星期二, 12月 13, 2005

Pharmacologic Management of Chronic Back Pain

這是我在醫學會報告過的題目,我相信很多醫師,特別是骨科醫師,會開給病人止痛的藥物,大概僅限於非類固醇的消炎止痛藥、普拿疼和肌肉鬆弛劑。 其實不只如此。但如果一看到就要病人住院,明天開刀的骨科醫師,大概一方面不需要懂得如何用藥,另一方面不會尋求這樣的知識吧! 所以我放在這裡,希望有興趣的病人,能夠發現,順便提醒你的醫師。


Pharmacologic Management of Chronic Back Pain
慢性背痛的藥物治療

Before we start…
教授的吩咐
– “以前我也去過貴院支援一段時間, 如果你看到我開刀的病例, 請…“ 意思是如果萬一遇到什麼不甚妥當的,可以幫他好好解釋一下。

其實沒有一個醫師能治好所有他的病人,無論手術或非手術。 另外這篇文章中的疼痛治療,不只針對背痛有效,其他比如退化性關節炎,骨骼肌肉傷害都是一樣的原則。

Chronic (Low Back) Pain 的藥物治療,參考資料
Reference: AAOS Spine Update 2 2002年版本
Basic & Clinical Pharmacology, 2001年版本
健保藥價表

Chronic Pain慢性疼痛的定義
Current difinition: Pain that lasts longer than would be expected for healing of the original injury to take place or as pain associated with progressive, nonmalignant disease 目前的定義是疼痛持續,超過了造成疼痛的傷害預期應該經痊癒的時間,或者漸進性,非惡性疾病造成的疼痛

Formally: pain that lasts more than 6 months 從前認為疼痛超過六個月算是慢性疼痛

Statistics統計數字
10% pt with back pain do not get better in 4 – 6 wks 有百分之十的病人背痛會轉為慢性
> 50% pt recover and recur 這些慢性背痛的病人有超過一半其疼痛反覆發作
Some are destined to develop chronic back pain 有些人註定會成為慢性疼痛的患者

Etiology病因
Complex medical condition: both physical and psychosocial factors 病因複雜未有定論
85% pt with LBP cannot be given a definitive diagnosis 有百分之八十五的背痛病人無法下確定診斷
Poor associations among symptoms, physical findings and imaging results 背痛的診斷,與症狀,理學檢查和影像學發現,彼此的關聯性很低。

What frequently happened in the OPD在門診常常會有這樣的對話
Patient:“Doc, I feel back pain all the time…”病人說:醫生,我的背一直痛
Doc might say, if 你的醫生會這麼回答,如果:
– X-ray normal: that’s just kinda soreness X光片是正常的:只不過是筋骨酸痛而已
– Healed compression fr.: residual pain 發現有些以前的壓迫性骨折:殘餘的痛嘛!
– Op by other surgeon: I don’t know actually what happened during your last operation 如果別的醫師開過的刀: 我沒辦法判斷到底別的醫師開刀有沒有遇到什麼狀況

When facing intractable, refractory, disable chronic back pain 如果病人的痛很頑固,很嚴重,很失能
Doc.: “Pt might have psychological problem.”醫師會想:搞不好是心理的因素

Pt: 病人會說:你講自費手術效果更好, 結果還是痛得不得了! (醫師你糟糕了,要病人自費結果病人沒好!)

對醫師和病人,慢性背痛的治療都很具挑戰性。

Chronic Refractory spinal Pain, 3 types 慢性背痛分三種
Nociceptive pain 疼痛受器的痛
Neuropathic pain 神經受損的痛
Mixed 混合型

Nociceptive Pain 疼痛受器的痛
Structural disorder stimulating small n. endings(nociceptors)由於組織構造的病造成周邊疼痛受器受刺激引發痛覺
Painful discs 比如 椎間盤破損的疼痛
Most responsive to Opioids, NSAIDs, tricyclic antidepressants (tricyclics, TCAs) 這樣的疼痛用鴉片類製劑,非類固醇消炎止痛藥和三環抗憂鬱劑有效


Neuropathic Pain 神經受損的痛

Caused by n. damage or injury 由於神經受損或受傷引起的痛覺
N. sensitized, minimal stimulation causes pain 有時神經被致敏化,即使小小的刺激都會造成很大的疼痛
比如 Battered root, arachnoiditis, complex regional pain syndrome( RSD)
Drugs of choice: TCAs, anticonvulsants 這種痛用三環抗憂鬱劑和抗癲癇藥物治療有效

Analgesics 哪些藥可以止痛
Centrally acting analgesics作用在中樞的
– Opioids 鴉片

Peripherally acting analgesics作用在周邊的
– Acetaminophen, aspirin, NSAIDs 普拿疼,阿斯匹靈,非類固醇消炎止痛藥
– Mild to moderate pain 輕度到中度的痛有效
– Often ineffective 對慢性背痛往往無效
– Mechanism: other than anti-inflammation 作用機轉: 不是抗發炎,因為抗發炎作用出來之前, 已經有止痛效果
– Selection: by speed of onset and duration of onset 選擇哪一種依藥物的生效速度和持續時間決定
- 如 voltaren, voren, celebrex, mobic, nimed, ibuprofen, ketoprofen, clinoril 等等

Opioids鴉片類製劑
Binding to opiate receptors in the CNS 作用機轉:鍵結到中樞神經系統的鴉片接受器
Morphine, fentanyl, codeine, methadone, oxycodone… 嗎啡,fentanyl,可待因,等等
Best for nociceptive pain 對於疼痛受器的痛最有效
Insensitive: neuropathic pain, movement related pain 但是對於神經受損的痛比較沒效,活動才會痛,而靜止不痛的痛比較無效

Controversy關於鴉片製劑有非常多爭議
Long-term use of opioids for chronic pain 長期用到底會如何?
Less controversy than 10 yrs ago 但較十年前爭議少了
Many physicians use opioids for chronic LBP, OA & painful musculoskeletal
disorders 目前已經有很多醫師使用鴉片製劑治療下背痛,退化性關節炎和骨骼肌肉疾病(這裡說的當然是北美啦)

Concerns about the use of opioids 顧慮
Concerns about producing addiction & dependence 成癮性和依賴性
Fear of causing organ intoxicity 器官毒性如何
Apprehension about possible displinary action by medical licensing boards 會不會被醫學會懲誡
Concerns about the tolerance 耐受性,長期用會不會劑量必須一直增加才有效?
Drug efficacy 有效嗎

Long-term use of opioids 長期使用鴉片類製劑
Efficacy and safety 效能及安全性
– Evidence published: long-term opioid therapy can be safe and effective in well-selected patients with LBP & OA 發表的文獻支持對背痛及退化性關節炎,鴉片類安全且有效
– No study: lack of efficacy 沒有人說無效
– No evidence of serious organ intoxicity or of high incidence of addictive behavior or abuse 沒有人證明有嚴重的器官毒性或者很高的機會出現成癮行為和藥物濫用

Long-term use of opioids 長期使用鴉片類製劑
Side effect 副作用
– 40% constipation, 40% nausea, < 40% dizziness 便秘,噁心,頭暈的機會各約40%
– 15% pt unable to tolerate 有15%的病人受不了副作用
Efficacy 效用
– 75% pt got meaningful pain relief 有75%病人表示獲得顯著的止痛效果
– Most increased in function 大部分人生活上的功能進步了
– 10% disabled pt: return to work 有10%失能的病人甚至可以回到工作崗位

Concerns about opioids
Addiction 成癮
– Addiction is a primary, chronic, neurobiological disease, with genetic psychosocial, and environmental factors influencing its development and manifestation. It is characterized by behaviors that include the following: impaired control over drug use, craving, compulsive use, and continued use despite harm. Physical dependence and tolerance are normal physiological consequences of extended opioids therapy for pain and are not the same as addiction
成癮是一種原發、慢性、神經生理性的疾病,其發生及展現形式受到遺傳、社會心理及環境因子的影響。其典型行為包括:無法控制的過量藥物使用,即使有害也仍然不斷強迫性的渴求其使用。藥物的耐受性及生理依賴性,是持續使用鴉片類止痛劑的正常結果,不等同於成癮。

Concerns about opioids

Tolerance 耐受性
– A physiologic state resulting from regular use of a drug in which an increased dosage is needed to produce a specific effect, or a reduced effect is observed with a constant dose over time. Tolerance may or may not be evident during opioid treatment and does not equate with addiction.
Concerns about opioids
耐受性是一種因規律使用藥物,而使藥效發揮之所需劑量不斷增加或劑量不變但藥效下降之生理狀態。鴉片類止痛劑治療過程中,耐受性不見得會顯著發生,而且不等同於成癮。

Physical Dependence 生理依賴性
– A state of adaptation that is manifested by drug class-specific signs and symptoms that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Physical dependence, by itself, does not equate with addiction.
生理依賴性是一種生理適應狀態,徵兆及症狀具有藥物專一性,突然停藥、急劇降低劑量、血液藥物濃度降低、施用拮抗劑都會導致症狀出現。生理依賴性本身並不等同於成癮。

Disciplinary action 醫師處方會遭遇的法規和規範

Federation of State Medical Boards of the United States
– Model Guidelines for use in regulating the prescribing of controlled substances for the management of pain, 1998
管制藥物用於疼痛治療之模式準則,1998年聯邦醫藥委員會提出,2004年改版如下。

– Model policy for the use of controlled substance for the treatment of pain, 2004
管制用藥用於疼痛治療之模式政策,在本blog裡面已經翻譯為中文

衛生署管制藥品管理局,2002
– 醫師為非癌症慢性頑固性疼痛病患使用成癮性麻醉藥品注意事項
詳細條文請在google上搜尋很容易找到。 國內的法規還比較屬於古早,原始的觀念。以管制藥品為優先,而不是用於疼痛治療為優先。

Requirement for Rx 要用鴉片類製劑必須審慎
Careful evaluation of pt 小心評估病人
Written treatment plan 寫下治療計劃
Informed consent 病人簽同意書
Periodic review and document efficacy, side effects, and problems 定期檢討並報告藥效,副作用和問題
Consultation 會診精神科和疼痛科

Dosing Intervals 投藥的間隔
– Pain-contingent 痛了用
– Time-contingent (V): avoid large swings in blood or brain levels 時間到了用,可避免血中和腦中藥物濃度大幅波動
– Short-acting vs. long acting 長效藥物比較不會造成藥物濃度大幅波動
Continuous-release or long acting preferred 理想中應該是定時服用,長效型藥物

Choice of Opioid Analgesic 選擇鴉片類製劑
– No one drug is best for every pt 最好的藥每個人不一樣
– Morphine 嗎啡
Multiple dose size, convenient 有各種劑型,劑量,途徑,使用最方便
Morphine 10mg q4-6h, Morphine-SR 30mg, 60mg

– Codeine 可待因,很多咳嗽糖漿也有,是短效的
Short acting 15-60mg q4-6
– Fentanyl 可以做成皮膚貼片 durogesic,超長效,可維持三天
transdermal 25ug, 50ug/h Q3DE

Route of administration and doses 投予途徑和劑量
– In chronic pain: long-acting, oral or transdermal 慢性疼痛用長效,口服和貼皮膚為妥
– Immediate release for breakthrough pain or flares 有時會有爆發性的疼痛,需給速效,短效的藥物
– Dose and interval adjusted based on the efficacy and side effect 依照效能和副作用調整劑量和間隔
– There is no best or correct dose 無所謂最好或正確的劑量

Side Effects 副作用
Somnolence and change in mental status 昏睡,精神狀態改變
Cognitive abilities actually improve after pain relieved by opioids 有些老人家痛久了,失去求生意志,讓他去,用了這藥不痛了,其認知能力反而進步,不昏睡
Excessive sedation: Ritalin 過度昏睡可用此藥解除,是中樞興奮劑
Nausea: Novamin or transdermal scopolamine 噁心的解藥
Constipation: prophylaxis 便秘就用些軟便劑
Itching, sweating, dry mouth, dizziness, sexual dysfunction 此外還有皮膚癢,盜汗,口乾,頭暈,性功能異常的副作用

Antidepressants 抗憂鬱劑,此介紹其止痛效果,不當抗憂鬱使用
Chronic spinal problems: neuropathic pain, sleep disturbance, and depression 對慢性背痛,神經受損的疼痛,睡眠障礙,憂鬱症有效
Most effective for neuropathic pain & LBP 對神經受損的痛及下背痛最有效
TCAs work better for pain, low dose 三環抗憂鬱劑 (TCA) 在低劑量時,止痛比抗憂鬱效果好
SSRIs better for depression 含有血清素再回收抑制劑(SSRI)的憂鬱症藥物止痛效果不好

Mechanism 作用機轉
TCAs: block the presynaptic reuptake of norepinephrine 抑制突觸前正腎上腺素的再回收
SSRIs: block reuptake of serotonin 抑制血清素的再回收
MAOI: not for chronic pain MAOI對治療慢性背痛沒有幫助

Choice of Antidepressant 抗憂鬱劑的選擇
Choice depending on the target symptoms 針對要治療的症狀
– pain, depression or sleep disturbance 主要是疼痛,憂鬱或睡眠障礙
TCAs nortriptyline, desipramine, and amitriptyline: most effective for pain 這三種TCA對止痛效果很好
SSRIs fluoxetine, sertraline … most useful for depression 這幾種SSRI是標準治療憂鬱症的藥物

Some antidepressant considerations for patients with chronic pain 抗憂鬱劑藥物的給法
Dosing Guidelines 劑量指引
TCAs above: initial 5mg QN, increased every 5 days in 10-mg incr. to 50mg 上述的TCA一開始每晚給5毫克,每五天增加十毫克,到50毫克
Then increase in 25 incr to target 75 or 100mg 然後一次增加25毫克到75至100毫克
SSRIs: Prozac start 20mg in the morning, Zoloft 50mg SSRI也是漸漸增加劑量

Side Effects 副作用很多,請注意
Common, vary in intensity 很常見,但程度差異很大
TCAs: sedation, insomnia, orthostasis, anticholinergic TCA會導致嗜睡,或者失眠,orthostasis,以及抗副交感神經的作用,如視力模糊,口乾,竇性心搏過速,便秘,小便瀦留,記憶力失常
– Blurred vision, dry mouth, sinus tachycardia, constipation, urinary retention, and memory dysfunction
Relative side effects of commonly used antidepressants 這些副作用常用的抗憂鬱劑都常見

Anticonvulsants 抗癲癇藥
Can be effective for neuropathic pain but rarely for LBP 對於神經受損的痛有效但下背痛無效
Gabapentin: used most often, but off label use 這個藥我的醫院沒有,但美國處方量非常大,卻是非標籤註明的使用法
– Iatrogenic nerve injury, arachnoiditis, or prolonged neural compression and for peripheral neuropathy 醫源性的神經損傷,硬腦膜炎,已經很久的神經壓迫,周邊神經病變

Clonazepam(Rivotril 2mg), a benzodiazepine 這個藥是目前比較安全,副作用少的藥
– For neuropathic pain 神經損傷的痛
– Effective in reducing myoclonic jerks 可減少肌陣攣

Carbamazepine( tegretol), sodium valproate(depakine), phenytoin (dilantin)
– Helpful but potential for serious side effect 這幾個藥我不建議用因為有潛在重大的副作用,比如再生不良貧血,肝功能障礙等等。

