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PAIN MEDICINE

A Qualitative Systematic Review of the Role of N-Methyl-D-Aspartate Receptor Antagonists in Preventive Analgesia

Colin J. L. McCartney, FRCA^*, Avinash Sinha, FRCA^*, and Joel Katz, PhD^,,

*Department of Anesthesia and Pain Management, Toronto Western Hospital and University of Toronto; Department of Anesthesia, University of Toronto; Department of Anesthesia and Pain Management, Toronto General Hospital and Mount Sinai Hospital; and Department of Psychology and School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada

Address correspondence to Colin J. L. McCartney, MB ChB, FRCA, Department of Anesthesia and Pain Management, Toronto Western Hospital, EC2-046, 399 Bathurst St., Toronto M5T2S8, ON, Canada. Address e-mail to colin.mccartney{at}uhn.on.ca Reprints will not be available from the authors.

We evaluated in a qualitative systematic review the effect of N-methyl-D-aspartate (NMDA) receptor antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Randomized trials examining the use of an NMDA antagonist in the perioperative period were sought by using a MEDLINE (1966–2003) and EMBASE (1985–2003) search. Reference sections of relevant articles were reviewed, and additional articles were obtained if they evaluated postoperative analgesia after the administration of NMDA antagonists. The primary outcome was a reduction in pain, analgesic consumption, or both in a time period beyond five half-lives of the drug under examination. Secondary outcomes included time to first analgesic request and adverse effects. Forty articles met the inclusion criteria (24 ketamine, 12 dextromethorphan, and 4 magnesium). The evidence in favor of preventive analgesia was strongest in the case of dextromethorphan and ketamine, with 67% and 58%, respectively, of studies demonstrating a reduction in pain, analgesic consumption, or both beyond the clinical duration of action of the drug concerned. None of the four studies examining magnesium demonstrated preventive analgesia.

IMPLICATIONS: We evaluated, in a qualitative systematic review, the effect of N-methyl D-aspartate antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Dextromethorphan and ketamine were found to have significant immediate and preventive analgesic benefit in 67% and 58% of studies, respectively.

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