Co-administration of dextromethorphan and morphine: reduction of post-operative pain and lack of influence on morphine metabolism

Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):680-4. doi: 10.1111/j.1742-7843.2010.00559.x. Epub 2010 Mar 22.

Abstract

We investigated co-analgesic effect of dextromethorphan in adolescent post-operative patients with idiopathic scoliosis. In a double-blind study, 60 patients with ASA physical status I-II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 +/- 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. Group placebo (n = 30; age: 16.5 +/- 2.7 years) received placebo at identical times. Post-operative analgesic requirements were assessed using nurse-controlled analgesia system. Pain was assessed using numeric rating scale before first administration of morphine and at 2, 3, 4, 6, 24 and 48 hr after operation. Blood samples were taken 20 min. after the first use of morphine (within 1 hr after operation). The total use of analgesics during surgery was lower in the dextromethorphan group. The dose of morphine providing relief immediately after surgery, as well as total analgesic requirements in the first and second day after surgery did not differ between groups. Subjectively evaluated pain intensity score (numeric rating scale) was lower for the dextromethorphan patients in the first 4 hr, but not later after surgery. Plasma levels of morphine, morphine-6-glucuronide and morphine-3-glucuronide did not differ between groups. Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post-operative period. In such patients, co-analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / pharmacokinetics
  • Dextromethorphan / administration & dosage*
  • Dextromethorphan / pharmacokinetics
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Morphine / administration & dosage*
  • Morphine / metabolism
  • Morphine / pharmacokinetics
  • Nurse's Role
  • Pain / prevention & control
  • Pain Measurement
  • Pain, Postoperative / metabolism
  • Pain, Postoperative / prevention & control*
  • Scoliosis / metabolism
  • Scoliosis / surgery
  • Spine / surgery

Substances

  • Analgesics, Opioid
  • Dextromethorphan
  • Morphine