A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia.
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.


CONCLUSIONS
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.
McCartney
Colin J L
CJ
Department of Anesthesia and Pain Management, Toronto Western Hospital and University of Toronto, Ontario, Canada. colin.mccartney@uhn.on.ca
Sinha
Avinash
A
Katz
Joel
J
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003915:Dextromethorphan / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use; D016239:MEDLINE; D008274:Magnesium / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012107:Research Design
D000701:Analgesics, Opioid; D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003915:Dextromethorphan; D008274:Magnesium