedfromanothersource.Source(s)ofFundingSupportingOrganizations:AmericanCollegeofCriticalCareMedicine(ACCM)inconjunctionwithSocietyofCriticalCareMedicine(SCCM)andAmericanSocietyofHealth-SystemPharmacists(ASHP)GuidelineCommitteeTaskForceforClinicalPracticeGuidelinesforSystemicAnalgesiaandSedationforPatientsintheIntensiveCareUnitCompositionofGroupThatAuthoredtheGuidelineTaskForceMembers:JulianaBarr,MD,FCCM;GillesL.Fraser,PharmD,FCCM;KathleenPuntillo,RN,PhD,FAAN,FCCM;E.WesleyEly,MD,MPH,FACP,FCCM;CélineGélinas,RN,PhD;JosephF.Dasta,MSc,FCCM,FCCP;JudyE.Davidson,DNP,RN;JohnW.Devlin,PharmD,FCCM,FCCP;JohnP.Kress,MD;AaronM.Joffe,DO;DouglasB.Coursin,MD;DanielL.Herr,MD,MS,FCCM;AveryTung,MD;BryceR.H.Robinson,MD,FACS;DorrieK.Fontaine,PhD,RN,FAAN;MichaelA.Ramsay,MD;RichardR.Riker,MD,FCCM;CurtisN.Sessler,MD,FCCP,FCCM;BrendaPun,MSN,RN,ACNP;YoannaSkrobik,MD,FRCP;RomanJaeschke,MDFinancialDisclosures/ConflictsofInterestTominimizetheperceptionofbiasintheseGuidelines,individualTaskForcememberswithasignificantconflictofinterestonaparticulartopicwererecusedfromgradingtheliterature,writingevidencesummaries,anddevelopingspecificstatementsandrecommendationsonthattopic.Mr.DastahasconsultancieswithHospira,AxelRx,CadencePharmaceuticals,andPaciraPharmaceuticalsandhasreceivedhonoraria/speakingfeesfromtheFranceFoundation(speakersbureaucontinuingmedicaleducation[CME]program)sponsoredbyHospira.Dr.Devlinhasreceivedhonoraria/speakingfees,consultancies,andgrantsfromHospira.Dr.Elyhasreceivedhonoraria/speakingfeesfromGSKandHospira;andhasreceivedgrantsfromHospira,Pfizer,andAspect.Dr.Herrhasreceivedhonoraria/speakingfeesfromHospira.Dr.Kresshasreceivedhonoraria/speakingfeesfromHospira;andhasreceivedagrantfromHospira(unrestrictedresearch).Ms.Punhasreceivedhonoraria/speakingfeesfromHospira.Dr.Ramsayhasreceivedhonoraria/speakingfeesfromHospiraandMasimo;andhasreceivedagrantfromMasimo.Dr.RikerhasconsultancieswithMasimo;andhasreceivedhonoraria/speakingfeesfromOrion.Dr.Sesslerhasreceivedhonoraria/speakingfeesfromHospiraandconsultingfeesfromMassimo.Theremainingauthorshavenotdisclosedanypotentialconflictsofinterest.GuidelineEndorser(s)AmericanAssociationforRespiratoryCare-ProfessionalAssociationAmericanCollegeofChestPhysicians-MedicalSpecialtySocietyGuidelineStatusThisisthecurrentreleaseoftheguideline.Thisguidelineupdatesapreviousversion:Clinicalpracticeguidelinesforthesustaineduseofsedativesandanalgesicsinthecriticallyilladult.AmJHealthSystPharm2002Jan15;59(2):150-78.[235references]GuidelineAvailabilityElectroniccopies:AvailableinPortableDocumentFormat(PDF)fromthe SocietyofCriticalCareMedicine(SCCM)Website.Printcopies:AvailablefromtheSocietyofCriticalCareMedicine,500MidwayDrive,MountProspect,IL60056;Phone:(847)827-6869;Fax:(847)827-6886;on-linethroughtheSCCMBookstore.AvailabilityofCompanionDocumentsThefollowingisavailable:Clinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit.GuidelineMESHTerms.Electroniccopies:AvailablefromtheSocietyforCriticalCareMedicine(SCCM)Website.Apocketcardoperationalizingthepain,agitation,anddelirium(PAD)guidelinerecommendations(frontside)andsummarizingspecificPADguidelinestatementsandrecommendations(backside),andatemplateforaPADcarebundlecanbefoundintheoriginalguidelinedocument.PatientResourcesNoneavailableNGCStatusThisNGCsummarywascompletedbyECRIonJuly22,2002.TheinformationwasverifiedbytheguidelinedevelopersonAugust1,2002.ThissummarywasupdatedbyECRIonJanuary12,2005followingthereleaseofapublichealthadvisoryfromtheU.S.FoodandDrugAdministrationregardingtheuseofsomenonsteroidalanti-inflammatorydrugproducts.ThissummarywasupdatedonApril15,2005followingthewithdrawalofBextra(valdecoxib)fromthemarketandthereleaseofheightenedwarningsforCelebrex(celecoxib)andothernonselectivenonsteroidalanti-inflammatorydrugs(NSAIDs).ThissummarywasupdatedbyECRIonJune16,2005,followingtheU.S.FoodandDrugAdministrationadvisoryonCOX-2selectiveandnonselectivenonsteroidalanti-inflammatorydrugs(NSAIDs).ThissummarywasupdatedbyECRIInstituteonApril30,2007,followingtheFDAadvisoryonSedative-hypnoticdrugproducts.ThissummarywasupdatedbyECRIInstituteonOctober2,2007,followingtheU.S.FoodandDrugAdministration(FDA)advisoryonHaloperidol.ThissummarywasupdatedbyECRIInstituteonApril18,2013.TheupdatedinformationwasverifiedbytheguidelinedeveloperonMay14,2013.ThissummarywasupdatedbyECRIInstituteonOctober28,2013followingtheU.S.FoodandDrugAdministrationadvisoryonAcetaminophen.ThissummarywasupdatedbyECRIInstituteonSeptember18,2015followingtheU.S.FoodandDrugAdministrationadvisoryonnon-aspirinnonsteroidalanti-inflammatorydrugs(NSAIDs).ThissummarywasupdatedbyECRIInstituteonMay24,2016followingtheU.S.FoodandDrugAdministrationadvisoryonOlanzapine.ThissummarywasupdatedbyECRIInstituteonJune2,2016followingtheU.S.FoodandDrugAdministrationadvisoryonOpioidpainmedicines.CopyrightStatementThisNGCsummaryisbasedontheoriginalguideline,whichissubjecttotheguidelinedeveloper'scopyrightrestrictions.ScopeDisease/Condition(s)Criticalillnessrelated:PainanddiscomfortAgitationDeliriumSleepdeprivationGuidelineCategoryEvaluationManagementPreventionTreatmentClinicalSpecialtyAnesthesiologyCriticalCareEmergencyMedicineNeurologyNursingPulmonaryMedicineIntendedUsersAdvancedPracticeNursesHospitalsNursesPharmacistsPhysicianAssistantsPhysiciansRespiratoryCarePractitionersGuidelineObjective(s)Torecommendbestpracticesforassessing,treating,andpreventingpain,agitation,anddelirium(PAD)toimproveclinicaloutcomesinadultintensivecareunit(ICU)patientsTorevisethe"ClinicalPracticeGuidelinesfortheSustainedUseofSedativesandAnalgesicsintheCriticallyIllAdult"publishedinCriticalCareMedicinein2002TargetPopulationCriticallyilladult(>18years)intensivecareunit(ICU)patientsInterventionsandPracticesConsideredAssessmentPainassessment(self-reportusingNumericRatingScale[NRS],ifable;BehavioralPainScaleorCritical-CarePainObservationTool[CPOT],ifunabletoself-report)Assessmentofdepthandqualityofsedation(RichmondAgitationandSedationScale[RASS]orSedation-AgitationScale[SAS],orbrainfunctioningmonitoring,ifunderneuromuscularblockade)AssessmentofdeliriumriskfactorsDetectingandmonitoringdelirium(ConfusionAssessmentMethodfortheIntensiveCareUnit[CAM-ICU]andtheIntensiveCareDeliriumScreeningChecklist[ICDSC])Management/TreatmentTreatmentofpainPreemptiveanalgesiaand/ornonpharmacologicinterventions(e.g.,relaxation)NonopioidanalgesicstodecreaseopioiduseandsideeffectsIntravenous(IV)opioidsEnterallyadministeredgabapentinorcarbamazepineplusIVopioidsThoracicepiduralanesthesia/analgesiaTreatmentofagitationandsedationTitrationofsedativemedicationstotargetlightestlevelofsedationordailysedationinterruption(DSI)Monitoringdepthofsedationandbrainfunction(RASSandSAS)Objectivemeasuresofbrainfunction(e.g.,auditoryevokedpotentials,BispectralIndex,NarcotrendIndex,PatientStateIndex,orstateentropyasindicated)Electroencephalogrammonitoring(EEG)Sedationstrategiesusingnonbenzodiazepinesedatives(propofolordexmedetomidine)TreatmentofdeliriumEarlymobilizationofadultintensivecareunit(ICU)patientsConsiderationofdeliriumriskfactorsRoutinemonitoringofdeliriumIVdexmedetomidine,ifsedationisrequiredStrategiesformanagingpain,agitation,anddeliriumRoutinedailysedationinterruptionoralighttargetlevelofsedationinmechanicallyventilatedadultICUpatientsAnalgesia-firstsedationPromotingsleepinadultICUpatients(optimizingpatients'environments,strategiestocontrollightandnoise,clusteringpatientcareactivities,anddecreasingstimuliatnight)InterdisciplinaryICUteamapproach(providereducation,preprintedand/orcomputerizedprotocolsandorderforms,andqualityICUroundschecklists)PreventionPainpreventionPre-procedureanalgesiaand/ornon-pharmacologicinterventionsTreatmentofpainpriortosedationAgitationpreventionConsiderdailyspontaneousbreathingtrials(SBT)ConsiderearlymobilityandexercisewhenatgoalsedationlevelEEGmonitoringforpatientsatriskforseizuresorforburstsuppressiontherapyforincreasedintracranialpressureDeliriumpreventionIdentifydeliriumriskfactorsMobilizeandexerciseearlyPromotesleepRestartbaselinepsychiatricmedications,ifneededMajorOutcomesConsideredIncidenceandseverityof:AgitationDeliriumLong-termcognitiveimpairmentPainSedationDurationof:Intensivecareunit(ICU)lengthofstay(LOS)HospitalLOSMechanicalventilationuseMortalityRegulatoryAlertFDAWarning/RegulatoryAlertNotefromtheNationalGuidelineClearinghouse:Thisguidelinereferencesadrug(s)forwhichimportantrevisedregulatoryand/orwarninginformationhasbeenreleased.May10,2016–Olanzapine:TheU.S.FoodandDrugAdministration(FDA)iswarningthattheantipsychoticmedicineolanzapinecancauseararebutseriousskinreactionthatcanprogresstoaffectotherpartsofthebody.FDAisaddinganewwarningtothedruglabelsforallolanzapine-containingproductsthatdescribesthissevereconditionknownasDrugReactionwithEosinophiliaandSystemicSymptoms(DRESS).March22,2016–Opioidpainmedicines:TheU.S.FoodandDrugAdministration(FDA)iswarningaboutseveralsafetyissueswiththeentireclassofopioidpainmedicines.Thesesafetyrisksarepotentiallyharmfulinteractionswithnumerousothermedications,problemswiththeadrenalglands,anddecreasedsexhormonelevels.Theyarerequiringchangestothelabelsofallopioiddrugstowarnabouttheserisks.ContraindicationsContraindicationsAcetaminophenmaybecontraindicatedinpatientswithsignificanthepaticdysfunction.Nonsteroidalanti-inflammatorydrugsarecontraindicatedforthetreatmentofperioperativepainincoronaryarterybypassgraftsurgery.InstituteofMedicine(IOM)NationalHealthcareQualityReportCategoriesIOMCareNeedGettingBetterIOMDomainEffectivenessSafetyDisclaimerNGCDisclaimerTheNationalGuidelineClearinghouse™(NGC)doesnotdevelop,produce,approve,orendorsetheguidelinesrepresentedonthissite.AllguidelinessummarizedbyNGCandhostedonoursiteareproducedundertheauspicesofmedicalspecialtysocieties,relevantprofessionalassociations,publicorprivateorganizations,othergovernmentagencies,healthcareorganizationsorplans,andsimilarentities.GuidelinesrepresentedontheNGCWebsitearesubmittedbyguidelinedevelopers,andarescreenedsolelytodeterminethattheymeettheNGCInclusionCriteriawhichmaybefoundathttp://www.guideline.gov/about/inclusion-criteria.aspx.NGC,AHRQ,anditscontractorECRIInstitutemakenowarrantiesconcerningthecontentorclinicalefficacyoreffectivenessoftheclinicalpracticeguidelinesandrelatedmaterialsrepresentedonthissite.Moreover,theviewsandopinionsofdevelopersorauthorsofguidelinesrepresentedonthissitedonotnecessarilystateorreflectthoseofNGC,AHRQ,oritscontractorECRIInstitute,andinclusionorhostingofguidelinesinNGCmaynotbeusedforadvertisingorcommercialendorsementpurposes.Readerswithquestionsregardingguidelinecontentaredirectedtocontacttheguidelinedeveloper. RESOURCES FULLTEXTGUIDELINE Close CreateNote Page Clinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit Content Close SaveNote Close ViewNote Page Clinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit ViewAll Delete Close SaveNote Close AllNotes Page Clinicalpracticeguidelinesforthemanagementofpain,agitation,anddeliriuminadultpatientsintheintensivecareunit Close Togetstarted,loginorcreateyourfreeaccountCreateAccount × Close × Close OurCommitmenttoOurCustomer’sPrivacy ThankyouforbeingauserofGuidelineCentral! Aspartofourcontinuedeffortstowardsprotectingyourprivacyandpersonalinformation,we’vemaderecentupdatestoourprivacypolicy. Byupdatingourprivacypolicywithclearerlanguage,ourgoalistohelpyoubetterunderstandwhatdatawecollectandhowweusethatinformation. Whenwecollectyourdatathroughsitevisitsandaccountcreation,weagreetoneversellthatinformationtothird-parties. ThispersonalinformationisusedsolelytoprovideyouamorepersonalizedexperiencewhenusingtheGuidelineCentralwebsiteandapp. Atanytime,youmayoptoutoftrackingorrequestaccountdeletion. Pleasevisitourprivacypolicypageformoreinformation. Gotit! × Close YourAccount Login Email Password Login ForgotPassword? Register Email* Avalide-mailaddress.Alle-mailsfromthesystemwillbesenttothisaddress.Thee-mailaddressisnotmadepublicand willonlybeusedifyouwishtoreceiveanewpasswordorwishtoreceivecertainnewsornotificationsbye-mail. Password* Requiresatleastonecapitalletterandanumber. PasswordConfirmation* FirstName* LastName* Country UnitedStates ÅlandIslands Afghanistan Albania Algeria AmericanSamoa Andorra Angola Anguilla Antarctica AntiguaandBarbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belau Belgium Belize Benin Bermuda Bhutan Bolivia Bonaire,SaintEustatiusandSaba BosniaandHerzegovina Botswana BouvetIsland Brazil BritishIndianOceanTerritory BritishVirginIslands Brunei Bulgaria BurkinaFaso Burundi Cambodia Cameroon Canada CapeVerde CaymanIslands CentralAfricanRepublic Chad Chile China ChristmasIsland Cocos(Keeling)Islands Colombia Comoros Congo(Brazzaville) Congo(Kinshasa) CookIslands CostaRica Croatia Cuba Curaçao Cyprus CzechRepublic Denmark Djibouti Dominica DominicanRepublic Ecuador Egypt ElSalvador EquatorialGuinea Eritrea Estonia Ethiopia FalklandIslands FaroeIslands Fiji Finland France FrenchGuiana FrenchPolynesia FrenchSouthernTerritories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti HeardIslandandMcDonaldIslands Honduras HongKong Hungary Iceland India Indonesia Iran Iraq Ireland IsleofMan Israel Italy IvoryCoast Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg MacaoS.A.R.,China Macedonia Madagascar Malawi Malaysia Maldives Mali Malta MarshallIslands Martinique Mauritania Mauritius Mayotte Mexico Micronesia Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands NewCaledonia NewZealand Nicaragua Niger Nigeria Niue NorfolkIsland NorthKorea NorthernMarianaIslands Norway Oman Pakistan PalestinianTerritory Panama PapuaNewGuinea Paraguay Peru Philippines Pitcairn Poland Portugal PuertoRico Qatar Reunion Romania Russia Rwanda SãoToméandPríncipe SaintBarthélemy SaintHelena SaintKittsandNevis SaintLucia SaintMartin(Dutchpart) SaintMartin(Frenchpart) SaintPierreandMiquelon SaintVincentandtheGrenadines Samoa SanMarino SaudiArabia Senegal Serbia Seychelles SierraLeone Singapore Slovakia Slovenia SolomonIslands Somalia SouthAfrica SouthGeorgia/SandwichIslands SouthKorea SouthSudan Spain SriLanka Sudan Suriname SvalbardandJanMayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand Timor-Leste Togo Tokelau Tonga TrinidadandTobago Tunisia Turkey Turkmenistan TurksandCaicosIslands Tuvalu Uganda Ukraine UnitedArabEmirates UnitedKingdom(UK) UnitedStates(US)MinorOutlyingIslands UnitedStates(US)VirginIslands Uruguay Uzbekistan Vanuatu Vatican Venezuela Vietnam WallisandFutuna WesternSahara Yemen Zambia Zimbabwe Zip Company Phone Profession* SelectaProfession AcademiceducatorforHIM/HIT AddictionTreatmentSpecialist Administrator AdvancedPracticeNurse Audiologist Auditor Chiropractor Codingspecialist Complianceofficer Consumer Dentist Documentationspecialist EMT Geneticist HIM/HITstudent Librarian Nurse NursePractitioner Nutritionist OccupationalTherapist Office/Practicemanager Optometrist Organizationaleducator Pharmaceuticals/Biotech Pharmacist PhysicalTherapist Physician PhysicianAssistant Psychologist Reimbursementspecialist RespiratoryTherapist SocialWorker Speech-LanguagePathologist Student Specialty* SelectaSpecialty AddictionMedicine AllergyandImmunology Anesthesiology Cardiology CriticalCare Dentistry–General Dentistry–OralandMaxillofacial Dentistry–Orthodontics Dentistry–Pediatric Dentistry–Periodontics Dentistry–Prosthodontics Dermatology EmergencyMedicine Endocrinology FamilyPractice Gastroenterology Geriatrics Hematology Hepatology InfectiousDisease InternalMedicine Lipidologist MedicalGenetics Nephrology Neurology Nutrition ObstetricsandGynecology Oncology Ophthalmology Orthopedics Other Otolaryngology PainMedicine Pathology Pediatrics Pharmacy–Community Pharmacy–HealthSystems Pharmacy–Other PhysicalMedicineandRehabilitation Podiatry PreventiveMedicine Psychiatry Psychology Pulmonology Radiology Rheumatology SleepMedicine SportsMedicine Surgery–ColonandRectal Surgery–General Surgery–Neurological Surgery–Orthopedic Surgery–Pediatric Surgery–Plastic Surgery–Thoracic Surgery–Vascular Urology Women'sHealth Register *BysigningupIagreetotheprivacytermslistedhere × Close YourAccount Login Email Password Login ForgotPassword? × Close YourAccount ForgotPassword Email Emailnotfound.Pleasetryagainorregister. ResetPassword × Close YourAccount Login Email Password Login Register ForgotPassword? Register × Close Findthisquickreferenceguidehelpful? CreateaFREEaccount! UnlimitedAccesstoThousandsofSummaries HundredsofFreeMedicalCalculators PersonalizedContentRecommendationsandAlerts AccessSavedContentonAllMobileDevices SignupforFREE Alreadyamember?Login