A Comparison of Intrathecal Morphine-6-Glucuronide and Intrathecal Morphine Sulfate as Analgesics for Total Hip Replacement

Abstract

Postoperative analgesia was assessed after intrathecal administration of morphine-6-glucuronide (M6G) 100 micrograms and 125 micrograms in 75 patients undergoing total hip replacement. Analgesia was excellent and was similar to that obtained after intrathecal administration of morphine sulfate 500 micrograms. Visual analog pain scores recorded postoperatively were low (median = 0) and were similar in all three groups. However, at 6 and 10 h after operation significantly more patients in the M6G 125 group recorded pain as 0 compared with patients in the morphine group (P < 0.04, P < 0.01) and significantly more patients in the M6G 100 group recorded pain as 0 at 24 h after operation compared with patients in the morphine group (P < 0.04). Postoperative meperidine consumption using a patient-controlled system was also similar in each of the three treatment groups. Nausea and emesis occurred frequently in all groups; morphine (nausea 88%, vomiting 76%), M6G 100 micrograms (nausea 76%, vomiting 64%), and M6G 125 micrograms (nausea 88%, vomiting 60%). Respiratory depression occurred in two and three patients, respectively, in the M6G 100-microgram and 125-microgram groups but did not occur in any patient who received morphine sulfate. The lack of statistical significance in the difference in incidence of respiratory depression between the groups may represent a type II error. However, the risk of late respiratory depression developing after administration of any intrathecal opioid necessitates careful postoperative observation of patients. As M6G is a potent intrathecal analgesic further investigation of this drug using small doses may be useful.

Improved Brain Uptake and Pharmacological Activity Profile of Morphine-6-Glucuronide Using a Peptide Vector-Mediated Strategy

“…In one study in humans, M6G was shown to produce fewer respiratory effects than morphine (Peat et al, 1991;Thompson et al, 1995). However, this study was not compatible with the other observations where respiratory depression was observed after intrathecal administration of M6G in human subjects (Grace and Fee, 1996). In the present study, rats that received a high dose of M6G exhibited a significant increase in the pCO 2 .…”

“…M6G is thought to contribute to the pharmacological effects of the parent drug (Abbott and Palmour, 1988;Paul et al, 1989;Frances et al, 1992), and various clinical trials have used M6G as the therapeutic drug in preference to morphine (Hanna et al, 1990;Thompson et al, 1995;Grace and Fee, 1996;Lötsch et al, 1997;Motamed et al, 2000;Penson et al, 2000). Antinociception studies in experimental animals have demonstrated that, although M6G and morphine are almost equally potent after systemic administration, the analgesic potency of M6G is more than 100-fold higher than morphine after intracerebroventricular injection, a route of administration that bypasses the bloodbrain barrier (BBB) in vivo (Abbott and Palmour, 1988;Paul et al, 1989;Frances et al, 1992).…”

Définitions de la “dépression respiratoire” de l’analgésie postopératoire réalisée avec de la morphine intrathécale : une revue documentaire

“…17 There also exist less common definitions of RD. These include statistical analyses of respiratory variables, 10 RR with LOS, 26,59 and specific radiographic and/or laboratory abnormalities. 61 Johnson et al defined RD with multiple criteria, including RR, PaCO 2 , drowsiness, naloxone treatment and respiratory failure.…”

“…20 Quite commonly, there was no definition whatsoever, despite the use of this term. 21,22 Definitions of RD in postoperative ITM analgesia literature included: a low respiratory rate (RR), 23 high arterial PCO 2 values, 24 low oxyhemoglobin saturation with pulse oximetry (SpO 2 ), 25 increased level of sedation (LOS), 26 depressed ventilatory response to hypoxia and hypercarbia, 27 the need for naloxone treatment, 7 or a combination of these. However, the lack of a more specific or uniform definition of RD makes it difficult to ascertain its true incidence.…”

Safety of opioid patch initiation in Australian residential aged care

“…naloxone, and a high incidence of nausea (76% to 88%, depending on dose) and vomiting (60% to 64%) (Grace & Fee, 1996 Level II).…”