癌症患者的疼痛控制 謝瑞坤 醫師 血液暨腫瘤科 馬偕紀念醫院

癌症疼痛問卷 2001 您是否有過疼痛的困擾 ? 53.5% 您覺得當時疼痛的程度 輕微 29.3% 中度 35.6% 最痛 35.2% 您是否有過疼痛的困擾 ? 53.5% 您覺得當時疼痛的程度 輕微 29.3% 中度 35.6% 最痛 35.2% 您現在有無服用控制疼痛的止痛藥物 ? 58% 服用止痛藥物後, 您對疼痛問題的改善情況滿意嗎 ? 64.2% very to Satisfied

WHO及許多醫學會皆指出癌病疼痛可由一些簡單的治療方式在90%的患者得到有效的處置

癌病疼痛控制的障礙 醫護人員 疼痛處置的知識不足 疼痛評估不適當 對藥品管制法令的過分顧慮 害怕導致患者成癮 過分顧慮止痛藥物的副作用 顧慮患者會對藥物產生抗藥性 tolerant to analgesics.

癌病疼痛控制的障礙 患者 猶豫告知疼痛 顧慮會因而使醫師不能專心於其癌病 恐懼疼痛可能是癌病惡化的徴象 怕未能表現為一“好”病患 猶豫而未服用止痛藥物 害怕成癮或被認為是一成癮者 擔心藥物的副作用 擔心藥越用越無效

治療癌症的疼痛之三大原則 疼痛評估 選擇適當的治療方法 持續照顧 聯合國世界衛生組織

疼痛評估 疼痛評估的目的是為了詳盡了解患者病況,疼痛性質與部位及患者所受的影響 評估的內容: 詳細的病史 理學檢查 心理社會評估 其他輔助性檢查 Failure to assess pain is a critical factor leading to undertreatment. Pain assessment should be comprehensive, particularly at the initial stage. The goal of initial assessment is to characterize pain pathophysiology, and to evaluate pain intensity and its impact on the patient's life. Essential components of initial assessment are: Detailed history Physical examination Psychosocial assessment Diagnostic evaluation In addition to the physical and functional aspects, psychosocial and spiritual dimensions should also be assessed. This should include assessment of anxiety and depression, and the patient’s beliefs about pain. Reference: Otis-Green S, Sherman R, Perez M, et al. An integrated psychosocial-spiritual model for cancer pain management. Cancer Pract 2002;10 Suppl 1:S58-65.

評估的基本原則 相信病人的疼痛抱怨 仔細詢問癌症及疼痛相關病史 評估心理狀態、可請精神科協助 進行理學、神經學檢查 開立診斷方式：如CT，bone scan，MRI 開始治療疼痛以便利適當檢驗 重新評估治療的反應 再設計、討論進一步治療方式

患者的自我評估報告 Self-Report 疼痛評估的主幹 可幫助患者描述: 疼痛 PAIN 部位 LOCATION 嚴重程度 INTENSITY OR SEVERITY 加強或減輕的因素 AGGRAVATING AND RELIEVING FACTORS 疼痛的認知及反應 COGNITIVE RESPONSE TO PAIN 疼痛控制的目標 GOALS FOR PAIN CONTROL

常用疼痛量表 疼痛量表(VAS, Visual Analog Scale)：在一條 10 公分長度的水平直線，以最左處作為零點，代表完全無疼痛；直線的最右端為所能想像中最嚴重的疼痛，患者依其對所感疼痛的程度在直線上標示。 這是一個以患者本身疼痛經驗來將疼痛的嚴重程度作一量化的表達，類似的疼痛在不同患者的經驗感覺可能在量表上有全然不同的表達。

持續疼痛評估 Pain Assessment 評估過程包括醫護人員與患者 而且 開始治療後要定期評估 有新的疼痛要再做評估 在給藥物或非藥物治療疼痛後在適當的觀察時間後即予評估

癌症疼痛 了解疼痛之病理生理學機制,有助於醫師提供更有效的治療方式 對某些病患而言,可能同時合併不同類別的疼痛 癌症疼痛型態 體感性疼痛(Somatic pain) 內臟性疼痛(Visceral pain) 神經病變性疼痛(Neuropathic pain) Effective management of cancer pain cannot be possible without knowing its pathophysiology. Importantly, it should be noted that patients may experience a combination of pain types. There are 3 types of pain: somatic, visceral, and neuropathic pain.

