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A Randomized, Double-blind, Placebo-controlled Pilot Study of IV Morphine-6-Glucuronide for Postoperative Pain Relief After Knee Replacement Surgery

Romberg, Raymonda MD, PhD*; van Dorp, Eveline MD*; Hollander, Justus MSc; Kruit, Michel MD; Binning, Alexander MD; Smith, Terry PhD§; Dahan, Albert MD, PhD*

doi: 10.1097/AJP.0b013e31802b4f6a
Original Articles

Objectives 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.

Discussion 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.

*Department of Anesthesiology, Leiden University Medical Center, 2300 RC Leiden

Rijnland Hospital, 2353 GA Leiderdorp, The Netherlands

Department of Anaesthetics, Gartnavel General Hospital, Glasgow G12 0YN

§CeNeS Ltd, Cambridge CB4 9ZR, UK

Supported in part by CeNeS Ltd, Cambridge, UK.

Reprints: Prof Dr Albert Dahan, Department of Anesthesiology, Leiden University Medical Center (LUMC), P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands (e-mail:

Received for publication May 15, 2006; accepted October 8, 2006

© 2007 Lippincott Williams & Wilkins, Inc.