Opioids and Respiratory Depression -...
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OpioidsandRespiratoryDepression
ClinicalCommitteeSocietyofAnesthesiaandSleepMedicine
https://commons.wikimedia.org/wiki/File:Mu_opioid_receptor.svg
Introduction• Opioid-inducedrespiratorydepression(OIRD)isprobablythemostlimitingsideeffectofopioidanalgesics
• Erringoneithersideofachievingoptimalanalgesiaoravoidingrespiratorydepressioncanresulteitherinrespiratorydepressionorsuboptimalanalgesia
• Chronicopioiduseisestimatedtocause1/3ofcasesofcentralsleepapnea(CSA)
• OIRDcanresultinperioperativemorbidityandmortality,particularlyinhighriskpatients
• Appropriatemonitoringandrescuemeasures,useofopioidadjunctsandalternatives,aswellasspecialprecautionsinhighriskpatientscanminimizeOIRDimpact
Outline
• Analgesiceffects• Respiratorydepressanteffects• PerioperativeIssues
• Alternativestoopioids
• Highriskpatientpopulations
OpioidsandPain• Opioidsarecommonlyusedforbothacuteandchronicpainmanagement
• Painisasubjectiveexperience• Inadequatepainmanagementcanleadtoadverseoutcomes• Longerhospitalizationandrehabilitation• Cardiopulmonarymorbidity• Readmissions• Increasedcosts• Developmentofhyperalgesiaorcomplexregionalpainsyndrome
Lovich-SapolaJetal.SurgClin NorthAm2015;95:301Nealetal.Reg Anesth PainMed2015;40:401
OpioidsAnalgesicEffects• Opioidreceptors-G-proteincoupledreceptors
• Opioidsystemmediates• Pain• Respiratorycontrol• Stressresponse• Thermoregulation
ChapmanJ,LalkhenA.AnaesthIntCare2016;17(3):144
OpioidsandPain
Paintransmissionmodulatedatanumberoflevels,includingthedorsalhornofthespinalcordandviadescendinginhibitorypathways. Descendingpathwaysoriginateinthe somatosensorycortex andthe hypothalamus.Thalamicneuronsdescendtothemidbrain.There,theysynapseonascendingpathwaysinthemedullaandspinalcordandinhibitascending nerve signals.Thiscanbealocationofactionofopioidsinpainrelief.
PowerPoint(Office2010)[ComputerSoftware].Redmond,WA:Microsoft
OpioidsRespiratoryEffects• Brainstem’spre-Botzingercomplex(pre-BotC)generatesrespiratoryrhythm• Opioidreceptorsarealsofoundininspiratorygeneratingpre-BotC• Thoughttobepartofcauseofopioid-inducedrespiratorydepression
• Opioidreceptorsarefoundinbothcentralandperipheralnervoussystem
OpioidsRespiratoryEffects• Suppressrespiratoryrate,tidalvolume,andminuteventilation
• Decreaseresponsivenesstobothhypercapniaandhypoxia
• Opioid-relatedsleephypoventilationmayberelatedtoeffectsatpre-BotCandhypoglossalnerve(increasedupperairwayobstruction)
AroraNetalSleepMedClin2014;9
Opioids:Concerns• Addressingpaintoimprovepatientsatisfactionhasincreaseduseofopioids
• Practitionersprescribingopioidsmaynotbeawareofconcerns
• TheJointCommission(TJC)hasissuedalerton“SafeUseofOpioidsinHospitals”• Recommendimprovedpatientsassessment to decreaseriskofopioidoverdose
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm518697.htm
Checklist for prescribing opioids for chronic pain
https://www.cdc.gov/drugoverdose/prescribing/resources.html
Checklist for prescribing opioids for chronic pain
https://www.cdc.gov/drugoverdose/prescribing/resources.html
Referencesforproviders
https://www.cdc.gov/drugoverdose/prescribing/resources.html