體感性疼痛 體表,肌肉和骨骼受損所引發,如骨轉移 這類疼痛病患可以明確指出痛處,其性質常為刀刺痛(stabbing), 銳痛(sharp),博動性疼痛(throbbing)等。 此類疼痛對止痛藥物的反應佳 Somatic pain results from damages to cutaneous and musculoskeletal tissues. Typical example is the pain caused by bone metastasis. Somatic pain is well-localized, and is described as sharp, stabbing, or throbbing in nature. Of the various types of pain, somatic pain usually responds best to analgesics.

內臟性疼痛 原因包括臟器受損,中空器官阻塞, 平滑肌痙攣等 定位困難,通常有悶痛(dull),絞痛(cramping)等,甚至會以不明的體表疼痛(referred pain)出現 患者亦可能出現自主神經障礙的症狀,如噁心,嘔吐,低血壓,心博過緩,冒汗等 大多數這類疼痛的患者需要接受鴉片類藥物止痛治療 Visceral pain is commonly caused by organ damage, hollow organ obstruction, or smooth muscle spasm. It is poorly localized and the patient may describe the pain as dull or cramping type of discomfort that may be referred to sites remote from the primary injury. The hallmark of visceral pain is the emergence of accompanying autonomic symptoms such as nausea/vomiting, hypotension, bradycardia, and sweating. Most patients with visceral pain will respond to opioid therapy.

神經病變性疼痛 乃神經組織受損所致,常會引起劇烈的疼痛 患者會出現dysesthesias(不悅異常感),為從未經歷過的不愉快感覺,屬於感覺異常的一種性質多變化如灼痛(burning),刺痛(tingling),電擊痛(shock-like) 其他尚包括觸摸痛(allodynia),痛覺過度(hyperalgesia)和遲鈍(hypalgesia) 這類型的疼痛常需要合併輔助劑治療,如抗憂鬱劑或抗痙攣劑 Neuropathic pain results from damage to neural structures and can have a great variety of presentations. The affected patient often complains of dysesthesias (abnormal pain complaints) that are new to the patient. The pain may be described as burning, tingling, or shock-like. Other findings may include allodynia (pain on light touch), hyperalgesia, and hypalgesia (altered sensitivity to noxious stimuli). Neuropathic pain is relatively resistant to opioids and therefore usually requires the addition of adjuvants such as antidepressants and anticonvulsants.

偶發痛 Incident Pain 指當身體移動時會出現的疼痛 治療方式通常和突發性疼痛相同 其他的治療方式如下 找出最理想的突發性疼痛止痛藥物 在移動身體前,先服用突發疼痛型藥物作預期性疼痛的預防 適當地使用非鴉片類止痛劑和輔助劑 考慮放射型治療,神經阻斷和手術治療 Incident pain is the pain associated with body movement and is usually treated in the same way as breakthrough pain. The measures below may also help: Optimize background analgesia with long-acting opioids. Treat exercise-related pain with anticipatory analgesia (take a breakthrough dose 30 minutes before exercise). Use non-opioids and adjuvants appropriately. Consider other modalities such as radiotherapy, nerve blocks, and stabilizing surgery.

特殊疼痛病況及併發症的藥物治療 病況 用藥原則 骨折 NSAIDs 可考慮手術 脊髓壓迫症候群 Dexamethasone 10-100 mg IV 緊急放射線治療 腸道阻塞 評估手術，opioids 控制疼痛 上腔靜脈症候群 Dexamethasone 10 mg IV 顱內高壓 Dexamethasone 10 mg IV, 懷疑 herniation 可用100 mg IV. Mannitol 20% 不宜使用 opioids 頑固型神經病變性疼痛，如 post-herpetic Phenytoin 15mg/kg IV load Lidocaine 5mg/kg IV infusion 發炎性反應疼痛，如骨轉移及肋膜炎疼痛

藥物治療原則 遵循藥物治療的基本原則，可控制70-90%的癌症疼痛,例如世界衛生組織基本原則如下： l 口服給藥 “by mouth” l          按時給藥 ”by the clock” l          依階段給藥 “by the ladder” l          因人而異給藥 “for the individual” l          注意細節 “attention to detail”

WHO 建議的止痛三階段治療準則 Co-analgesics Strong Opioids ± Non-Opioids Ex: Fentanyl-TTS, Morphine, Methadone Severe Weak Opioids ± Non-Opioids Ex:. Codeine, Tramadol, Tilidin/Naloxon Moderate Mild pain can be treated with a Step 1 analgesic such as acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID). If pain persists or worsens, a change to a Step 2 or 3 analgesic is indicated. Most patients with cancer pain will require a Step 2 or 3 analgesic. Frequently, Step 1 is skipped in patients presenting initially with moderate-to-severe pain. At each step, an adjuvant drug or modality such as radiotherapy can be considered in selected patients. 從世界衛生組織(WHO)的用藥建議中，當一個癌症病人為〝輕度疼痛〞時，使用非鴉片止痛藥止痛，而當一個癌症病人為〝中重度疼痛〞時， 此時不需先用非鴉片止痛藥，則應馬上使用 鴉片止痛藥止痛。 Non-Opioids Ex: ASA, Ibuprofen, Diclofenac, Cox 2-inhibitors, Paracetamol, Metamizol, Flupirtin Mild

癌症疼痛藥物止痛療程應顧及： 疼痛之長期、穩定控制:以按時使用（by the clock）的長效性鴉片類藥物達成（around-the-clock medication）。 突發性疼痛（breakthrough pain）之緩解:以按需要服用的短效性鴉片類 偶發性疼痛（incident pain）

Acetaminophen and NSAIDs 此類藥品僅限於緩解輕度體感性疼痛 NSAIDs與鴉片類藥物合併使用,並未顯著減少癌症疼痛患者的鴉片類藥物用量 老年患者(>60y/o),患有慢性疾病如腎臟病,肝臟病或心衰竭的患者在投與這類藥物時,要小心謹慎副作用的發生 對於吸煙者,有消化性潰瘍病史以及接受口服類固醇或抗凝血劑治療的患者也要小心使用 這類藥物有天花板效應(Ceiling effect)(即在使用至一相當劑量後,再增加劑量也不會有更好止痛效果) The effectiveness of acetaminophen and NSAIDs is usually limited to relief of mild somatic pain. A recent meta-analysis suggests that NSAIDs generally do not significantly spare opioid doses.[1] Patients taking acetaminophen or NSAIDs, including elderly patients (>60y/o) and patients with chronic disease (renal or hepatic disease or cardiac failure), should be followed carefully for side effects.[2] These agents should also be used cautiously in smokers, in patients with a peptic ulcer history and in those receiving oral corticosteroid or anticoagulant therapy.[3] They are also subject to a ceiling effect. References: Alkhenizan A, Librach L, Beyene J. The role of NSAIDs as adjuvant and opioid sparing analgesics in the management of cancer pain: a meta-analysis. Research in Palliative Care: 2nd Congress of the Research Network of the EAPC, 23-25 May 2002, Lyon, France. A-84. Committee on Safety of Medicines. NSAIDs and Renal Adverse Reaction. In Current Problems (32) October 1991. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994;343:769-72.

Acetaminophen and NSAIDs 建議口服,在發生噁心嘔吐時,可採用栓劑投與 肌肉注射(IM)基於藥物吸收的不可靠即施打時的疼痛問題,一般不建議使用 NSAIDs(Acetaminophen除外)對血小板功能會產生抑制作用,因此不適用於凝血障礙及出血傾向的患者 若產生胃腸道副作用的風險較高時,建議可於治療同時,給予misoprostol一天2~3次每次200mcg作為預防.若患者已出現胃腸道副作用,但仍需持續NSAIDs治療時,則可給予每天omeprazole 20 mg 一次 The oral route of administration is preferred. Suppositories can be used during intervals of nausea and vomiting. Use IV injection if the parenteral route is indicated, because IM injection is more painful and less reliable in terms of absorption. NSAIDs (except acetaminophen) are contraindicated in patients with coagulopathy or bleeding tendency. Patients taking a NSAID who are at risk of GI side effects should be given misoprostol 200mcg 2-3 times daily. Patients who have developed GI side effects but require continuous NSAID therapy should be given omeprazole 20mg daily.

