Randomized, double-blind study of the analgesic efficacy of morphine-6-glucuronide versus morphine sulfate for postoperative pain in major surgery

Anesthesiology. 2005 Apr;102(4):815-21. doi: 10.1097/00000542-200504000-00018.


Background: Morphine-6-glucuronide (M6G) has promising preclinical characteristics and encouraging pharmacokinetic features for acute nociceptive pain. Early studies have produced a good safety profile when compared to morphine sulfate, although in surrogate pain models studies, a mixed picture emerged. A study to evaluate the efficacy and safety profile in a clinical setting was designed.

Methods: The authors conducted a double-blind, randomized, dose-finding study of patients scheduled to undergo major joint replacement. One hundred patients of both sexes were included, with 50 patients in each group. A loading dose of 10 mg of study medication was given intravenously at induction of anesthesia, and two further doses were allowed during surgery if required. Bolus doses via a patient-controlled analgesia system were given subcutaneously at 2 mg/dose and set at a 10-min lockout. Assessments of pain intensity and relief were recorded during the 24-h period.

Results: There were no statistically significant differences between the treatments for 24-h mean pain intensity. However, pain intensity was significantly higher in the M6G group than in the morphine group at 30 min and 1 h. There was no statistical difference in 24-h mean pain relief or retrospective pain scores at any time point during the 24-h period. The severity of sedation was significantly greater in the morphine group than in the M6G group at 30 min, 1 h, 2 h, and 24 h. Respiratory depression was greater in the morphine group than in the M6G group, and more patients in the morphine group withdrew from the study because of respiratory depression.

Conclusions: Overall, M6G has an analgesic effect similar to that of morphine over the first 24 h postoperatively. However, M6G may be slower onset initially than morphine; therefore, a larger initial dose may be required.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesia, Patient-Controlled
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Morphine Derivatives / adverse effects
  • Morphine Derivatives / therapeutic use*
  • Pain Measurement / drug effects
  • Pain, Postoperative / drug therapy*
  • Postoperative Nausea and Vomiting / chemically induced
  • Postoperative Nausea and Vomiting / epidemiology
  • Substance Withdrawal Syndrome / psychology


  • Analgesics, Opioid
  • Morphine Derivatives
  • morphine-6-glucuronide
  • Morphine