Opioids:TJCAlert• Mostcommoncausesofopioid-relatedadverseevents• Wrongdosemedicationerror(47%)• Impropermonitoring(29%)
Opioids:TJCAlert• Associatedpatientcharacteristics• Sleepapneaorsleepdisorder• MorbidobesitywithhighriskofOSA• Snoring• Age>40• Upperabdominalorthoracicsurgery• Highopioidrequirementorhabituation• Othersedatingdrugs• Pulmonary,cardiacdiseaseorsmoking
Opioids:Neuraxial• Neuraxialinvolvesintrathecalorepiduraladministrationofmedication
• OSApatientsreceivingperioperativeneuraxialopioids(n=121)• 6(5%)hadpost-operativeopioid-inducedrespiratorydepression(OIRD)• 5werereceivingcontinuousfentanyl-containingepiduralinfusionswithoutconcurrentPAPtherapy• 3resultedindeath
OrlovD.JClin Anesth 2013;25:591-9MayoClinic,2011
NeuraxialOpioids:ASA• Allpatientsshouldbemonitoredforadequacyofventilation,oxygenation,andlevelofconsciousness• Increasedmonitoring forhigh-risk:• Unstablemedicalconditionsuchas• Congestiveheartfailure• SevereCOPD
• Obesity• OSA• Systemicopioidsorsedatives• Extremesofage Anesthesiology2016;124(3):535-552
NeuraxialOpioids:ASA• AdministersupplementalO2 topatientswithalteredlevelofconsciousness,respiratorydepression,orhypoxia
• Ensureuseofpre-existingPAPintheperioperativeperiod
• Methodstodetectrespiratorydepression• Oxygensaturation• Carbondioxidelevel• Levelofsedation
• Haveresuscitativemeasuresavailable:• Reversalagents• Noninvasivepositivepressureventilation(NPPV)
Anesthesiology2016;124(3):535-552
PostoperativeOIRD:AnesthesiaPatientSafetyFoundation(APSF)
• Allpatientsreceivingpostoperativeopioidanalgesia,shouldhave:• Periodicassessmentofconsciousness• Continuousmonitoringofoxygenationbypulseoximetry(SpO2)• Highriskpatientsshouldhavecontinuousobservationofpulseoximetry1
• Continuousmonitoringofventilationbycapnography(etCO2)orequivalentmethodrecentlyencouraged2
1.Weinger MB,APSFNewsletter2011;26(2):212.GeralemouSetalAPSFNewsletter2016;31(2):42-43
PostoperativeOIRD:ASAClosedClaimProject(CCP)
• 1990-2009,357acutepainclaims,92POIRDcases
• Patientdemographics:• 25%hadOSA(16%)orhighrisk(9%)• 47%obese• 45%ASAPSscore≥3• 8%historyofchronicopioiduse
LeeLA.Anesthesiology.2015;122:659
PostoperativeOIRD:ASACCP• Outcome:• 55%resultedindeath• 22%resultedinpermanentbraindamage
• Causality:• 89%judgedpreventablebybettermonitoring(probably43%,possibly46%)
LeeLA.Anesthesiology.2015;122:659
PostoperativeOIRD:ASACCP
Concurrentfactors:• 58%hadnorespiratorymonitoring• 67%hadnopulseoximetrymonitoring• 85%hadnosupplementaloxygen• 34%hadconcurrentsedativeagent• 33%hadmultipleprescribers• 31%hadinadequatenursingassessmentorresponse
PostoperativeOIRD:ASACCP
• Timeframe:• 88%duringfirstpostoperativeday• 62%weresomnolentbeforetheevent• TimebetweenlastnursingcheckanddiscoveryofpostoperativeOIRD:minutestohours
LeeLA.Anesthesiology.2015;122:659
AlternativestoOpioids• Useofothermedicationsandtechniques
• Regionalanalgesia• Usinglocalanesthetictoblockconductionofpainoveraspecificarea
• Continuousregionaltechniquesdependingontypeofsurgery• Orthopedicsurgery• Thoracicsurgery
Alternatives:Interventions• Non-pharmacologictechniques• Cognitiveoptionssuchasguidedimageryandmusiccanbeconsidered• Transcutaneouselectricalnervestimulation(TENS)atincisionsite
