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Failure of Proglumide, a Cholecystokinin Antagonist, to Potentiate Clinical Morphine Analgesia

A Randomized Double-Blind Postoperative Study Using Patient-Controlled Analgesia (PCA)

Received from the Department of Anesthesiology, University of Cologne, Federal Republic of Germany.

Abstract

The potential clinical utility of drug interactions between morphine and the cholecystokinin antagonist proglumide was examined in 80 postoperative patients suffering from moderate to severe pain. Four groups of ASA I-III patients (mean age 51 years, mean weight 72 kg) recovering from major abdominal or gynecological surgery (mean duration of surgery 141 minutes) performed under balanced anesthesia (midazolam, droperidol, fentanyl, N₂O, enflurane) were randomly assigned to self-administer morphine-proglumide mixtures on the first postoperative day (ODAC; morphine demand dose 3 mg; infusion rate 0.36 mg/hr; lockout time 2 minutes; hourly maximum dose 15 mg/hr; proglumide doses per demand 0, 50 µg, 100 µg, or 50 mg). Morphine consumption, actual as well as retrospective pain scores (0–5) and side effects were evaluated. Mean duration of patient-controlled analgesia (PCA) in the subgroups was 17–19 hours, during which time 24.6 ± 9.5 to 28.0 ± 3.4 µg morphine·kg^–1·hr^–1 was given. There were no statistically significant differences between the groups either for drug consumption, pain scores, or side effects. It is therefore concluded that proglumide does not potentiate morphine analgesia in a clinical (postoperative) setting.

Key Words: ANALGESICS—morphine • DRUG INTERACTIONS—cholecystokinin, proglumide • PAIN, POSTOPERATIVE—patient-controlled analgesia