Efficacy and safety of morphine-6-glucuronide (M6G) for postoperative pain relief: a randomized, double-blind study.
OBJECTIVE
The aim of the study was to assess analgesia and safety effects of a range of intravenous doses of M6G (10, 20 and 30 mg/70 kg), compared to placebo, in postoperative patients.


METHODS
In a randomized, multicentre, double-blind study, patients undergoing knee replacement surgery under spinal anaesthesia were administered one of three doses of M6G, or placebo, 150 min after spinal nerve block. Morphine rescue medication was available via a PCA pump. The key index of analgesic activity was determined as the amount of morphine consumed by the patient over 12 and 24 h after M6G administration. Time to first use of rescue medication, VAS and global pain assessment scales were also recorded. Safety was assessed by monitoring supine blood pressure, heart rate, respiratory rate and body temperature and typical opioid side-effects of PONV and sedation.


RESULTS
A total of 170 patients were dosed with study medication. M6G induced a dose-related reduction in morphine use over 24-h that reached statistical significance compared to placebo at M6G 30 mg/70 kg. There was no clear relationship between M6G dose and time to first use of PCA morphine. Pain relief was similar in all groups. M6G showed small, but inconsistent effects on the cardiovascular system and on sedation and no effects were observed on respiration or PONV.


CONCLUSIONS
M6G induced long-lasting dose-related analgesic effects in postoperative patients with limited effects on cardiorespiratory systems or of opioid-like side-effects. M6G is an effective opioid for the treatment of moderate to severe postoperative pain.
CeNeS Ltd, Cambridge, UK.
T W
TW
Smith
Alexander R
AR
Binning
Albert
A
Dahan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D001831:Body Temperature / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D009022:Morphine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects*; D010149:Postoperative Pain / Q000188:drug therapy*; D015990:Placebo Effect; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide