肿瘤内科的疼痛管理专家讲座.pptx

肿瘤内科疼痛管理现实状况和对策肿瘤内科的疼痛管理第1页癌症相关疼痛全球性Cancer-related pain is a major issue of healthcare systems worldwide.The reported incidence,considering all stages of the disease,is 51%,which can increase to 90%in the advanced and terminal stages.For advanced cancer,pain is moderate to severe in about 4050%and very severe or excruciating in 2530%of cases.肿瘤内科的疼痛管理第2页疼痛治疗现实状况在欧洲A recent European study that focused on the prevalence and treatment of cancer pain has been performed in 11 European countries and Israel in.A total of 5,084 cancer patients were contacted and 56%(573)of them suffered moderate to severe pain at least monthly.The results of this survey challenge the belief that cancer pain is usually well managed.The study found that pain was principally managed by medical oncologists(42%,242/573).Most patients(72%,415/573)reported that their clinician asked them about their pain either at most consultations(16%,95/573)or every consultation(55%,320/573).Only 15%(88/573)of patients reported that their clinician measured their pain using a pain scale(55%,320/573).Of 441 patients,437 reported that they used prescription medications to treat pain.Among these,24%were taking a step III opioid alone,12%were taking a step II opioid alone,7%were taking step II and step III opioids,either together or in combination with non-opioid drugs,and 8%received non-opioid analgesics alone.Eventually,pain was described as distressing by 67%of patients,as an intolerable aspect of their cancer by 36%,and 32%reported that the pain was so bad they wanted to die.Breivik H,Cherny N,Collett B,et al.Cancer-related pain:a pan-European survey of prevalence,treatment,and patient attitudes.Ann Oncol.;26 Epub ahead of print*The most recent study of the prevalence and management of cancer pain in Europe and I srael that demonstrates that at the moment the treatment of cancer pain is suboptimal.肿瘤内科的疼痛管理第3页WHO癌症疼痛三阶梯治疗指南当前评价In 1986 the World Health Organization(WHO)published analgesic guidelines for the treatment of cancer pain based on a three-step ladder and practical recommendations.The WHO analgesic ladder remains the clinical model for pain therapy.These and similar data suggest that a direct move to the third step of the WHO analgesic ladder is feasible.肿瘤内科的疼痛管理第4页WHO癌症疼痛三阶梯治疗指南当前评价Opioids are the gold-standard treatment in moderate to severe pain.The World Health Organization(WHO)in 1986 established a stepwise approach for the treatment of patients with cancer pain.The goal was to provide treatment guidelines that health-care practitioners could easily follow.Numerous studies have shown that when the WHO treatment guidelines are followed,90%of patients are pain-free.肿瘤内科的疼痛管理第5页WHO癌症疼痛三阶梯治疗指南当前评价 These pain management guidelines suggest that the choice of analgesic pharmacotherapy should be based on the intensity of pain reported by the patient,not simply on its specific etiology.In the WHO guidelines,morphine remains a cornerstone for the management of cancer pain.A substantial minority of patients treated with oral morphine(1030%)do not have a successful outcome because of excessive adverse effects,inadequate analgesia,or a combination of both adverse effects together with inadequate analgesia.It is now recognized that individual patients vary greatly in their response to different opioids.Patients who obtain poor analgesic efficacy or tolerability with one opioid will frequently tolerate another opioid.Opioids,such as morphine,hydromorphone,oxycodone,fentanyl,and buprenorphine,have been shown to be highly effective in alleviating moderate to severe malignant pain.肿瘤内科的疼痛管理第6页WHO癌症疼痛三阶梯治疗指南当前评价Recently,the development of new drugs and formulations of different opioids has enlarged the available therapeutic arsenal and improved their administration,thus contributing to better tolerance of side effects.This has modified the third step in analgesia,and morphine does not remain the first-choice drug.肿瘤内科的疼痛管理第7页WHO癌症疼痛三阶梯治疗指南当前评价However,the role of the weak opioids in the treatment of moderate cancer pain has been questioned,and some experts speculate that this second step of the ladder could be omitted.Marinangeli F,Ciccozzi A,Leonardis M,et al.Use of strong opioids in advanced cancer pain:a randomized trial.J Pain Symptom Manage.;27:40916.*This article speculates that second step of the ladder could be omitted.肿瘤内科的疼痛管理第8页弱阿片类药品在二阶梯治疗中地位受到质疑While the use of non-opioids for step I and“strong”opioids for step III is widely accepted,the clinical usefulness of the“weak”opioids in the management of cancer pain has been challenged.There are two systematic reviews comparing the efficacy of non steroidal anti-inflammatory drugs(NSAID)versus a weak opioid.1，2 The results suggest that the transition from step I to step II drugs does not necessarily improve analgesia.Furthermore,this transition may delay achieving optimal pain control,especially in patients with rapidly progressive pain or in those who need quick titration of analgesic therapy.1.Eisenberg E,Berkey CS,Carr DB,Mosteller F,Chalmers TC.Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain:a meta-analysis.J Clin Oncol.1994;12:275665.2.McNicol E,Strassels S,Goudas L,Lau J,Carr D.Nonsteroidal anti-inflammatory drugs,alone or combined with opioids,for cancer pain:a systematic review.J Clin Oncol.;22:197592.肿瘤内科的疼痛管理第9页强阿片类药品一线治疗疼痛临床试验The efficacy and tolerability of strong opioids as first-line treatment compared with the recommended WHO regimen was analyzed in a phase III study performed in 100 terminal cancer patients who suffered from mild to moderate pain.Patients who were started on strong opioids not only had significantly better pain relief,but they also required significantly fewer changes in therapy,had greater reductions in pain when therapeutic changes were initiated,and reported greater satisfaction with treatment.No differences were observed in quality of life or performance status between the two groups.These data suggest the utility of strong opioids for first-line treatment of pain in patients with terminal cancer.1 1.Marinangeli F,Ciccozzi A,Leonardis M,et al.Use of strong opioids in advanced cancer pain:a randomized trial.J Pain Symptom Manage.;27:40916.肿瘤内科的疼痛管理第10页疼痛视觉量表评分5是治疗关键Experience reported since its application more than 20 years ago,as well as the deeper understanding of the different types of pain and the release of brand new therapeutic formulations,have currently led us to consider new changes in this unique analgesic treatment model,thus useful in choosing the best therapy according to the type of pain and not only its severity.As a result,some experts suggest the analgesic elevator model.In contrast to the ladder concept,this model leads us to the concept of immediate response,since the transport of analgesics inside a lift would be quicker than stepping up a ladder.This highlights how important it is to perform a continuous evaluation for pain based on the Pain Visual Analog Severity Scale(PVASS).In fact,a score 5 on this scale should make us be alert and provide the level of analgesia required immediately.Torres L M,Caldern E,Pernia A,Martnez-Vzquez J.From the stairs to the escalator.Rev Soc Esp Dolor.;9:28990.