末期病人疼痛處置概論ppt課件

1、末期病人疼痛處置概論末期病人疼痛處置概論Woei-Yau Kao, MD, PhDTri-Service General HospitalNational Defense Medical CenterOutlinenGeneral guidelines (Pharmacology, titration)nTransdermal fentanyl patchnOpioid tolerance, Hyperanalgesia, Withdrawal symptomsnOpioid rotationnAddition of a second opioidnCombination of opioid

2、agonists and antagonistsnRenal/hepatic failure, old mannSummary 疼痛用藥原則n經(jīng)口服藥n按時(shí)用藥n階梯步驟n個(gè)人化原則n參與輔助用藥n留意細(xì)節(jié)n最大效果與最小副作用癌癥疼痛的評(píng)估-1n疼痛是主觀感覺n所以止痛，要以顧客滿意度為最重要考量癌癥疼痛的評(píng)估-2n普通運(yùn)用VAS (visual analog score) 方式，讓病人挑選一個(gè)圖案代表此時(shí)疼痛情形，做為評(píng)估治療的依據(jù)。1-34-67-10癌癥疼痛的評(píng)估-3n癌癥病人的疼痛，絕大部分與癌癥本身有關(guān)，可以用止痛藥緩解。n但是病人也有能夠出現(xiàn)別的疾病，此時(shí)一定要先仔細(xì)評(píng)估，才不會(huì)

3、遺漏：n腸穿孔、急性闌尾炎、心肌堵塞n病理性骨折n也就是要先排除急癥的能夠性Mantyh PW et al. Nature reviews cancer 2019Adapted from WHO. Cancer Pain Relief, with a Guide to Opioid Availability. 2019.Ultracet(7-10)(4-6)(1-3)Choice of Opioid AnalgesicRecommendation from AHCPR Cancer Pain Guidelines Panel:“The simplest dosage schedules and

4、least invasive pain management modalities should be used first(Panel Consensus)重度疼痛快速生效之短效嗎啡，運(yùn)用腸胃蠕動(dòng)劑止吐藥合併運(yùn)用止痛藥物敎育病人心思支持(1/6)Around the clock非鴉片類止痛用藥nNSAID or Cox-2 n具抗發(fā)炎效果，通常用於骨轉(zhuǎn)移和軟組織疼痛。n選擇半衰其較短的藥物，調(diào)整較富彈性。n通常止痛效果越強(qiáng)者，副作用較多。n普通以建議量之最小量開始運(yùn)用，留意其極限效應(yīng)Ceilings effect。n可與Opioid併用。Classical type of opioid re

5、ceptor: m, k, dActions of OpioidsReceptor Prototype stimulator Effect Mu1 Morphine Supraspinal and spinal analgesia Feelings of well-being Mu2 Respiratory depression GI motility、Urinary retention Miosis、Bradycardia Physical dependence Kappa Dynorphin Spinal analgesia、Dysphoria Psychotomimetic effect

6、s Slight miosis and respiratory depression Delta Enkephalin Spinal analgesia Respiratory depression May act synergistically with mu receptor Gourlay GK Support Care Cancer 2019;13:153-9Opioid binding affinities常見鴉片類止痛劑的副作用n鎮(zhèn)靜、呼吸抑制、噁心/嘔吐、便秘*、皮膚癢、口乾*、小便困難/滯留、睡眠異常、幻覺、耐藥性*、依賴性*、情緒改變*、肌肉陣攣*n * 經(jīng)長(zhǎng)期運(yùn)用仍能夠持續(xù)

7、弱效鴉片類止痛藥nCodeinenTramadolnUltracetnProxyphene (Depain X) n防止長(zhǎng)期運(yùn)用 MeperidineTramadoln中樞及周邊的非成癮性止痛劑n低度結(jié)合鴉片類受體，活化脊髓內(nèi)鴉片類受體n抑制 Serotonin 及 Noradrenaline 的再吸收。n口服劑量 Ceiling effect (+)n起始：100 mg/q12h 或 50 mg /q6hn普通：200 mg/q12h 或 100 mg/q6hn衛(wèi)生署合格通過為非成癮性控制用藥之鴉片類止痛藥。n副作用：噁心、嘔吐、暈眩。ULTRACET Body System (% of P

8、atients)Preferred Term N = 142 Gastrointestinal SystemConstipation6Diarrhea3Nausea3Dry Mouth2 Psychiatric DisordersSomnolence6Anorexia3Insomnia2 Central & Peripheral Nervous SystemDizziness3 Skin & AppendagesSweating Increased4Pruritus2 Reproductive Disorders, MaleProstatic Disorder2Ortho-Mc

9、Neil Pharmaceutical. ULTRACETPrescribing Information. August 2019.Treatment-Emergent Adverse Events, 2% of PatientsMeperidine (demerol、pethidine)n針劑脂溶性高，起始作用時(shí)間快，常用於外科手術(shù)後止痛。n作用期短3-4小時(shí)，口服效果差，重複運(yùn)用亦發(fā)生毒性代謝物normeperidine)累積，導(dǎo)致中樞神經(jīng)中毒顫抖、混亂、癲癇發(fā)作 。n不易監(jiān)測(cè)過量作用，無有效中和劑。n不適用於慢性疼痛。Incidence of weak opioids adverse e

10、vents in the management of cancer painnA double-blind comparative trial.nWith the objective of comparing incidence of adverse events of the opioids codeine, hydrocodone, and tramadol in the relief of cancer pain nOf the 177 patients who participated, 62 patients received hydrocodone, 59 patients rec

11、eived codeine, and 56 patients received tramadol. nNo significant statistical difference in the analgesic efficacy of the three opioids was found (p: 0.69; chi(2): 0.73). Use of tramadol produced higher rates of adverse events than codeine and hydrocodone: vomiting, dizziness, loss of appetite, and

12、weakness (p 0.05). Rodriguez et al., J Palliat Med. 2019 Feb;10(1):56-60 nIV, SC, rectal route, oral:nShort acting vs long actingnDose conversion: nPRN dosenComplications強(qiáng)效鴉片類止痛藥n作用與副作用均類似n單純的 agonist opioids 無極限藥量限制No Ceiling Effect，藥量增大則止痛效果持續(xù)加強(qiáng)，但副作用亦隨之添加強(qiáng)效鴉片類止痛藥nMorphine nFentanyl transdermal pat

13、chnTemgesic (Buprenorphine hydrochloride) SLnButaro (butorphanol tartrate) nasal sprayMorphine Pharmacology & Molecular biologynThe multiple m opoid receptors may help explain the range of responses seen clinically among patients for the various opioid drugs.Receptor Prototype stimulator Effect

14、Mu1 Morphine Supraspinal and spinal analgesia Feelings of well-being Mu2 Respiratory depression GI motility、Urinary retention Miosis、Bradycardia Physical dependence Kappa Dynorphin Spinal analgesia、Dysphoria Psychotomimetic effects Slight miosis and respiratory depression Delta Enkephalin Spinal ana

15、lgesia Respiratory depression May act synergistically with mu receptor Pasternak GW. J Pain Symptom Management 2019嗎啡的藥理作用 口服短效嗎啡 口服長(zhǎng)效嗎啡 皮下注射嗎啡 Onset 15-60 min 60-90 min 15-30 min Peak 30-60 min 1-4 hours 50-90 min Duration 2-7 hours 6-12 hours 2-7 hours 口服嗎啡之劑量調(diào)整n初次運(yùn)用：短效嗎啡 5mg/q4h 規(guī)則運(yùn)用。n夜間可將兩個(gè)固定劑量合

16、併服用。n以每日總量 1/6 為p.r.n.劑量，頻次可設(shè)為 1 至 4 小時(shí)一次。n隔日以前一天運(yùn)用之固定量加上額外運(yùn)用量為當(dāng)日總量，分六次服用，p.r.n.與夜間劑量也隨之調(diào)整。n當(dāng)疼痛控制穩(wěn)定後，將每日短效服用嗎啡總量，分成2 至 3 份Q8 - 12H的長(zhǎng)效型嗎啡，但仍以短效嗎啡為 p.r.n. 用藥。Donnelly S et al. Support Care Cancer 2019Dose escalationnIncrease the initial calculated dose by 20% if the pain is poorly controllednConsider

17、increasing the regular dose if the patients require more than 4 rescue doses in 24 hrsnReview and adjust the (regular, prn) dose q24h until the pain is controlledOpioid Dose Titration for Severe Cancer PainHagen 2019 Klepstad 2000Mercadante 2019Morphine 10-20 mgIR oral morphineMorphine 2 mg q2minIV

18、over 15 minstarting with 10 mgx6 10 cases 40 cases 45 casesDouble the doseA fixed schedule withq2min until initial signsq30min until analgesia33-50% each dayof significant analgesia (10,15, 20,30,45,60)& immediately convertedto oral morphine89 min (4-215 min)2.3 days (1-6 D)9.7 min (7.4-12.1 min