Muscle Relaxant 肌肉鬆弛劑
Acute LBP: muscle spasm, sprain, strain 急性的痛可以減少痙攣(號稱)
Chronic LBP: muscle involvement 2nd to an underlying structural problem
Use for Chronic LBP limited 治慢性的痛角色有限
Evidence(X) 沒有證據證明有效,可以丟進垃圾桶了
Baclofen: painful spasm, neuropathic pain 說是這麼說,我不信baclofen, befon有啥效

Sedative-hyponotics 鎮靜安眠藥
The role is limited 不拿來當止痛用
– Zolpidem ( stilnox ) 這是書上說最安全的安眠藥
Safest drug
Less likely dependence, rebound insomnia, or daytime sedation 比較沒有依賴性
Long-term use is problematic 長期的問題還是質疑
– Cognitive impairment
– Depression
– Rebound insomnia


Miscellaneous Drugs 其他奇奇怪怪的藥
Antihistamines 抗組織胺
– For opioid-induced nausea, vomiting, and itching 對鴉片製劑引起的噁心,嘔吐和癢有效
– Do not enhance opioid analgesia 對鴉片製劑的止痛效果沒有加成效果
Topical analgesics 藥膏,我看算了吧!
– Capsaicin: depleting substance P in small nociceptors
– Lidocaine 5% patch

Summary 總結
Chronic (low back) pain 慢性(下背)痛
– Pain persists even injury healed 痛持續,即使受傷已癒
– Difficult to management 難處理
– Reasonable expectation 要請病人對治療的成效,抱持合理的預期,意思是別想得太美好
Nociceptive pain vs. neuropathic pain 這兩種不同的痛,藥物不同

Summary 總結
Nocicpetive pain 疼痛受器造成的痛
– Opioids, NSAIDs, tricyclics 一線藥物是鴉片,其次是消炎止痛藥,三環抗憂鬱劑
– Morphine, fentanyl, mobic, tryptanol, imipramine 這是我的選擇(Editor's Choice!)
Neuropathic pain 神經受損的痛
– tricyclics, anticonvulsants, Opioids 三環抗憂鬱劑為首選,其次是抗癲癇藥物,鴉片
Mixed pain syndrome 混合型,藥物就看情況用

Summary 總結
Opioids are safe and effective in well-selected patient 鴉片類是安全有效的藥物
Beware of the current regulations which has been out-of-date 請醫師和患者都要當心目前國內還比較原始,跟不上現代醫學腳步的法律規範

6 則留言:

匿名 提到...

Can I ask doctor a question what kind of Chronic Refractory spinal Pain about me?

I think the answered is mixed.

I don't know wethear it true or not.

By you know me.

hbrk55 提到...

I am not really sure who you are.

A typical neuropathic pain is caused by burst fracture, in which the nerve fibers were damaged during trauma.

For you, I think you have more nociceptive pain. The unbalanced muscle tones at both side of the vertebrae are opt to cause the pain.

Actually most pain are sort of mixed type. Especially in case the pain has a long history.

匿名 提到...

沒想到醫師一下子就翻譯了那麼多了!呵...辛苦您了!

去年的我,曾被歸類為心理作用,導致術後疼痛。

甚至給我會了精神科,我還告訴醫生,我沒有病我媽才有病!


現在想起來真的有些荒謬。我的母親看到這篇文章後還有最近的發現後,發現他錯了。

不該這樣想,當初應該怎樣...

但這些已成雲煙,過去的就讓他過去吧!

未來的幾個月中,我會朝向紀錄我20年人生出書的目標!

匿名 提到...

看到您認真的翻譯,獻上我的敬仰之意,真是個好醫師

隊員

hbrk55 提到...

總算翻譯完成了!

沒辦法,醫師不唸書,只好教育病人了。

匿名 提到...

假若出現管制藥物戒斷症時,醫師會怎樣處裡?我知道患者沒有心理依賴,但是他的生理卻很依賴,現今的他每天都會打呵欠、流鼻水、流淚等。應該如何幫助他呢?