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PAIN MEDICINE

The Median Effective Dose of Tramadol and Morphine for Postoperative Patients: A Study of Interactions

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

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 (ED₅₀) 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 ED₅₀ 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 ED₅₀ 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.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999