Epidural morphine plus ketamine for upper abdominal surgery: improved analgesia from preincisional versus postincisional administration.

Increased postoperative pain may be caused by central nervous system plasticity, which may be related to actions of N-methyl-D-aspartic acid (NMDA) receptors on neurons in the dorsal horn of the spinal cord. Opioids act mainly on presynaptic receptors and reduce neurotransmitter release, while ketamine antagonizes NMDA receptors and prevents wind-up and long-term potentiation. Thus, we postulated that central nervous system sensitization would be prevented more effectively by the preoperative use of these two drugs simultaneously, and the effect of preemptive analgesia would be demonstrated. Ketamine, 60 mg, and morphine, 2 mg, were injected epidurally through an indwelling catheter that was inserted at the T7-8 interspace in 60 ASA physical status class 1-2 patients. The drugs were injected before induction of anesthesia (Group 1; n = 30) or immediately after removal of a surgical specimen (Group 2; n = 30). An additional 2 mg of morphine was injected when the patients complained of resting pain. The analgesic effect was assessed by the time from first analgesic injection to second dose and the number of patients who needed supplemental injections. Complications were also noted. The duration of analgesia was longer (P < 0.01) in Group 1 (31.1 +/- 16.0 h) than in Group 2 (21.1 +/- 12.0 h), and the proportion of patients who needed supplemental injections was decreased (P < 0.05) in Group 1 (56.7%) compared with Group 2 (90.0%). The incidence of adverse effects was not different between the two groups. In conclusion, preoperative administration of morphine and ketamine is more effective in reducing postoperative pain than it is when given during the operation.