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

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To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain.


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.


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.


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.

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