The effect of ketamine as adjuvant to opioid for intractable cancer pain

Background : There has been growing evidence of the importance of the N-methyl-D- aspartate (NMDA) receptor in intractable pain. There is good evidence from experimental animal models and clinical trials that ketamine as a NMDA receptor antagonist relieves neuropathic pain. We evaluated whether ketamine in low doses as an adjuvant to opioid treatment improves analgesia with tolerable adverse effects. Methods : 58 patients with intractable cancer pain received ketamine for 3 days. Each pain type was classified as a somatic, visceral, or neuropathic pain. We assessed pain at 6 hourly intervals with vital signs using a numeric rating scale. Data on opioid doses, ketamine dose, and adverse effects were recorded daily on an assessment chart. To be designated as a responder, a patient had to show a 50% or greater reduction in the mean pain scale. Results : The overall response rate was 34.5%. The results according to the type of pain mechanism showed that 47% (15/32) patients with neuropathic and 25% (5/20) patients with somatic pain responded. In 24 cases (41.4%), the requirement for an opioid dose was reduced after infusion of ketamine. The most common adverse effects were nausea and vomiting. Eleven patients complained of drowsiness or transient hallucination. However, most adverse effects were mild to moderate and were easily relieved by treatment. Conclusions : This study demonstrates that the infusion of ketamine in low doses may have an effect on intractable cancer pain and in reducing opioid requirements, especially neuropathic pain with acceptable toxicities. Therefore, ketamine may be useful as an adjuvant to opioid treatment in cancer patients who are receiving palliative care.