Bell, R.F., Eccleston, C., & Kalso, E.A. (2012). Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD003351.

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

Databases searched were CENTRAL, MEDLINE, EMBASE, PubMed, and the Pfizer Product Information Database.

Studies were included in the review if they

• Were randomized clinical trials (RCTs).
• Involved adult patients with cancer pain being treated with opioids.
• Studied patients receiving ketamine at any dose or route for cancer pain or a placebo or active control.

Studies were excluded if they had fewer than 10 participants.

A total of 120 references were retrieved. Studies were selected based on criteria, assessed independently, reviewed by two reviewers, and chosen for inclusion by three independent reviewers.

• The final number of studies included was two.
• The total number of patients included in the review across studies was 30.
• Of these patients, 20 were hospitalized with cancer pain unrelieved effectively with opioids who received two different doses of IV ketamine (0.25 mg or 0.5 mg) and 10 were patients with neuropathic pain unrelieved by opioids.

• Patients were at the end-of-life phase of care.
• This study has clinical applicability for palliative care.

• For IV ketamine, the 0.5 mg dose demonstrated a significant reduction in pain intensity and the relief was sustained throughout the three-hour measurement period.
• For intrathecal ketamine, pain was controlled on reduced doses of intrathecal opioids or on ketamine alone.

Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids in the relief of cancer pain because of the small number of trials with low sample sizes.

• The sample size was small, with only 30 patients.
• Few RCTs exist on this topic.
• Doses and routes of administration of ketamine were different, measurement of pain was variable, the type of pain was variable (one study was of neuropathic pain but not the other), and the time for measurement was not consistent.

Although studies suggest that ketamine may be a helpful adjuvant therapy to improve pain and decrease opioid requirements in patients with cancer, more studies are needed with larger sample sizes and control groups. Evidence is lacking to recommend ketamine in practice.