Ketamine as an adjuvant to opioids for cancer pain

R Bell, C Eccleston, E Kalso
Cochrane Database of Systematic Reviews 2003, (1): CD003351

BACKGROUND: 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. To date no systematic review of the benefits and harms of adjuvant ketamine for cancer pain has been undertaken.

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 (1966-2001), EMBASE (1980-2001), CancerLit (1966-2001), the 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.

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 reviewers 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 reviewers, 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: Two trials were eligible for inclusion in the 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.

REVIEWER'S CONCLUSIONS: 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.

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