肿瘤内科的疼痛管理第11页MorphineDoses need to be individualizedbioavailability is variable(1565%)Serum levels have a peak at approximately one hour.Clearance is variable and medium elimination half-life ranges from 34 hours(17).This determines the way of administration.Comparative clinical studies have shown no difference among the different types of opioids available in terms of symptom control and side effects.One retrospective cohort study including 12,000 patients compared efficacy and adverse events among transdermal fentanyl,controlled/extended-release morphine,and oxycodone,finding no difference either in pain control or in the gastrointestinal side-effect profile.Weschules DJ,Bain KT,Reifsnyder J,et al.Toward evidence-based prescribing at end of life:a comparative analysis of sustained-release morphine,oxycodone,and transdermal fentanyl,with pain,constipation,and caregiver interaction outcomes in hospice patients.Pain Med.;7:3209.肿瘤内科的疼痛管理第12页FentanylFentanyl is a selective-receptor agonist.Compared to morphine,it is approximately 100-times more potent,1,000-times more lipophilic,and it features a lower molecular weight.Fentanyl is metabolized primarily in the liver.In humans,in vitro experiments have demonstrated that fentanyl is metabolized mainly by cytochrome P450 3A4(CYP3A4)to nor-fentanyl via oxidative N-dealkylation.Its clearance half-life is short and the effect of a single oral dose lasts for 30 minutes.26 Oral(enteral)bioavailability of fentanyl is poor and hence the usual routes of administration are intravenous,subcutaneous,spinal,transdermal,and transmucosal.肿瘤内科的疼痛管理第13页FentanylFentanyl is recommended for patients whose opioid requirements are stable at a level corresponding to 60 mg/day of morphine.Jost L,Roila F.ESMO Guidelines Working Group.Management of cancer pain:ESMO Clinical Recommendations.Ann Oncol.;19(Suppl 2):ii11921.肿瘤内科的疼痛管理第14页Transdermal Fentanyl TTSOnce the patch is placed,fentanyl serum levels increase up to analgesic concentrations in 612 hours,remaining stable from 1224 hours and decreasing during the following 48 hours.One single administration every 72 hours reaches stable serum fentanyl levels.After removing the patch,serum levels of fentanyl progressively decrease until 50%in 17 hours.Its bioavailability is 92%,and the released amount of the drug correlates with the size of the patch.肿瘤内科的疼痛管理第15页Oral transmucosal fentanyl citrateFentanyl Iontophoretic Transdermal System Fentanyl Sublingual Tablet 肿瘤内科的疼痛管理第16页Fentanyl citrate nasal spray,TAIFUN.肿瘤内科的疼痛管理第17页Oxycodonefirst-step metabolization in liver,which explains its 6087%bioavailability.Oxycodone serum half-life time is double that of morphine(35 hours)and reaches stationary concentrations in 2436 hours.Oxycodone interacts with several medications,including selective serotonin reuptake inhibitors,cyclosporine,and rifampin.Selective serotonin reuptake inhibitors inhibit oxycodone metabolism by CYP450,which leads to higher concentrations and increased toxicity.肿瘤内科的疼痛管理第18页Oxycodonecomparison between oxycodone and morphine in combination versus morphine alone and proved that the concomitant administration exhibited a better analgesia profile and less incidence of emesis.Lauretti GR,Oliveira GM,Pereira NL.Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients.Br J Cancer.;89:202730.