title: The median effective dose of tramadol and morphine for postoperative patients: a study of interactions.
abstract: Tramadol is a centrally-acting analgesic drug. In a search of an effective balanced analgesia technique with a morphine-sparing component, we studied the median effective analgesic doses (ED(50)) of tramadol, morphine, and their combination to determine the nature of their interaction using an isobolographic analysis. In this double-blind, randomized, two-stage prospective study, 90 postoperative patients were enrolled in one of three groups. The dose of tramadol and morphine received by a particular patient was determined using an up-down allocation technique. Initial doses and increments were, respectively, 100 mg and 10 mg in the tramadol group and 5 mg and 1 mg in the morphine group. In the second part, a 40:3 tramadol:morphine dosing ratio was used. The threshold of effective analgesia was defined as 3 or less on a numerical pain score (0-10). Isobolographic analysis was subsequently applied. The ED(50) values (95% confidence interval) of tramadol and morphine were, respectively, 86 mg (57-115 mg) and 5.7 mg (4.2-7.2 mg). The ED(50) of the combination was 72 mg (62-82 mg) for tramadol and 5.4 mg (4-6.6.2 mg) for morphine. The combination of tramadol and morphine was infra-additive and thus not recommended for postoperative analgesia.
authors.affiliation: Department of Anesthesiology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, F-94275 Le Kremlin-Bicêtre and Anesthesia Laboratory UPRES EA 3540, Faculté de Médecine du Kremlin-Bicêtre, Université de Paris-Sud, F-94276 Le Kremlin-Bicêtre, France.
authors.forename: Thi Aurore
authors.initials: TA
authors.lastname: Marcou
authors.forename: Sophie
authors.initials: S
authors.lastname: Marque
authors.forename: Jean-Xavier
authors.initials: JX
authors.lastname: Mazoit
authors.forename: Dan
authors.initials: D
authors.lastname: Benhamou
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000188:drug therapy*; D011446:Prospective Studies; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol; D009020:Morphine