鴉片類藥物 在癌症疼痛的控制上,鴉片類藥物為主要且最有效的藥物。 對鴉片類藥物的誤解使得鴉片類藥物優異的止痛效果無法發揮 Opioids constitute the major class of analgesics used in cancer pain management. Unfortunately, the misunderstanding about opioids has resulted in the underutilization of these effective medications and undertreatment of many patients. Reference Whitcomb LA, Kirsh KL, Passik SD. Substance abuse issues in cancer pain. Curr Pain Headache Rep 2002;6:183-90.

耐藥性 (Tolerance) 長期鴉片類藥物治療下的生理變化 劑量的增加通常反映癌症病況的惡化 因耐藥性而需要接受鴉片類藥物劑量增加的病例並不常見 長期治療下，不少患者在不良反應的表現上（如鎮靜、呼吸抑制等），卻會因「副作用耐藥性」的出現而受益

生理依賴性 長期鴉片類藥物治療下的生理變化，若治療突然中止／劑量驟降，患者會出現戒斷症候群（withdrawal syndrome） 鴉片類藥物的使用正確，生理依賴性並不會構成鴉片類藥物治療的阻礙 戒斷症候群可藉著以下措施加以預防： 避免使用鴉片類藥物受體之 partial agonists 或 mixed agonist-antagonists 非必要時（例如顯著之呼吸抑制），避免使用鴉片類藥物 拮抗劑(antagonist) 謹慎進行鴉片類藥物劑量之減量過程。

弱效鴉片藥物 Weak Opioids 弱效鴉片藥物包括codeine, tramadol, and dextropropoxyphene 。通常用於輕度到中度的疼痛。 沒有證據顯示一弱效鴉片藥物效果優於另一者。 和dextropropoxyphene比較, codeine在耐受性方面較好且較常被建議使用。 Tramadol是一個對monoaminergic system會產生影響的類鴉片藥物,但在臨床劑量範圍內,其止痛效果和劑量調整空間有限。 若任一弱效鴉片藥物,無論單獨治療或與非鴉片藥物合併投與,無法達到足夠的疼痛控制時,應直接進行第三階段的疼痛治療 Weak opioids include codeine, tramadol, and dextropropoxyphene. They are used in patients with mild to moderate pain (WHO ladder step 2). At therapeutic dose range there is no evidence that one weak opioid is more effective than another. Compared to dextropropoxyphene, codeine is better tolerated and thus more frequently used. Tramadol is an opioid with additional effects on the monoaminergic system[1], but its use is limited because there is little room for titration– it can cause convulsions at doses just above the normal therapeutic dose range[1,2]. Hence tramadol does not appear to be superior to other weak opioids. If the effect of optimal treatment with any weak opioid is not adequate when used alone or in combination with non-opioids, do not try another weak opioid. Move to step 3 of the WHO analgesic ladder. References: Tramadol—a new analgesic. Drug Ther Bull 1994;32:85-7. Committee on Safety of Medicines. Tramadol (Zydol)- psychiatric reactions in Current Problems (21) February 1995.