ChouRetalJPain2016;17(2):131
Alternatives:Regional• Regionalanesthesia(RA)canreduceneedforsystemicanalgesics
• Singledoseperipheralnerveblock(PNB)canbeutilizedformultipleprocedures• Orthopedicandabdominalprocedures
• Continuoustechniquescanbeconsideredfor• Orthopedicproceduressuchaship,knee,andshouldersurgery
• ThoracicEpiduralforthoracicsurgery• Epiduralforupperabdominalsurgery
Alternatives:Regional• PNBsdecreasedperioperativecomplicationsintotalhiporkneearthroplasty1
• PNBsimproveanalgesiaanddecreaseanalgesicrequirements2
• ASArecommendsconsideringtheuseofregionaltechniqueswhen surgicaltype/siteisappropriate3
1.MemtsoudisetalReg Anesth PainMed2013;38(4):2742.RichmanJMetalAnesth Analg 2006;102(1):2483.ASATaskForce,Anesthesiology2014;120(2):268
MultimodalAnalgesia
MayoClinic,2017
Alternatives:Multimodal• Acetaminophen• Nonspecificcentralcyclooxygenaseinhibitor.• Lowtoxicityexceptforsevereliverdysfunction
• Nonsteroidalanti-inflammatorydrugs• Inhibitcyclooxygenaseenzymes• Ketorolac,celecoxibcommonlyused• Concernwithrenaldysfunction,cardiovascularischemia,GIbleedingandulceration
Alternatives:Multimodal• Tramadol• Weakopioidagonist,lessrespiratoryeffects• Cautionwithrenaldysfunctionorseizures
• Gabapentinoids(gabapentinandpregabalin)• Cautionwithrenaldysfunction• Mildlysedating
• Ketamine• ActivatesNMDAreceptorsinCNSandperipherally• Maycausedissociativesymptoms
Alternatives:Multimodal
• Lidocaineintravenous(IV)infusion• Usedinopenandlaparoscopicabdominalsurgery
• Cautionforlidocainetoxicity• Liposomalbupivacaine• Surgicalsiteinfiltrationwithextendedreleasebupivacaine
• Candecreaseneedforopioidspostoperatively
ViscusiERetalClinJPain2014;30(2):102
HighRiskPatients• Elderlypatients(age>65years)• Knownorsuspectedsleepdisorderedbreathing
• Administrationofmultiplesedativeagents
• Hypermetabolizers• Variationsinactivityofcytochromep450enzymesystemsmayleadtohigherlevelsofactiveopioids
Benini F,etal.ItalJPediatr 2014;40:16
Elderly
https://commons.wikimedia.org/wiki/File:Sweden_road_sign_-_Elderly.svg
HighRisk:Elderly• Elderlypatientsareathighriskforadverseeffectsofanalgesics
• Declineinorganfunctionwithageleadstoincreasedsensitivitytomedications
• Cognitiveimpairmentdoesnotdecreasepainperceptionthresholds
• Multiplemedicationsincreasetheriskofadversedrugreaction
McKeownJLAnesthesiol Clin2015;33:563
HighRisk:Elderly• Opioidsrelyonliverformetabolism
• Morphinehasmultipleactivemetabolitesthataccumulateinrenaldysfunction
• Creatininemaynotreflecttruerenalfunction,aselderlymayhavedecreaseinmusclemass
• Opioidswithfewactivemetabolitesarebestifopioidsneeded
HighRisk:Elderly• Elderlyaremoresensitivetosideeffectsincludingrespiratorydepression,sedation,andcognitivechanges
• Avoidcontinuousinfusionsifpossible• Decreaseinitialopioiddosebyhalfwithpatientcontrolledanalgesia(PCA)
• Anticholinergicmedicationsincreasetheriskofdelirium(meperidine)
SleepDisorderedBreathing
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HighRisk:SleepDisorderedBreathing(SDB)
• SDBisfoundinupto25%ofsurgicalpatients
• Opioidsaffectrespiratorycontrol,andmayworsenOSAandobesityhypoventilationsyndromeintheperioperativeperiod
