Ketamine as an adjuvant to opioids for cancer pain

Bell RF, Eccleston C, Kalso EA

Published Online:

July 8, 2009

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.

Abstract (click to read)

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 strategy:

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.

This record should be cited as:

Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003351. DOI: 10.1002/14651858.CD003351

Assessed as up to date:

June 19, 2007

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Primary Review Group:

Pain, Palliative and Supportive Care Group

Health topics:

Cancer > Palliative and supportive care > Symptomatic relief

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Ketamine as an adjuvant to opioids for cancer pain

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