Intrathecal ketamine reduces morphine requirements in patients with terminal cancer pain

Purpose: Ketamine has been administered epidurally and intrathecally for operative and post-operative pain control. Animal studies showed potentiation of analgesia induced by ketamine and morphine. We hypothesized that intrathecal ketamine would potentiate the effects of intrathecal morphine in the treatment of cancer pain. Methods: A double blind, cross over study was designed to evaluate the effect of ketamine on spinal morphine analgesia in terminal cancer pain patients. A two-phase protocol was used; phase M, intrathecal morphine alone twice daily; phase M+K, co-administration of ketamine (1.0 mg) with morphine intrathecally twice daily. The dose of morphine was titrated upwards until acceptable pain relief was achieved, defined by numeric rating scales (0-10) ≤3, and the rescue dose of morphine was less than 5 mg after each intrathecal administration for two days. The dose of intrathecal morphine was defined as the effective dose. Results: The effective dose of intrathecal morphine in phase M of 0.38 ± 0.04 mg · day^-1 was higher than that in phase M+K (0.17 ± 0.02 mg · day^-1) (P < 0.05). The average pain scales were 7.95 ± 0.25 before intrathecal drug administration. Pain scales were decreased to 2.2 ± 0.17 (P < 0.05) in phase M and 1.95 ± 0.20 (P < 0.05) in phase M+K after the effective dose of morphine had been reached. No serious side effects were observed in this study. Conclusion: The present study demonstrates that ketamine enhances the analgesic effect of morphine, thus reducing the dose of intrathecal morphine.