Ketamine as an adjuvant to opioids for cancer pain

  • Review
  • Intervention

Authors

  • Rae F Bell,

    Corresponding author
    1. Haukeland University Hospital/University of Bergen, Institute of Surgical Sciences/Regional Centre of Excellence in Palliative Care, Bergen, Norway
    • Rae F Bell, Institute of Surgical Sciences/Regional Centre of Excellence in Palliative Care, Haukeland University Hospital/University of Bergen, Bergen, N-5021, Norway. rae.bell@helse-bergen.no. raeb@frisurf.no.

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  • Christopher Eccleston,

    1. Centre for Pain Research, University of Bath, Cochrane Pain, Palliative and Supportive Care Review Group, Bath, UK
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  • Eija A Kalso

    1. Helsinki University Central Hospital, Department of Anaesthesia and Intensive Care Medicine, Helsinki, Finland
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Abstract

Background

This is an update of the original review published in Issue 1, 2003. Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is known to have hallucinogenic side effects.

Objectives

To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain.

Search methods

Studies were identified from MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CancerLit (1966 to 2002), T he Cochrane Library (Issue 1, 2001); by handsearching reference lists from review articles, trials, and chapters from standard textbooks on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis) provided search results from their in-house database, PARDLARS.

An improved and updated search of the following was performed in February 2007: Specialized Register of the Cochrane Pain, Palliative and Supportive Care group (PaPas), CENTRAL, MEDLINE & OVID MEDLINE R, EMBASE, PubMed (Limit to cancer subset),The Pfizer Product information database. In addition, the Cochrane database of systematic reviews was searched in April 2007.

Selection criteria

RCTs of adult patients with cancer and pain being treated with an opioid, and receiving either ketamine (any dose and any route of administration) or placebo or an active control.

Data collection and analysis

Two independent review authors identified four RCTs for possible inclusion in the review, and 32 case studies/case series reports. Quality and validity assessment was performed by three independent review authors, and two RCTs were excluded because of inappropriate study design. Patient reported pain intensity and pain relief was assessed using visual analog scales, verbal rating scales or other validated scales, and adverse effects data were collated.

Main results

No new trials were identified by the updated search. Two trials were eligible for inclusion in the original review and both concluded that ketamine improves the effectiveness of morphine in the treatment of cancer pain. However, pooling of the data was not appropriate because of the small total number of patients (30), and the presence of clinical heterogeneity. Some patients experienced hallucinations on both ketamine plus morphine and morphine alone and were treated successfully with diazepam. No other serious adverse effects were reported.

Authors' conclusions

Since the last version of this review no new studies were found. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More randomized controlled trials are needed.

摘要

背景

使用Ketamine作為鴉片類藥物(opioids)用於治療癌症疼痛之佐劑

這是一篇發表於2003年第一冊重新修訂的原創之翻譯文獻評論。Ketamine是一種常用的麻醉劑,當鴉片類藥物單獨使用治療癌症疼痛無效時,麻醉劑量下的Ketamine常被作為鴉片類藥物治療癌症疼痛時的佐劑。已知Ketamine具有幻覺的副作用。

目標

確立使用Ketamine作為鴉片類藥物治療癌症疼痛時之佐劑的效用與不良影響。

搜尋策略

我們收尋了MEDLINE(1966年至2002年),EMBASE(1980年至2002年),CancerLit(1966年至2002年),The Cochrane Library (Issue 1, 2001);並以手工查閱並摘選標準的教科書中有關疼痛護理和姑息治療之評論文章、試驗之章節參考清單,再從以上資料庫系統所檢索確定的文獻。ketamine製造商(Pfizer ParkeDavis)所提供的結果從他們的公司內部數據庫PARDLARS搜索出來。在2007年2月有更新進的搜索:Specialized Register of the Cochrane Pain,Palliative and Supportive Care group (PaPas), CENTRAL,MEDLINE & OVID MEDLINE R,EMBASE, PubMed(僅限癌症),The Pfizer Product information database。除此之外,還收尋2007年4月the Cochrane database of systematic reviews。

選擇標準

我們收納對象是採隨機對照試驗方式收集有罹患癌症疼痛且接收鴉片類藥物治療,不論是同時接受ketamine(任何劑量和任何給藥途徑)或是安慰劑、或主動疼痛控制的成年病患。

資料收集與分析

我們收納了了兩個獨立評論作者所確定的了4個隨機對照試驗,和32個病例分析/病例系列報告。由三個獨立的評論作者進行質量和有效性的評估,其中有兩個隨機對照試驗因為研究設計不適當而被排除在外。使用視覺模擬尺度,口頭評定量表或其他經過驗證的量表來評估病人的疼痛強度和疼痛緩解情形,並收集整理不利影響的數據。

主要結論

最新的搜索中尚無新的試驗被確立。有二項合於原創之評論皆認定:ketamine具有促進嗎啡在治療癌症疼痛的成效。不過,總患者人數(30)過小,匯集這樣的數據在呈現臨床異質性是不恰當的。有些病患在接受嗎啡單獨治療或嗎啡合併ketamine治療時,皆出現幻覺的現象,而此情形可以成功的使用diazepam治療。其他尚無嚴重的不利影響被報導。

作者結論

自上次版本的評論至今還沒有新的研究發表。目前的證據不足以評估ketamine作為鴉片類藥物的佐劑來治療癌症疼痛的好處和害處,需要更多的隨機對照試驗加以證實。

翻譯人

本摘要由三軍總醫院謝凱芝翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

使用ketamine合併疼痛殺手,如嗎啡,用於治療癌症疼痛的益處和害處,目前尚未建立。嗎啡類藥物(鴉片類藥物),經常被用來治療中度和重度癌症疼痛,但在某些情況下,這些藥物卻不能奏效。Ketamine是一種麻醉劑,當鴉片類藥物單獨使用治療癌症疼痛無效時,經常合併使用Ketamine以促進鴉片類藥物的止痛效果。然而,事實証明這種做法的有效性是有限的。兩個小試驗表明ketamine與嗎啡合用,可能有助於控制癌症疼痛。不過,這些數據仍是不足以評估此種治療的成效。

Plain language summary

Ketamine as an adjuvant to opioids for cancer pain

The benefits and harms of adding ketamine to strong pain-killers such as morphine for the relief of cancer pain are not yet established. Morphine-like drugs (opioids) are frequently prescribed for moderate and severe cancer pain, but in some cases these drugs are not effective. Ketamine, an anaesthetic agent, is used to improve analgesia when opioids alone are ineffective. However, evidence for the effectiveness of this practice is limited. Two small trials suggest that when ketamine is given with morphine it may help to control cancer pain. However, these data are insufficient to assess the effectiveness of ketamine in this setting.

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