19、)97 mg/D (60-180mg)8.5 mg (6.5-10.5 mg)Davis MP et al., J Palliat Med2019;7(3):462-8 Opioid Dose Titration for Severe Cancer PainnRegardless of the regimen, the majority of patients had their pain relieved within 24 hrs (level III-D)nThe onset to analgesia is fastest for parenteral dosing schedules

20、(level III-A)nNo difference between SR and IR oral opiates for acute pain (level III-A)Davis MP et al., J Palliat Med2019;7(3):462-8Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trialnStarting dose 60 mg/day (oral)nA

21、 fixed titration schedule (60-90-120-180-270-360 mg)nMorfin (IR) vs Kapanol (SR)nMean time needed for titration: nIR 2.1d (1.4-2.7) vs SR 1.7 d (1.1-2.3)nA simplified titration using SR morphine is equally as IR morphineKlepstad P et al., Pain 2019;101:193-8Recognition, diagnosis & treatment of

22、breakthrough pain (BTP)nSubtypes: incident, idiopathic, & end-of-dose failure. nAlso categorized as somatic, visceral, neuropathic, or mixed. nShort-acting opioid analgesics are the primary treatment. nThe dose and/or dosing frequency of the ATC analgesic should be adjusted for patients with end

23、-of-dose BTP. nShort-acting oral opioids are useful when given preemptively in patients with predictable incident BTP, while rapid-onset transmucosal lipophilic opioids are most effective for patients with unpredictable incident or idiopathic BTP. McCarberg BH .Pain Med. 2019;8 Suppl 1:S8-13.Payne R

24、 2019;8 Suppl 1:S3-7. Inadequate pain management Difficult pain problem Mixed patternMercadante S et al. Cancer 2019Differentiation of episodic painMercadante S et al. Cancer 2019Algorithm for treatment of breakthrough painMercadante S et al. Cancer 2019Algorithm for treatment of neuropathic breakth

25、rough painMercadante S et al. Cancer 2019Rescue dosenIndividualized: Opioid-nave vs opioid-takingnIV, SC (onset delay 30 min) or short-acting oral formnDosing & dosing intervalnOral: 5%-10% of daily oral opioid dose as needed q2-3 hrs (Portenoy RK et al., Pain 1990); 10-20% of daily oral opioid

26、dose as needed q1hr (NCCN guideline)nIV/SC: 10-20% of daily IV opioid dose as needed q15 min; 50%-200% of daily IV opioid dose as needed q15 min (NCCN guideline)Nelson KA et al., J Pain Symptom Manage 2019Breakthrough DosingDonnelly S et al. Support Care Cancer 201950% of hourly doseDose conversionn

27、IV : Oral = 1:3 for low dosesn = 1:2 for high dosesHanks GW et al. BMJ 2019Mercadante S et al. Cancer 2019Donnelly S et al. Support Care Cancer 2019如何換算如何換算Durogesic 的劑量的劑量?nDurogesic Oral morphinen 25(g) 60 (30 90) mgn 50 120 (90 150)n 75 180 (150 210)n 100 240 (210 240)n 125 300 (270 330) For ever

28、y additional 60 mg, increase Durogesic 25 mcg/hrsMuijers RBR et al, Drugs 2019;61:2289-2307Fentanyl TTS (Durogesic)n強(qiáng)效鴉片類止痛劑n作用：n活化(supraspinal)與(intraspinal)接受器。n抑制 spinothalamic tract 損害性訊息的傳導(dǎo)。n代謝n主要經(jīng)肝臟代謝 (hepatic dealkylation)n75% 經(jīng)尿液排泄n老年人、腎臟去除率較差者謹(jǐn)慎運(yùn)用Durogesic 貼片12 HFentanyl transdermal patchn以

29、簡(jiǎn)單、非侵入性的方式提供穩(wěn)定的Fentanyl 血中濃度，發(fā)揮止痛效果。nFentanyl transdermal patch：25、50 ug/hr n每72小時(shí)換一次，少數(shù)人需48小時(shí)換一次。Fentanyl TTS v.s. 口服Morphinen同樣提供良好的疼痛控制效果n便秘、噁心、嘔吐、皮膚癢比率較少發(fā)生n白天嗜睡等常困擾病患的鴉片類副作用較低n呼吸抑制：比率和嗎啡一樣低。n過敏作用：和黏貼劑有關(guān)，可以用 antihistamine 處理。Withdrawal symptoms during therapy with transdermal fentanylnDespite goo

30、d pain control, severe abdominal withdrawal symptoms (diarrhea, headache, abdominal cramps, nausea, sweating, freezing, shivering and restless)nFentanyl dosages toward the upper end of conversion rangenResolved after converting back to usual dose of morphineZen M et al. J Pain Symptom Manage 1994Hig