鴉片類藥物給藥原則 對大部分的癌症疼痛患者而言, 穩定而有效的疼痛控制有賴於定時投與日夜連續型(around-the-clock)鴉片類藥物和需要時投與突發疼痛型鴉片類藥物。 每次突發疼痛型鴉片類藥物的劑量為日夜連續型鴉片類藥物全日劑量的1/6( or 5~15%),且使用次數以一天內不超過3次為原則。 雖然嗎啡可同時作為日夜連續型和突發疼痛型止痛用藥,但為了促進患者對長期疼痛治療的醫屬順從性,日夜連續型止痛用藥仍以長效型嗎啡或是Durogesic為最適合。 These are opioids used in patients with moderate to severe pain (WHO ladder step 3). Morphine is the opioid of choice for oral use with well-established efficacy and safety. Morphine is available as normal release and controlled release preparations, commonly known as “morphine” and “MS Contin”, respectively. Transdermal fentanyl (Durogesic) has been shown to be as effective as morphine in cancer pain relief.[1,2] It is in form of a patch delivery system that is replaced every 72 hours (48 hours in a minor group of patients), thus avoiding the inconvenience associated with the around-the-clock administration of morphine. There is also growing evidence that transdermal fentanyl causes less constipation than morphine.[3,4] However, because of the delayed onset of action, transdermal fentanyl is not recommended for treatment of acute pain or poorly controlled pain. Meperidine (Demerol) is not recommended for the long-term treatment of cancer pain due to its short duration of action (2.5-3.5 hours) and accumulation of its neurotoxic metabolite, normeperidine. References: Ahmedzai S, Brooks D. Transdermal Fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy and quality of life. The TTS-Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997;13:254-61. Payne R, Mathias SD, Pasta DJ, et al. Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol 1998;16:1588-93. Radbruch L, Sabatowski R, Loick G, et al. Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine. Palliat Med 2000;14:111-9. Donner B, Zenz M, Strumpf M, Raber M. Long-term treatment of cancer pain with transdermal fentanyl. J Pain Symptom Manage 1998;15:168-75.

AHCPR癌症疼痛共識 癌症疼痛處理應以”最無侵入性”及”最簡單給藥時間”的治療方式優先使用 。 口服或是穿皮貼片劑型為優先選擇方式。 注射劑型只有在簡單,無侵入性和最小傷害性的方法都無法投與時,才可使用。 針劑嗎啡的生體可用率約為口服劑型的2~3倍,因此在進行口服劑和針劑轉換時,需作出劑量上相對的調整。 According to AHCPR Cancer pain guidelines panel consensus, the simplest dosage schedules and least invasive routes should be used first. Therefore, oral administration and transdermal route are preferred because of its convenience and safety. Parenteral administration should be used only when these simpler, less invasive, and less demanding methods are not feasible. The bioavailability of parenterally given opioids including morphine is 2-3 times higher than that of the oral route. The dose therefore needs to be halved or decreased by a third when converting from the oral to the subcutaneous and intravenous routes, respectively.

鴉片藥物劑量 短效鴉片藥物,如嗎啡和codeine的止痛效果開始於投與後30分鐘,持續大約四小時,因此這些藥物每四小時投與一次。 控釋型口服劑型,如MS Contin的效果開始於投與後1小時,高峰值發生在2~3小時,且持續12小時,因此通常每12小時投與一次。然而有少部分病患(10%~20%)需要每8小時投與。 Durogesic的疼痛緩解效果開始於初次投藥後6~12小時, 高峰值在24~48小時,持續作用72小時。所以, Durogesic貼片通常每72 小時更換一次(有小部份病患需要48小時更換一次) 。 The analgesic effect of short-acting oral opioids such as morphine and codeine begins within 30 minutes after administration and lasts approximately for 4 hours. Therefore these drugs are taken every 4 hours. The efficacy of controlled-release oral formulations such as MS Contin begins within 1 hour, peaks in 2-3 hours, and persists for 12 hours, and thus they are usually taken in 12-hour intervals. A minor group of patients (10%-20%) however may require administration of MS Contin every 8 hours. The pain relief associated with transdermal fentanyl begins within 6-12 hours after initial application, peaks in 24-48 hours, and lasts for about 72 hours. Therefore Durogesic patches are usually replaced every 72 hours (or 48 hours in a small group of patients). Reference: Portenoy RK, Southam MA, Gupta SK, et al. Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology 1993;78:36-43.

口服 Morphine – 劑量調整 常用的起始劑量為短效型嗎啡5-10 mg, q4h 再加上24小時劑量的1/6作為急救劑量。 在第一天完成治療之後,醫師可將患者使用的短效性嗎啡24 小時總計量除以6,而算出調整後的新劑量。 如果臨床上缺乏急救藥物劑量數據,而臨床上患者仍有明顯疼痛時,劑量增加的增幅亦可採用嗎啡每日總劑量的30~50% 。 There is no ceiling for the strong opioids such as morphine and fentanyl. Upward titration should be continued until good pain relief is achieved or uncontrollable adverse effects develop. The commonly used initial dose of morphine (standard release) is 5-10mg q4h, with 1/6 of the total daily dose as the breakthrough dose. Upon completion of the 1st day of treatment, divide the total amount of morphine required in the previous 24 hours by 6, yielding the newly titrated dose of around-the-clock morphine. The breakthrough dose should be updated accordingly. Alternatively, lacking the total dose of breakthrough analgesia, upward titration of morphine may be in 30-50% increments.

長效嗎啡的使用 患者的疼痛在以短效嗎啡獲得足夠的控制兩天後,為提昇患者的醫囑順服性,可將其轉換為長效嗎啡。 將病患過去24小時所投與的短效嗎啡劑量除以2,改為每12小時投與一次MS Contin 。 當實施轉換時,患者只需以MS Contin直接取代下一劑之日夜連續型短效性嗎啡,不必同時服用兩者。 在轉換至口服長效性嗎啡後,醫師仍應繼續給予適當劑量之突發疼痛型藥物。 Once adequate cancer pain control is achieved for at least 2 days with standard release morphine, consider conversion to the same total daily dose of controlled release morphine such as MS Contin so as to enhance compliance. Dividing the total amount of morphine required in the previous 24 hours (ATC + breakthrough) by 2 yields the q12h dose of MS Contin. When transferring patients from standard release morphine to a controlled released formulation, substitute the next dose with the latter directly. It is unnecessary to take both formulations at the same time. Patients taking a controlled release opioid should be given appropriate breakthrough analgesia with standard release morphine as well. Reference: Morphine in cancer pain: modes of administration. Expert Working Group of the European Association for Palliative Care. BMJ 1996;312:823-6.

Transdermal Fentanyl (Durogesic) 可依患者的需要調整劑量,直到順利達成疼痛控制的目標或出現難以處理的副作用。 對從未使用過鴉片類藥物的病患初次投與Durogesic的劑量建議以最小劑量25 µg/h投與,同時合併適量的突發疼痛型藥物,如需要時投與短效型嗎啡5-10 mg(一天投與次數不超過三次)。 There is no ceiling for transdermal fentanyl. Upward titration should be continued until good pain relief is achieved or uncontrollable adverse effects develop. There are more patients to be satisfied with transdermal fentanyl than other opioids in clinical trials. Most patients in clinical trials were converted to Durogesic from other opioids. Therefore, the lowest Durogesic dose, 25 µg/h, should be used as the initial dose in opioid-naïve patients, with the addition of as-needed breakthrough medication such as morphine 5-10mg (use ≤ 3 times/day).

鴉片藥物轉換為Durogesic 1.計算過去24小時口服嗎啡的總劑量,口服嗎啡的劑量為非經腸道吸收嗎啡劑量之3倍(IV), 2倍(SC) 。 2.將口服嗎啡的劑量(mg/day)依照等止痛劑量轉換為Durogesic劑量(µg/h) 常用轉換比例: 口服嗎啡劑量A mg/day= Durogesic A/2 µg/h(最接近者) 例如 oral morphine 60mg = Duragesic 60/2=30, 取 25 µg/h . 3.Durogesic治療期間, 突發疼痛型藥物為步驟1劑量的1/6(or 5~15%), 投與次數每日不超過3次 Use the following steps to switch patients from oral/parenteral opioids to Durogesic : Calculate the total oral morphine dose in the previous 24-hour. Conversion ratio of oral morphine to parenteral morphine = 3:1(IV) or 2:1(SC). Convert this amount (mg/day) to the equianalgesic Durogesic dose (µg/h) base on oral morphine 60mg/day = Durogesic 25 µg/h. During Durogesic therapy, provide oral morphine for breakthrough pain. This rescue dose is calculated to be 1/6 (or 5-15%) of the total daily dose of the fixed-schedule, with a maximum number of administration not exceeding 3 times daily.

