title: Preemptive intravenous morphine-6-glucuronide is ineffective for postoperative pain relief.
abstract: BACKGROUND
  Morphine-6-glucuronide (M-6-G), a major metabolite of morphine, is reported to be more potent than morphine when administered intrathecally; however, its efficiency remains under debate when administered intravenously. This study was designed to assess the analgesic efficiency of intravenous M-6-G for the treatment of acute postoperative pain.
  
  
  METHODS
  After informed consent was obtained, 37 adults (American Society of Anesthesiologists physical status I-II) who were scheduled for elective open knee surgery were enrolled in the study. General anesthesia was induced with thiopental, alfentanil, and vecuronium and was maintained with a mixture of nitrous oxide/isoflurane and bolus doses of alfentanil. At skin closure, patients were randomized into three groups: (1) morphine group (n = 13), which received morphine 0.15 mg/kg; (2) M-6-G group (n = 12), which received M-6-G 0.1 mg/kg; and (3) placebo group (n = 12), which received saline. At the time of extubation, plasma concentration of morphine and M-6-G was measured. Postoperative analgesic efficiency was assessed by the cumulative dose of morphine delivered by patient-controlled analgesia. Opioid-related side effects were also evaluated.
  
  
  RESULTS
  No difference was noted in patient characteristics and opioid-related side effects. Morphine requirements (mean +/- SD) during the first 24 h in the M-6-G group (41+/-9 mg) and the placebo group (49+/-8 mg) were significantly greater (P<0.05) compared with the morphine group (29+/-8 mg).
  
  
  CONCLUSIONS
  A single intravenous bolus dose of M-6-G was found to be ineffective in the treatment of acute postoperative pain. This might be related to the low permeability of the blood-brain barrier for M-6-G.
authors.affiliation: Department of Anesthesia, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (ap-hp), Creteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Motamed
authors.forename: X
authors.initials: X
authors.lastname: Mazoit
authors.forename: K
authors.initials: K
authors.lastname: Ghanouchi
authors.forename: F
authors.initials: F
authors.lastname: Guirimand
authors.forename: K
authors.initials: K
authors.lastname: Abhay
authors.forename: T
authors.initials: T
authors.lastname: Lieutaud
authors.forename: S
authors.initials: S
authors.lastname: Bensaid
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.forename: P
authors.initials: P
authors.lastname: Duvaldestin
mesh_terms: D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007717:Knee / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide