肿瘤内科的疼痛管理

癌症相关疼痛的全球性Cancer-relatedpainisamajorissueofhealthcaresystemsworldwide.Thereportedincidence,consideringallstagesofthedisease,is51%,whichcanincreaseto90%intheadvancedandterminalstages.Foradvancedcancer,painismoderatetosevereinabout40–50%andverysevereorexcruciatingin25–30%ofcases.

疼痛治疗的现状在欧洲ArecentEuropeanstudythatfocusedontheprevalenceandtreatmentofcancerpainhasbeenperformedin11EuropeancountriesandIsraelin2006–2007.Atotalof5,084cancerpatientswerecontactedand56%(573)ofthemsufferedmoderatetoseverepainatleastmonthly.Theresultsofthissurveychallengethebeliefthatcancerpainisusuallywellmanaged.Thestudyfoundthatpainwasprincipallymanagedbymedicaloncologists(42%,242/573).Mostpatients(72%,415/573)reportedthattheirclinicianaskedthemabouttheirpaineitheratmostconsultations(16%,95/573)oreveryconsultation(55%,320/573).Only15%(88/573)ofpatientsreportedthattheirclinicianmeasuredtheirpainusingapainscale(55%,320/573).Of441patients,437reportedthattheyusedprescriptionmedicationstotreatpain.Amongthese,24%weretakingastepIIIopioidalone,12%weretakingastepIIopioidalone,7%weretakingstepIIandstepIIIopioids,eithertogetherorincombinationwithnon-opioiddrugs,and8%receivednon-opioidanalgesicsalone.Eventually,painwasdescribedasdistressingby67%ofpatients,asanintolerableaspectoftheircancerby36%,and32%reportedthatthepainwassobadtheywantedtodie.WHO癌症疼痛三阶梯治疗指南的目前的评价In1986theWorldHealthOrganization(WHO)publishedanalgesicguidelinesforthetreatmentofcancerpainbasedonathree-stepladderandpracticalrecommendations.TheWHOanalgesicladderremainstheclinicalmodelforpaintherapy.TheseandsimilardatasuggestthatadirectmovetothethirdstepoftheWHOanalgesicladderisfeasible.

WHO癌症疼痛三阶梯治疗指南的目前的评价Opioidsarethegold-standardtreatmentinmoderatetoseverepain.TheWorldHealthOrganization(WHO)in1986establishedastepwiseapproachforthetreatmentofpatientswithcancerpain.Thegoalwastoprovidetreatmentguidelinesthathealth-carepractitionerscouldeasilyfollow.NumerousstudieshaveshownthatwhentheWHOtreatmentguidelinesarefollowed,90%ofpatientsarepain-free.WHO癌症疼痛三阶梯治疗指南的目前的评价Thesepainmanagementguidelinessuggestthatthechoiceofanalgesicpharmacotherapyshouldbebasedontheintensityofpainreportedbythepatient,notsimplyonitsspecificetiology.IntheWHOguidelines,morphineremainsacornerstoneforthemanagementofcancerpain.Asubstantialminorityofpatientstreatedwithoralmorphine(10–30%)donothaveasuccessfuloutcomebecauseofexcessiveadverseeffects,inadequateanalgesia,oracombinationofbothadverseeffectstogetherwithinadequateanalgesia.Itisnowrecognizedthatindividualpatientsvarygreatlyintheirresponsetodifferentopioids.Patientswhoobtainpooranalgesicefficacyortolerabilitywithoneopioidwillfrequentlytolerateanotheropioid.Opioids,suchasmorphine,hydromorphone,oxycodone,fentanyl,andbuprenorphine,havebeenshowntobehighlyeffectiveinalleviatingmoderatetoseveremalignantpain.WHO癌症疼痛三阶梯治疗指南的目前的评价Recently,thedevelopmentofnewdrugsandformulationsofdifferentopioidshasenlargedtheavailabletherapeuticarsenalandimprovedtheiradministration,thuscontributingtobettertoleranceofsideeffects.Thishasmodifiedthethirdstepinanalgesia,andmorphinedoesnotremainthefirst-choicedrug.WHO癌症疼痛三阶梯治疗指南的目前的评价However,theroleoftheweakopioidsinthetreatmentofmoderatecancerpainhasbeenquestioned,andsomeexpertsspeculatethatthissecondstepoftheladdercouldbeomitted.MarinangeliF,CiccozziA,Leonardis

M,etal.Useofstrongopioidsinadvancedcancerpain:arandomizedtrial.JPainSymptomManage.2004;27:409–16.*Thisarticlespeculatesthatsecondstepoftheladdercouldbeomitted.

