Wadhwa A, Clarke D, Goodchild C S, Young D
Monash University Department of Anaesthesia, Clayton, Victoria, Australia.
Anesth Analg. 2001 Feb;92(2):448-54. doi: 10.1097/00000539-200102000-00032.
Dextromethorphan is a weak N-methyl-d-aspartate (NMDA) receptor antagonist that inhibits spinal cord sensitization in animal models of pain and also inhibits the development of cutaneous secondary hyperalgesia after tissue trauma. Perhaps coadministration of an NMDA antagonist with an opioid would lead to better pain relief, particularly with movement and an opioid-sparing effect. This has been shown for ketamine, but previous studies with dextromethorphan that have used small doses have shown only a modest reduction in morphine requirements with no or minimal changes in the postoperative pain experience. We sought to determine whether a large dose of this drug, just below the maximum tolerated dose, could potentiate morphine analgesia while simultaneously causing a significant improvement in the management of the postoperative pain experience. Sixty-six patients undergoing knee surgery were enrolled in the study. The study design was a prospective, randomized double-blinded comparison with placebo of 200 mg of dextromethorphan given eight hourly. Postoperative pain experiences were assessed by postoperative morphine usage. Visual analog and verbal rating scales were used to assess pain with movement as well as side effects. Dextromethorphan treatment led to a significant but modest reduction in morphine requirements (29.3% P < 0.05) but no reduction in postoperative pain levels. We conclude that increasing orally administered dextromethorphan to near maximum tolerated doses does not provide greater morphine sparing than 20-40 mg given 6-8 hourly as in previous studies. Furthermore we conclude that dextromethorphan does not improve pain scores in a manner expected of a drug with NMDA antagonist properties.
右美沙芬是一种弱效N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在动物疼痛模型中可抑制脊髓致敏，还能抑制组织创伤后皮肤继发性痛觉过敏的发展。或许将NMDA拮抗剂与阿片类药物联合使用能更好地缓解疼痛，尤其是在活动时，并具有阿片类药物节省效应。氯胺酮已证实有此效果，但之前使用小剂量右美沙芬的研究仅显示吗啡需求量有适度减少，术后疼痛体验无变化或仅有极小变化。我们试图确定，在略低于最大耐受剂量的情况下，大剂量使用该药物是否能增强吗啡镇痛效果，同时显著改善术后疼痛体验的管理。66名接受膝关节手术的患者参与了该研究。研究设计为前瞻性、随机双盲对照试验，将每8小时服用200毫克右美沙芬与安慰剂进行比较。通过术后吗啡用量评估术后疼痛体验。使用视觉模拟评分法和语言评定量表评估活动时的疼痛及副作用。右美沙芬治疗使吗啡需求量显著但适度减少（29.3%，P<0.05），但术后疼痛水平未降低。我们得出结论，与之前的研究一样，将口服右美沙芬剂量增加至接近最大耐受剂量，并不会比每6 - 8小时服用20 - 40毫克更能节省吗啡。此外，我们得出结论，右美沙芬并不能像具有NMDA拮抗剂特性的药物那样改善疼痛评分。