肿瘤内科的疼痛管理第19页OxycodoneOn cancer chronic pain,five clinical trials have been published comparing controlled-release oxycodone versus controlled-release morphine(four trials)and versus hydromorphone(one study).The main efficacy endpoint was the perception of pain reported by patients themselves,measured as a score on PVASS or as the amount of rescue medication needed.No significant differences in efficacy were proven,but in a single study56 results were more favorable to morphine.In general,the limited number of patients recruited makes these studies difficult to evaluate properly.Their importance,on the other hand,lies in the fact that these studies helped determine equianalgesic doses.Thus,in terms of equianalgesic efficacy,1 mg oxycodone dose corresponds to 1.5 mg of morphine,5558 whereas one 1 mg oxycodone dose corresponds to 0.25 mg of hydromorphone.59 肿瘤内科的疼痛管理第20页The match of oxycodone and naloxoneAgonistAntagonistNaloxoneOxycodoneTargin 肿瘤内科的疼痛管理第21页OxycodoneNaloxoneTargin The innovative principle Achieving potent analgesia;Treatment and/or prophylaxis of opioid induced constipation;Improved quality of life and compliance.肿瘤内科的疼痛管理第22页innovative肿瘤内科的疼痛管理第23页肿瘤内科的疼痛管理第24页肿瘤内科的疼痛管理第25页肿瘤内科的疼痛管理第26页肿瘤内科的疼痛管理第27页肿瘤内科的疼痛管理第28页总结Since 1986,the application of the WHO stepladder analgesic regimen has allowed a better control of pain and will achieve pain relief in the majority of patients with cancer.Between 7090%of patients with cancer pain treated according to the three-step ladder achieves effective analgesia.Experience reported since its application more than 20 years ago suggests the utility of strong opioids for first-line treatment of pain in patients with terminal cancer could be better,especially for patients with moderate to severe cancer pain.Recent updates about the prevalence and treatment of cancer pain in Europe have demonstrated that assessment is poor and treatment and outcomes are often suboptimal.It is necessary to improve pain management in moderate to severe cancer pain.Opioids are the gold-standard treatment in moderate to severe pain and in the WHO guidelines;morphine remains a cornerstone for the management of cancer pain.Recently,the development of new drugs and formulations of different opioids has enlarged the available therapeutic arsenal,modifying the third-step in analgesia and morphine is not the only option.肿瘤内科的疼痛管理第29页肿瘤内科的疼痛管理第30页我国肿瘤病人疼痛处理中问题现实状况1.管理上较为严格，有需要病人不能合理或及时得到对应符合标准处理。2.病人家眷及病人自己问题，不愿意及时使用强阿片类药品。3.病人经济问题。4.药品品种缺乏。尤其在基层医院。5.病人教育。6.医务人员对肿瘤病人疼痛不作为。7.药品企业对疼痛产品开发不足。8.缺乏对应符合国情疼痛治疗指南。9.对于难治性疼痛缺乏共识。10.缺乏专业队伍，包含心理，护士和专科医生。肿瘤内科的疼痛管理第31页管理上较为严格，有需要病人不能合理或及时得到对应符合标准处理。1.因为国家政策限制，现行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.地域差异显著5.处方医生限制肿瘤内科的疼痛管理第32页病人家眷及病人自己问题，不愿意及时使用强阿片类药品1.因为历史原因，国人对于使用阿片类药品有一实际上恐惧心理，不愿过早使用这类药品。2.缺乏对应宣传教育机制。3.缺乏心理辅导机制。4.对于阿片类药品副作用夸大。5.对于使用针剂误区，尤其在基层医院。肿瘤内科的疼痛管理第33页病人经济问题1.因为药品价格较高，病人往往需要长久使用，没有医保或就是有医保病人经济负担依然较重。2.对于没有报销起源病人，长久治疗疼痛药品根本负担不起。3.这也是造成国内当前为止杜冷丁依然有很多医院仍在使用主要问题。4.肿瘤病人疼痛问题作为一个人道问题处理方法可能是提供无偿药品。肿瘤内科的疼痛管理第34页药品品种缺乏1.止痛药品在国内和发达国家相比依然稀少。2.基层医院更为显著，是杜冷丁仍在使用一个主要原因。3.同一品种规格不全，甚至造成不能正确给病人合理剂量。4.不一样医院差异显著。5.新药开发较少。肿瘤内科的疼痛管理第35页病人教育1.病人对于晚期癌症疼痛存在误区，对于合理使用麻醉药品存在一定恐惧感。2.因为不愿意使用，使得相当大一部分病人没有得到合理治疗。3.对于晚期癌症病人心理疏导国内几近空白。4.大部分肿瘤科医生缺乏使用抗焦虑药品经验。肿瘤内科的疼痛管理第36页医务人员对肿瘤病人疼痛不作为1.对肿瘤治疗中往往忽略了肿瘤疼痛治疗。2.就是对肿瘤疼痛给予关注，但也不能给病人以理规范化疼痛治疗。3.临床上仍有给予病人短效制剂，针剂或杜冷丁现象。4.因为三阶梯止痛方案影响，不能较早及时给病人强阿片类药品处理。5.对于阿片类药品副作用处理不及时，不重视。6.对于难治性疼痛缺乏有效方法。7.过分依赖非甾体抗炎类药品。8.对于疼痛评介标准不是很清楚。肿瘤内科的疼痛管理第37页药品企业对疼痛产品开发不足当前国内强阿片类药品品种和剂型均较少相关药品研发较为落后。没有对应管理机构保障。对于现有品种没有按照特殊药品处理。相关药品价格较高。肿瘤内科的疼痛管理第38页缺乏对应符合国情疼痛治疗指南1.当前虽有NCCN疼痛指南，不过对于国情仍有一定差异。2.当前国内大部分医院没有专业疼痛处理队伍或疼痛门诊。3.没有治疗疼痛小组，其组员包含肿瘤内科医师，外科医师，麻醉科医师，介入科医师，放射科医师，护士，心理医师。4.国内晚期癌症病人以门诊处理为主，缺乏小区医生处理。5.对于初诊病人滴定多数医院没有开展。6.没有一个统一合理疼痛处理规范。7.比如当前已经将晚期癌症病人疼痛处理中定义为只要有疼痛就能够用阿片类药品，但在国内仍不是共识。8.受三阶梯疼痛治疗方案影响较大，不过政府部门依然作为一个主要标准，和当前临床实践不符。9.怎样制订一个简单易行符合国情疼痛治疗指南是当前一个主要问题。肿瘤内科的疼痛管理第39页国内当前临床上疼痛处理流程晚期癌症疼痛病人首次使用治疗疼痛药品即往使用过阿片类或复方制剂疼痛评分以及疼痛原因评定疼痛评分以及做剂量换算4分以下5-10分奥施康定，美施康定或芬太尼贴剂弱阿片类或复方制剂奥施康定，美施康定或芬太尼贴剂一个处方周期后评定5-10分肿瘤内科的疼痛管理第40页对于难治性疼痛缺乏共识当前疼痛药品治疗大约能够控制80-90%晚期癌症疼痛病人，其它病人不能经过药品得到很好疼痛控制，这部分病人疼痛需要使用抗焦虑药品，介入治疗，包含神经阻滞，综合治疗。因为这些技术不在肿瘤内科范围，所以这部分病人合理治疗得不到保障。对于当前这部分病人我们当前处理经验采取皮下泵吗啡方法取得很好效果。肿瘤内科的疼痛管理第41页谢谢！肿瘤内科的疼痛管理第42页