弱阿片类药物在二阶梯治疗中的地位受到质疑Whiletheuseofnon-opioidsforstepIand“strong”opioidsforstepIIIiswidelyaccepted,theclinicalusefulnessofthe“weak”opioidsinthemanagementofcancerpainhasbeenchallenged.Therearetwosystematicreviewscomparingtheefficacyofnonsteroidalanti-inflammatorydrugs(NSAID)versusaweakopioid.[1，2]TheresultssuggestthatthetransitionfromstepItostepIIdrugsdoesnotnecessarilyimproveanalgesia.Furthermore,thistransitionmaydelayachievingoptimalpaincontrol,especiallyinpatientswithrapidlyprogressivepainorinthosewhoneedquicktitrationofanalgesictherapy.1.EisenbergE,BerkeyCS,CarrDB,MostellerF,ChalmersTC.Efficacyandsafetyofnonsteroidalantiinflammatorydrugsforcancerpain:ameta-analysis.JClinOncol.1994;12:2756–65.2.McNicolE,StrasselsS,GoudasL,LauJ,CarrD.Nonsteroidalanti-inflammatorydrugs,aloneorcombinedwithopioids,forcancerpain:asystematicreview.JClin

Oncol.2004;22:1975–92.强阿片类药物一线治疗疼痛的临床试验Theefficacyandtolerabilityofstrongopioidsasfirst-linetreatmentcomparedwiththerecommendedWHOregimenwasanalyzedinaphaseIIIstudyperformedin100terminalcancerpatientswhosufferedfrommildtomoderatepain.Patientswhowerestartedonstrongopioidsnotonlyhadsignificantlybetterpainrelief,buttheyalsorequiredsignificantlyfewerchangesintherapy,hadgreaterreductionsinpainwhentherapeuticchangeswereinitiated,andreportedgreatersatisfactionwithtreatment.Nodifferenceswereobservedinqualityoflifeorperformancestatusbetweenthetwogroups.Thesedatasuggesttheutilityofstrongopioidsforfirst-linetreatmentofpaininpatientswithterminalcancer.[1]

1.MarinangeliF,CiccozziA,LeonardisM,etal.Useofstrongopioidsinadvancedcancerpain:arandomizedtrial.JPainSymptomManage.2004;27:409–16.疼痛视觉量表评分>5是治疗的关键Experiencereportedsinceitsapplicationmorethan20yearsago,aswellasthedeeperunderstandingofthedifferenttypesofpainandthereleaseofbrandnewtherapeuticformulations,havecurrentlyledustoconsidernewchangesinthisuniqueanalgesictreatmentmodel,thususefulinchoosingthebesttherapyaccordingtothetypeofpainandnotonlyitsseverity.Asaresult,someexpertssuggestthe"analgesicelevator"model.Incontrasttotheladderconcept,thismodelleadsustotheconceptofimmediateresponse,sincethetransportofanalgesicsinsidealiftwouldbequickerthansteppingupaladder.ThishighlightshowimportantitistoperformacontinuousevaluationforpainbasedonthePainVisualAnalogSeverityScale(PVASS).Infact,ascore>5onthisscaleshouldmakeusbealertandprovidethelevelofanalgesiarequiredimmediately.TorresLM,CalderónE,PerniaA,Martínez-VázquezJ.[Fromthestairstotheescalator].RevSocEspDolor.2002;9:289–90.MorphineWeschulesDJ,BainKT,ReifsnyderJ,etal.Towardevidence-basedprescribingatendoflife:acomparativeanalysisofsustained-releasemorphine,oxycodone,andtransdermal

fentanyl,withpain,constipation,andcaregiverinteractionoutcomesinhospicepatients.PainMed.2006;7:320–9.FentanylFentanylFentanylisrecommendedforpatientswhoseopioidrequirementsarestableatalevelcorrespondingto≥60mg/dayofmorphine.JostL,RoilaF.ESMOGuidelinesWorkingGroup.Managementofcancerpain:ESMOClinicalRecommendations.AnnOncol.2008;19(Suppl2):ii119–21.TransdermalFentanylTTSOncethepatchisplaced,fentanylserumlevelsincreaseuptoanalgesicconcentrationsin6–12hours,remainingstablefrom12–24hoursanddecreasingduringthefollowing48hours.Onesingleadministrationevery72hoursreachesstableserumfentanyllevels.Afterremovingthepatch,serumlevelsoffentanylprogressivelydecreaseuntil50%in17hours.Itsbioavailabilityis92%,andthereleasedamountofthedrugcorrelateswiththesizeofthepatch.OraltransmucosalfentanylcitrateFentanylIontophoreticTransdermalSystem

FentanylSublingualTablet

Fentanylcitratenasalspray,TAIFUN®.Oxycodonefirst-stepmetabolizationinliver,whichexplainsits60–87%bioavailability.Oxycodoneserumhalf-lifetimeisdoublethatofmorphine(3–5hours)andreachesstationaryconcentrationsin24–36hours.Oxycodoneinteractswithseveralmedications,includingselectiveserotoninreuptakeinhibitors,cyclosporine,andrifampin.SelectiveserotoninreuptakeinhibitorsinhibitoxycodonemetabolismbyCYP450,whichleadstohigherconcentrationsandincreasedtoxicity.Oxycodonecomparisonbetweenoxycodoneandmorphineincombinationversusmorphinealoneandprovedthattheconcomitantadministrationexhibitedabetteranalgesiaprofileandlessincidenceofemesis.LaurettiGR,OliveiraGM,PereiraNL.Comparisonofsustained-releasemorphinewithsustained-releaseoxycodoneinadvancedcancerpatients.BrJCancer.2003;89:2027–30.OxycodoneOncancerchronicpain,fiveclinicaltrialshavebeenpublishedcomparingcontrolled-releaseoxycodoneversuscontrolled-releasemorphine(fourtrials)andversushydromorphone(onestudy).Themainefficacyendpointwastheperceptionofpainreportedbypatientsthemselves,measuredasascoreonPVASSorastheamountofrescuemedicationneeded.Nosignificantdifferencesinefficacywereproven,butinasinglestudy[56]resultsweremorefavorabletomorphine.Ingeneral,thelimitednumberofpatientsrecruitedmakesthesestudiesdifficulttoevaluateproperly.Theirimportance,ontheotherhand,liesinthefactthatthesestudieshelpeddetermineequianalgesicdoses.Thus,intermsofequianalgesicefficacy,1mgoxycodonedosecorrespondsto1.5mgofmorphine,[55–58]whereasone1mgoxycodonedosecorrespondsto0.25mgofhydromorphone.[59]

ThematchofoxycodoneandnaloxoneAgonistAntagonistNaloxoneOxycodoneTargin@

OxycodoneNaloxone

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TheinnovativeprincipleAchievingpotentanalgesia;Treatmentand/orprophylaxisofopioidinducedconstipation;Improvedqualityoflifeandcompliance.innovative总结我国肿瘤病人疼痛处理中问题现状1.管理上较为严格，有需要的病人不能合理或及时的得到相应的符合标准的处理。2.病人家属及病人自己的问题，不愿意及时使用强阿片类药物。3.病人的经济问题。4.药物品种的缺少。尤其在基层医院。5.病人的教育。6.医务人员对肿瘤病人疼痛的不作为。7.药品企业对疼痛产品开发的不足。8.缺少相应的符合国情的疼痛治疗指南。9.对于难治性疼痛缺少共识。10.缺少专业的队伍，包括心理，护士和专科医生。管理上较为严格，有需要的病人不能合理或及时的得到相应的符合标准的处理。1.由于国家政策的限制，现行的麻醉药品管理较为严格。2.表现为：1.病人用药量有限制2.针剂控制3.药品品种不全，剂量不全4.地域差异明显5.处方医生限制病人家属及病人自己的问题，不愿意及时使用强阿片类药物1.由于历史原因，国人对于使用阿片类药物有一事实上的恐惧心理，不愿过早使用此类药物。2.缺少相应的宣传教育机制。3.缺少心理辅导机制。4.对于阿片类药物的副作用的夸大。5.对于使用针剂的误区，尤其在基层医院。病人的经济问题1.由于药品的价格较高，病人往往需要长期使用，没有医保或就是有医保病人的经济负担仍然较重。2.对于没有报销来源的病人，长期的治疗疼痛的药物根本负担不起。3.这也是造成国内目前为止杜冷丁仍然有很多医院仍在使用的主要问题。4.肿瘤病人的疼痛问题作为一个人道的问题