Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients: a randomized, placebo-controlled, double-blind study.
BACKGROUND
Postoperative pain is mediated centrally by N-methyl-D-aspartate (NMDA) receptors. The beneficial effects of preincision oral dextromethorphan (DM), which is an NMDA antagonist, on postoperative pain and intravenous patient-controlled analgesia (IV-PCA) morphine (MO) consumption have been examined in patients undergoing surgery. The authors investigated 75 patients who underwent surgery for bone and soft tissue malignancies, in whom postoperative pain is more severe compared with patients who undergo general surgery.


METHODS
Patients received placebo, DM 60 mg, or DM 90 mg (25 patients per group) before surgery and on each of the two following days in a randomized, double-blind, placebo-controlled manner. Postoperative IV-PCA MO was started when subjective pain intensity was >/= 4/10 (visual score) and lasted for 72 hours. Rescue drugs on demand were oral paracetamol or dipyrone.


RESULTS
The patients in the DM60 and DM90 groups similarly experienced 50-80% less pain (P < 0.01) compared with patients in the placebo group, both immediately and up to 3 days postoperatively, as well as a 50% reduction in the estimated overall maximal pain intensity (P < 0.01). Both DM groups consumed 50-70% less MO than the nonmedicated individuals in the placebo group (P < 0.01), and their demand for rescue drugs on the first postoperative day also was significantly lower (P < 0.01). Patients in the DM groups also were sedated less ( approximately 70%; P < 0.01). There were no differences among the groups in terms of when the patients left their beds, when they were discharged home, or the number of overall side effects.


CONCLUSIONS
DM is associated with reduced pain intensity, sedation, and analgesic requirements, even in patients undergoing surgery for bone and soft tissue malignancies. A 3-day DM administration neither increased the incidence of side effects nor accelerated ambulation and discharge home.
Weinbroum
Avi A
AA
Postanesthesia Care Unit, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Israel. draviw@tasmc.health.gov.il
Gorodetzky
Alexander
A
Nirkin
Alexander
A
Kollender
Yehuda
Y
Bickels
Jacob
J
Marouani
Nissim
N
Rudick
Valery
V
Meller
Isaac
I
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000601:surgery*; D003915:Dextromethorphan / Q000494:pharmacology*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D019637:Orthopedic Procedures / Q000009:adverse effects*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D010351:Patient Discharge; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012646:Self Administration; D012983:Soft Tissue Neoplasms / Q000601:surgery*; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D009020:Morphine