鴉片類的副作用 鴉片治療會產生預期性的副作用。在開始治療之前,應和病患針對副作用進行說明。 一些副作用,像是鎮靜,噁心,會隨著時間而消逝,但有一些則會一直持續。 經由適當的治療大部分的副作用都可以得到適當的控制 Opioids have predictable side effects. Discuss them with patients before starting therapy. Some side effects like sedation and nausea may resolve over time, while others persist. With proper treatment, most of them can be effectively managed.

呼吸抑制 少有患者會因接受鴉片類藥物治療而發生具有生命威脅的呼吸抑制現象 病患在投與鴉片類藥物7-10天之後,會出現耐藥性。 給予naloxone治療因鴉片類藥物引起的呼吸抑制時,必須以小幅度的劑量來調整。因naloxone的半衰期很短,所以必須重複地投與(eg: 0.04-0.1mg/1-2 min) ,且小心觀察患者,直至呼吸速率恢復正常為止。 Life-threatening respiratory depression rarely occurs during opioid therapy because patients generally develop tolerance to the respiratory depressant effects of opioids, for example, within 7-10 days,. When naloxone is indicated for the reversal of opioid-induced respiratory depression, it should always be titrated carefully in small increments so that analgesia will not be reversed. Repeated administration of naloxone (eg: 0.04-0.1mg/1-2 min) is often necessary because of its short half-life. The patient should be monitored carefully until normal breathing is restored. Reference: O'Mahony S, Coyle N, Payne R. Current management of opioid-related side effects. Oncology (Huntingt) 2001;15:61-73.

止痛輔助劑 Adjuvant 輔助劑均可應用於癌症疼痛治療的各階段中，與主要止痛劑合併使用 。 如灼痛(burning),刺痛(tingling), 刀刺痛(stabbing),電擊痛(shock-like)或神經病變性疼痛常需要合併輔助劑治療,如抗憂鬱劑或抗痙攣劑。 臨床上，需監測血中藥物濃度以避免產生毒性。 Adjuvants are medications that supplement primary analgesics and can be used at any step of WHO ladder. For example, burning, tingling, stabbing, shock-like, or neuropathic pain usually requires the addition of adjuvants such as antidepressants and anticonvulsants. Need to monitor plasma level for risk of toxicity in clinical practice.

類型 藥名 常用劑量 抗憂鬱劑 amitriptyline 10-150 mg/天 desipramine maprotiline 50-300 mg/天 paroxetine 10-60 mg/天 抗痙攣劑 carbamazepine 100 mg 每天 3 次－400 mg 每天 3 次 valproate 500 mg 每天 3 次－1000mg 每天 3 次 gabapentin 100 mg 每天 3 次－1,000 mg 每天 3 次 clonazepam 0.5 mg 每天 2 次－4 mg 每天 2 次

良好的疼痛控制 評估:較好的評估技巧 信心:使用鴉片類藥物時有較多的信心 知識:對各種止痛藥的了解 平衡:在副作用及止痛效果上取得平衡的能力 The critical message is that the tools are available and there is no reason not to use them. What we need are: 1. Better assessment skills 2. Greater confidence in using opioids 3. Knowledge of the advantages of specific analgesics 4. Ability to balance side effects with efficacy

誌謝 PPTT Members 王玉祥 王全正 王宏銘 王正旭 邱昌芳 巫宏博 林炯森 林哲斌 林勝豐 吳銘芳 高瑞和 張正雄 張明志 張義芳 郭集慶 陳仁熙 陳彥仰 陳博明 曹朝榮 黃文豊 黃文聰 黃承華 黃叔牧 黃明立 葉士芃 葉光揚 馮盈勳 葉坤輝 趙大中 蕭士銓 蕭惠樺 鄭丞傑 劉青山 謝瑞坤 謝長堯 顏家瑞