Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: A randomized, controlled, double-blind, crossover, double-dose study

Pain not responsive to morphine is often problematic Animal and clinical st udies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of k etamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pa in was unrelieved by morphine in a randomized, double-blind crossover; doub le-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomi ting drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not a t all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (TO) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minu tes (T180). Ketamine, but not saline solution, significantly reduced the pa in intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were repo rted in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg A significant difference in MMSE wets observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve m orphine analgesia in difficult pain syndromes, such as neuropathic pain. Ho wever, the occurrence of central adverse effects should be taken into accou nt, especially when using higher doses. This observation should be tested i n studies of prolonged ketamine administration. (C) U.S. Cancer Pain Relief Committee, 2000.