Ilkjaer S, Bach L F, Nielsen P A, Wernberg M, Dahl J B
Department of Anaesthesiology, Skejby Hospital, Aarhus University Hospital, DK-8200, Aarhus, Denmark.
Pain. 2000 May;86(1-2):19-24. doi: 10.1016/s0304-3959(99)00305-x.
Dextromethorphan is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that NMDA-receptor antagonists may potentiate the effect of analgesics such as morphine, local anesthetics and NSAIDs. Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting, possibly related to administration of insufficient doses of the drug. Fifty patients scheduled for non-malignant elective abdominal hysterectomy in general anesthesia were randomized to receive oral dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received patient-controlled analgesia with morphine for 24 h postoperatively as the only analgesic. Patient-controlled analgesia (PCA) morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during cough, or during mobilization, pressure pain detection thresholds, von Frey hair pain detection thresholds, or peak flow. At 24 h after operation, hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption (Rs=0.28, P=0.05). Three months postoperatively, hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (nausea, vomiting, sedation). In conclusion, oral dextromethorphan 150 mg reduced PCA morphine consumption immediately (0-4 h) after hysterectomy, without prolonged effects on pain or wound hyperalgesia. A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption was demonstrated.
右美沙芬是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已知其可抑制脊髓背角神经元的wind-up及NMDA介导的伤害性反应。实验和临床研究表明，NMDA受体拮抗剂可能会增强镇痛药（如吗啡、局部麻醉药和非甾体抗炎药）的效果。先前右美沙芬用于术后疼痛的临床研究结果相互矛盾，这可能与药物剂量不足有关。五十例计划在全身麻醉下进行非恶性择期腹部子宫切除术的患者被随机分为两组，一组在手术前1小时口服150毫克右美沙芬，另一组口服安慰剂。患者术后24小时接受吗啡自控镇痛，作为唯一的镇痛方式。与安慰剂组相比，接受右美沙芬治疗的患者术后0至4小时吗啡自控镇痛（PCA）的用量减少了30%（P=0.02）；术后5至24小时未观察到差异。两组在静息、咳嗽或活动时的视觉模拟量表评分、压痛检测阈值、von Frey毛发痛觉检测阈值或峰值流量方面均无显著差异。术后24小时，25例接受右美沙芬治疗的患者中有23例、25例接受安慰剂治疗的患者中有22例在手术伤口近端对von Frey毛发刺激出现痛觉过敏，两组之间无显著差异。两组的汇总数据显示，术后24小时痛觉过敏程度与术后24小时PCA吗啡总用量之间存在微弱但显著的相关性（Rs=0.28，P=0.05）。术后三个月，右美沙芬组22例接受检查的患者中有18例、安慰剂组23例患者中有16例仍可检测到痛觉过敏，两组之间无统计学差异。副作用（恶心、呕吐、镇静）方面无显著差异。总之，口服150毫克右美沙芬可在子宫切除术后立即（0至4小时）减少PCA吗啡用量，对疼痛或伤口痛觉过敏无长期影响。研究证实了术后24小时伤口痛觉过敏程度与术后24小时PCA吗啡总用量之间存在正相关。
