title: A randomized, double-blind, placebo-controlled pilot study of IV morphine-6-glucuronide for postoperative pain relief after knee replacement surgery.
abstract: OBJECTIVE
  To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain.
  
  
  METHODS
  Patients undergoing knee replacement surgery under spinal anesthesia were randomly assigned to 1 of 4 single intravenous M6G doses, 0 (placebo), 10, 20, or 30 mg/70 kg, administered 150 minutes after the spinal anesthetic was given. Analgesic effects were evaluated by determining the cumulative patient controlled analgesia (PCA) morphine dose, consumed over a 12 and 24 hours period, after the initial dose of M6G. For pain assessments, a 10 cm visual analog scale was used.
  
  
  RESULTS
  Data from 41 patients were evaluated (n=10, 10, 10, and 11 in the 0, 10, 20, and 30 mg M6G groups). Only at the highest M6G dose (30 mg/70 kg), morphine PCA consumption was significantly less compared with placebo: over the first 12 postoperative hours mean PCA morphine consumption was 3.0+/-2.0 mg/h after placebo and 1.4+/-0.5 mg/h after 30 mg M6G (P=0.03); over the first 24 h mean PCA morphine consumption was 2.5+/-2.1 mg after placebo and 1.0+/-0.4 mg after 30 mg M6G (P=0.04) (mean+/-SD). Visual analog scale values were similar across all groups during these time periods.
  
  
  CONCLUSIONS
  The analgesic effect of M6G in postoperative pain was demonstrated with 30 mg/70 kg M6G superior to placebo. At this dose, M6G has a long duration of action as determined by a reduction in the use of morphine PCA over 12 and 24 hours.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Raymonda
authors.initials: R
authors.lastname: Romberg
authors.forename: Eveline
authors.initials: E
authors.lastname: van Dorp
authors.forename: Justus
authors.initials: J
authors.lastname: Hollander
authors.forename: Michel
authors.initials: M
authors.lastname: Kruit
authors.forename: Alexander
authors.initials: A
authors.lastname: Binning
authors.forename: Terry
authors.initials: T
authors.lastname: Smith
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016058:Analgesia, Patient-Controlled / Q000379:methods; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000771:Anesthesia, Intravenous / Q000379:methods; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009022:Morphine Derivatives / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D010865:Pilot Projects; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide