Both central sensitization after peripheral tissue injury and the development of opiate tolerance involve activation of N-methyl-D-aspartate receptors. In this double-blinded, randomized study, we investigated the preemptive versus postincisional effects of dextromethorphan, an N-methyl-D-aspartate receptor antagonist, on postoperative pain management. Sixty ASA I and II patients undergoing elective upper abdominal surgery were randomly allocated to three equally sized groups. The Preincisional group patients received dextromethorphan (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min before the end of surgery. The Postincisional group received the same dose of dextromethorphan 30 min before the end of surgery and a placebo 30 min before skin incision, and the Control group received a placebo both 30 min before skin incision and 30 min before the end of surgery. A standard general anesthetic technique including fentanyl, propofol, isoflurane, and atracurium was used. Postoperative meperidine patient-controlled analgesia (PCA) was used. There were no significant group differences in the median pain scores except in the visual analog scale at 6 h both at rest and on movement; these were significantly lower in the Preincisional group than the other two groups (P < 0.05). The mean time to initiation of PCA was significantly longer in the Preincisional than in the Postincisional and Control groups (mean [SD]: 10.7 [2.2 h], 5.4 [2.1 h], and 3.7 [1.6 h], respectively; P < 0.001]. The 24-h PCA-meperidine consumption was significantly less in the Preincisional than in the Postincisional and Control groups (mean [SD]: 140 [60 mg], 390 [80 mg], and 570 [70 mg], respectively; P < 0.001]. The incidence of postoperative hypoxemia (SpO(2) < 90%) and nausea was significantly less in the Preincisional group (P < 0.05). In conclusion, preincisional IM 120 mg dextromethorphan compared with the same postincisional dose significantly reduced postoperative meperidine consumption.
Implications: IM administration of preincisional dextromethorphan (120 mg), allowing the use of a larger dose sufficient to block the central sensitization caused by activation of the N-methyl-D-aspartate receptors, provides preemptive analgesia and has a supportive role in postoperative pain relief, as shown by a significant decrease in 24-h meperidine consumption.