Opioids and Respiratory Depression - SASMsasmhq.org/.../uploads/2018/03/Opioids-and-Respiratory-Depression.… · Opioids and Pain •Opioids are commonly used for both acute and

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


Referencesforproviders


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%)


PostoperativeOIRD:ASACCP

Concurrentfactors:• 58%hadnorespiratorymonitoring• 67%hadnopulseoximetrymonitoring• 85%hadnosupplementaloxygen• 34%hadconcurrentsedativeagent• 33%hadmultipleprescribers• 31%hadinadequatenursingassessmentorresponse

PostoperativeOIRD:ASACCP

• Timeframe:• 88%duringfirstpostoperativeday• 62%weresomnolentbeforetheevent• TimebetweenlastnursingcheckanddiscoveryofpostoperativeOIRD:minutestohours


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

https://commons.wikimedia.org/wiki/File:DEA_to_host_national_prescription_drug_take-back_160324-F-HC995-002.jpg

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

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