31、gs CMB. J Pain Symptom Manage 2019Donnelly S et al. Support Care Cancer 2019Diffenences in analgesic or adverse effect responses among opioids nMechanisms:nReceptor activitynThe asymmetry in cross-tolerance among opioidsnDifferent opioid efficaciesnAccumulation of toxic metabolitesMercadante S. Canc

32、er 2019;86:1856-66Opioid therapy for chronic pain Ballantyne JC et al.,NEJM 2019;349:1943-3nDaily doses above 180 mg of morphine or a morphine equivalent have not been validated in clinical trials involving patients with chronic pain and might be considered excessivenReference:nThe Journal of Pain:

33、5(2): 119-132, 2019IntroductionnTTS-fentanyl is a long acting, controlled release opioid preparation. Compared to morphine, TTS-fentanyl has less severity and incidence of constipation.nSome studies interested in using TTS-fentanyl in select cancer patients experiencing severe intolerable or chronic

34、 persistent pain, avoiding step I and II of WHO ladder. Results (1)286 (15.6%)1239 (67.8%)321 (17.6%)1828 (100%)Results (2)Efficacy of Durogesic from WHO 3 Ladder無論病患之前運(yùn)用哪種止痛藥品，運(yùn)用了無論病患之前運(yùn)用哪種止痛藥品，運(yùn)用了Durogesic之後，病之後，病患的疼痛有獲得顯著的改善?；嫉奶弁从蝎@得顯著的改善。Results (5)QoL by Cancer site無論病患的癌癥部位為何，運(yùn)用了無論病患的癌癥部位為何，運(yùn)用了

35、Durogesic之後，病患的生之後，病患的生活品質(zhì)都有獲得顯著的改善。活品質(zhì)都有獲得顯著的改善。Results (6)Satisfaction of Durogesic from WHO 3 Ladder無論之前運(yùn)用的止痛藥為何，運(yùn)用了無論之前運(yùn)用的止痛藥為何，運(yùn)用了Durogesic之後，病患的之後，病患的對(duì)止痛藥的滿意度有顯著的提升。對(duì)止痛藥的滿意度有顯著的提升。Transdermal fentanyl versus sustained-released oral morphine in cancer pain: prevalence, efficacy and quality of l

36、ifenRandomized to receive SR morphine or transdermal fentanyl for 15 days, followed by a further 15 days treatment with the other medication. (N=202)nFentanyl: less constipation, less daytime drowsinessnFentany patch more preferred (p=0.037)Ahmedzai S et al. J pain symp manag 2019IssuesnOpioid toler

37、ancenOpioid additionnOpioid withdrawal symptomsnOpioid hyperanalgisianOpioid intoxicationOpioid-induced Hyperalgesia - an emerging iatrogenic syndromenExacerbating a preexisting painnDiffuse, less defined in quality, beyond the distribution of preexisting painnQuantitative sensory testing: changes i

38、n pain, threshold, tolerability, distribution patternnWorsened pain following an increase in opioid dosesMercadante S et al. J pain symptom manage 2019;26(2):769-75Approach to a patient on opioid regimen with increased painnIncreased nociceptive activities (disease progression)nPsychological process

39、nPharmacologic tolerancenOpioid-induced hyperalgisianPhysical dependencenSymptoms of withdrawalnAddictionOpioid rotationIndication:development of tolerance, appearance of intractable side effectsSwitching the route of administrationSwitching the opioid: Mercadante S. Cancer 2019;86:1856-66Opioid rot

40、ationThe second opioid can be started at half the dose equivalent of the first, because the patients tolerance to the second will be lower.Ballantyne JC et al., NEJM 2019;349:1943Opioid switch in palliative care, opioid choice by clinical need and opioid availabilityMuller-Busch HC et al. Eur J Pain

41、 2019;571-9Stouz ND et al. J pain symptom manag 2019:10:378-384Opioid rotation for toxicity reduction in terminal cancer patientsAddition of second opioid may improve opioid response in cancer pain Mercacande S et al. Support Care Cancer 2019Addition of second opioid may improve opioid response in c

42、ancer painMercacande S et al. Support Care Cancer 2019Walsh D. Support Care Cancer 2019Opioids in renal failure and dialysis patientsnMorphine and codeine: avioidednHydromorphine or oxycodone: with caution and close monitoringnMethadone and fentanyl/sufentanil: safe to useDean M. J Pain Symptom Manage 2019;28(5):497-504Murphy EJ. Anaesth Intensive Care 2019;33:311-22Acute pain management pharmacology for the patients with concurrent hepat