Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain

  • Review
  • Intervention

Authors

  • Philip J Wiffen,

    Corresponding author
    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
    • Philip J Wiffen, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. phil.wiffen@ndcn.ox.ac.uk.

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  • Sheena Derry,

    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
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  • R Andrew Moore

    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
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Abstract

Background

There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway (LCP) in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The resulting Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".

The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient.

Objectives

To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain.

Search methods

We assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl, oxycodone, and codeine.

Selection criteria

We included randomised studies using multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine) in cancer pain. These were taken from four existing or ongoing Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles.

Data collection and analysis

Two review authors independently extracted adverse event data, and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness, appetite, and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium, dizziness, hallucinations, mood change and somnolence relating to patient consciousness, and nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia, asthenia, dehydration, or dry mouth relating to appetite or thirst.

Comparative measures of harm were known to be unlikely, and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid, and for all four opioid drugs combined.

Main results

We included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used.

Direct measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below.

Authors' conclusions

We found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine.

We are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.

摘要

在癌症疼痛控制時,嗎啡、fentanyal、oxycodone或codeine對病人意識、食慾和口渴的影響

背景

提供病人生命末期的高生活品質,逐漸被大家所重視,不論是在疾病本身或是引起的原因,和整體的安排。最近十年來,對於末期病患的照顧途徑普遍在全世界受到重視。英國Liverpool Care Pathway(LCP)的臨床照顧途徑已遭受批評。在英格蘭Liverpool Care Pathway(LCP)是獨立項目,由衛福部長審核。Neuberger審查聲明結果表示,LCP在基礎上提供了良好的優質護理服務、為患者及家屬實施正確的道德原則。LCP的往往沒有適當的執行,反而成為造成好品質的一個障礙。超過40項建議,包括教育和培訓,研究和開發,獲得專科緩合治療服務,並需要確保關心和同情所有臨終病人。2013年7月,衛生部發布了規定,LCP的應用“在未來6-12個月應逐步淘汰,取而代之為對每一個病患以個人化的臨終護理照護”之聲明。

鴉片類藥物的使用過去被高度的關注,因為此藥物可能影響末期生命的病人其意識、食慾和口渴情況。有人擔心,患者知覺受損會導致死亡的提早,食慾和口渴的情況將受鴉片類藥物的影響,可能會導致不必要的痛苦。委託國家衛生研究院的快速的回顧,採用標準的Cochrane方法學來研究癌症疼痛時,嗎啡,fentanyl, oxycodone, 和 codeine的不良影響;這些藥物在臨終病人可能產生的影響非常接近。

目的

對於癌症病患的疼痛,以隨機對照試驗為研究方式,其鴉片類,像是:嗎啡、fentaanyl 、oxycodone 和codeine 在意識狀態、食慾或是口渴的影響。

搜尋策略

我們評估被報導Cochrane系統中的鴉片類藥物,發生於癌症疼痛不良事件的數據,包括:嗎啡,fentanyl, oxycodone, 和codeine。

選擇標準

我們採納隨機複合使用四種類型嗎啡類的藥物(morphine, fentanyl, oxycodone, and codeine)來控制癌症疼痛。這些都是從四個現有或正在進行的Cochrane回顧搜尋。參加者是年滿18歲以上的成人。我們只採納全期刊發表的文章。

資料收集與分析

兩位回顧作者獨立的萃取不良事件,並檢查研究品質的問題。主要結果是統計參加者有經歷到意識情況變差、食慾不振及口渴的不良事件發生的數量。次要結果的結果有可能主要結果所產生的影響:譫妄、頭暈、幻覺、情緒變化、嗜睡、噁心、嘔吐、便秘、腹瀉、消化不良、吞嚥困難、厭食、乏力,脫水或與口乾相關的食慾或口渴變化。

去測量以上這些有害症狀是不太可行,因此,我們計算參與者有體會到每一種鴉片類不良事件的比例,或是四種鴉片類藥物合用下的情況。

主要結果

我們納入77個試驗,5619隨機的參與者。大多數研究都有其潛在偏差,樣本數小是最常見的,個人化且不到50人參加的試驗,佔有60個研究。參與者比較年輕,平均年齡介於50至70歲。多個主要不良事件被報告,包括在全部的病人中,用藥有藥物副作用狀況者之闕漏通報、所有曾經經歷的藥物副作用事件、藥物副作用發生後如何進行收集、無定義藥物副作用的術語或是完整的通報系統。

無法直接量測病人的意識、食慾,或是口渴情況。對於治療癌症疼痛的藥物副作用的發生率,分別為使用鴉片類藥物後發生便秘25%、嗜睡23%、噁心21%、口乾17%,至於嘔吐、厭食和頭暈各為13%。乏力、腹瀉、失眠、情緒改變、幻覺和脫水各為5%以下發生率。

作者結論

我們沒有發現任何直接的證據證明,在用於治療癌性疼痛時,鴉片類藥物會影響患者的意識、食慾或口渴情況。然而,在對癌症疼痛病患使用嗎啡、fentanyl、oxycodone或是codeine,其嗜睡、口乾和厭食則是常見的藥物副作用。

我們都知道報告藥物副作用的存在原因相當重要。合併使用合併症的藥物、數據的收集、報導及命名。這意味著藥物的副作用,總是被不能明確地歸因於使用鴉片類藥物,因此鴉片類藥物在癌性疼痛上副作用藥物僅是一個概略性的想法。該研究議程包括發展定義於藥物副作用的嚴重性和重要性,以及發展合適的監測方式,來記錄這些藥物副作用,以幫助臨床和臨床研究的藥物副作用的定義。

譯註

翻譯者:臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw

Plain language summary

Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain

Description of the problem

Care pathways are packages of care designed to ensure that patients have appropriate and effective care in particular situations. Such pathways are commonly used, and often produce good results, but they can also be used as a tick box solution that acts as a barrier to good care. Care pathways have been used to ensure appropriate care for people who are dying in hospice settings.

The Liverpool Care Pathway was devised for use in hospices, and has been used in general hospital settings to care for dying patients. Its use has been criticised. A government review of the use of end-of-life care pathways in the NHS in the UK recommended they should not be used because they were being misused.

A concern, mainly raised by relatives, was that opioids were over-prescribed, used to hasten death, to reduce consciousness, and diminish the patient's desire or ability to accept food or drink.

The purpose of this review

This Cochrane review was commissioned to look at harms (adverse events) associated with the use of opioids to treat cancer pain particularly relating to patient consciousness, appetite or thirst.

How the information was gathered

Ideally, when writing this review we would have looked at medical trials of opioid use in older people receiving end-of-life care, but there are no trials in this area. So, we looked at trials of people being treated with opioids for cancer pain, as the
information these trials provide is likely to be the closest that is available to opioid use in end-of-life care - although people treated for cancer pain are not usually at the end of their lives.

What we found

This review identified 77 studies with over 5,000 people who received various treatments. The population in these trials was mainly aged between 50 and 70 years. Trial quality was generally poor; particular problems included small study size, and not reporting adverse events in all patients, or all recorded adverse events. Known problems with adverse event measurement, recording, and reporting made assessment even more difficult.

For all four opioids together, 1 in 4 people experienced constipation and somnolence (sleepiness, drowsiness), 1 in 5 experienced nausea and dry mouth, and 1 in 8 experienced vomiting, loss of appetite, and dizziness. Weakness, diarrhoea, insomnia (difficulty in sleeping), mood change, hallucinations and dehydration occurred at rates of 1 in 20 people and below. These results may contribute to understanding the effects of opioids on consciousness, appetite, and thirst in end-of-life care in all patients deemed to be people who are dying.

淺顯易懂的口語結論

在癌症疼痛控制時,嗎啡、fentanyal、oxycodone或codeine對病人意識、食慾和口渴的影響

問題的敘述

照護途徑是一方案,旨在保證病人在特定情況下,有適當和有效的照護。這樣的途徑經常的被使用,通常效果也相當的好,但也將會像是核取方塊選單,造成達到優質照護品質的障蔽。照護途徑過去被用來確保快要瀕臨死亡的病人,有一個適當的照顧的安寧制度。

Liverpool照護途徑被設計用於在安寧,並且已經被綜合醫院所使用,以照顧臨終病人。其制度一直廣受批評。英國政府回顧在NHS的生命末期病人的照護途徑,建議不應該被使用,因為被濫用。

另一個被關注的問題是關連性,過去都會過度使用鴉片類藥物,變成加速病人的死亡,意識的喪失,並減少患者進食或是飲水的能力。

此回顧的目的

該Cochrane回顧是被委託,確認鴉片類藥物治療癌症疼痛病人,與其意識情況,食慾或口渴相關性的危害(藥物副作用)。

如何收集訊息

理想情況下,寫這篇回顧時,我們需要看對於末期老年人在的鴉片類醫學試驗,但也沒有這方面的試驗。所以,我們看鴉片類藥物用於癌症疼痛治療的臨床試驗,這些試驗提供的信息很可能是最接近鴉片類藥物運用在生命末期照顧的,儘管人們治療癌症疼痛通常不會在其生命的終點。

我們發現什麼

確定77個研究,當中有超過5,000人接受過各種的治療。在這些試驗中,主要的年齡是介於50歲至70歲之間。試驗的品質普遍較差;具體的包括樣本數規模小、在所有病人中沒有藥物副作用的報告,或全都是記錄藥物副作用。對已知問題的藥物副作用測量、記錄和報告並做出評估更加困難。

對於將四種鴉片類藥物一起使用, 4個人當中有1人有便秘、嗜睡(想睡,有睡意),5個人當中有1個人有噁心、口乾的感覺,8當中有1人有嘔吐、食慾不振和頭昏。虛弱、腹瀉、失眠(不易入睡),情緒改變、幻覺和脫水會,在20個人當中會有1個人或是比例更低。這些結果可能有助於釐清鴉片類的藥物,是否真的會影響生命末期病人或是知道自己即將瀕臨死亡的病患其意識情況、食慾、口渴情況。

譯註

翻譯者:臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw