Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery

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.