• AsystematicreviewshowedassociationofOSAwithpostoperativecomplications
OppererMetalAnesth Analg 2016;122(5):1321
HighRisk:SDB• OptimaltoidentifySDBpriortosurgery• PreOp screeningtools,includingSTOP-BANG,shouldbeutilized• IdentifythosewithahighlikelihoodSDB
• Ensureuseofpre-existingPAPpostOp• Utilizeopioidalternatives• Regionaltechniquesifpossible• Multimodalanalgesicregimen
HighRisk:Sedatives• Non-opioidsedativesincreaserespiratorydepression• Includesbenzodiazepines,musclerelaxants,sleepenhancingmedications• Sedatingantiemeticssuchaspromethazinecancontributetothis
SubramanyamRetal,Pediatr Anaesth 2014;24(4):412
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HighRisk:Hypermetabolizers• Severalopioids(codeine,morphine,hydrocodone)produceactivemetabolites
• Certainpatientsmaymetabolizethesemedicationsdifferentlyandareconsideredrapidorhypermetabolizers
• Thesepatientsmayexperienceincreasedseverityofrespiratorydepressionandhaveincreasedriskofcomplicationsfromadministrationoftheseopioids
SmithHS.MayoClin Proc2009;84(7):613Benini F,Barbi E.ItalJPediatr 2014;40:16
Case182yearoldpatientwithpriorgoodfunctionality,withHTNandCOPDwasadmittedwithahipfracture.NohistoryofCKD,butCreatinineatadmissionwas1.4,GFRof37.
Within8hoursofadmissionhereceived5mgofMorphineivx2timesandonedoseof2mgofDilaudid.
Hewasfoundinthebedlethargicwithshallowbreathingbyhisfamily.Arapidresponseteamwascalled;
Oxygensaturationwas70%.Hereceivednaloxone0.4mgandregainedconsciousness
Hewasstartedonnon-invasiveventilation.AnABGshowedpH7.28,pCO2 of58mmHgandPO2 of50mmHg.
Case1• Issue• ElderlypatientwithreducedrenalfunctionandCOPDreceivedalargedoseofopioidswithoutbeingappropriatelymonitored.
• Intervention• Narcan andnoninvasiveventilation.Transfertoahigherlevelofcare
Case245yearoldmalewitharecentdiagnosisofOSApresentedtotheemergencyroom(ER)afteramotorvehicleaccidentwithlegtrauma.OxygendesaturationwasnotedintheERafterIVmorphinewasgivenforpain,andthepatientrequiredmaskventilation.
Thepatientthenunderwentgeneralanesthesiaforanopenreductionandinternalfixation(ORIF)ofatibialfracture.ApneicepisodeswerenotedinthePACUwithdesaturationsinthe80%range.
Thepatientwassenttothefloorwitharequestforcontinuouspulseoximetry.Continuouspulseoximetrywasnotapplied,andfurtherapneicepisodesweredocumentedbythenurses.
After30minutes,thepatientwasfoundincardiopulmonaryarrest.ThepatientwasintubatedandCPRwasperformeduntilspontaneousrespirationsreturned.Severeanoxicneurologicinjuryresultedandthepatientsubsequentlydied.
Case2• Issue• PrematurereleasefromthePACUaftergeneralanesthesiainapatientwithknownOSA.
• FailuretomonitorapatientwithknownOSAgivenIVopioidspostoperativelydespitedocumentedapneasanddesaturationwhilereceivingopioids.
• Outcome• Severeanoxicneurologicinjuryanddeath.
Conclusion• PostoperativeOIRDisaclinicalchallengewithwideandsignificantimpactthatrepresentsapublichealthchallenge
• OIRDisaconcernforpatients,healthcareproviders,accreditingagencies,publichealthprofessionals,healthpolicymakers,andmedicalprofessionalorganizations
• ResearchandknowledgedisseminationamongallstakeholderstodevelopbestpracticesaboutOIRDcanmitigateitsimpact
• SASMcanplayakeyroleinthisprocess