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

In Brief 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. IMPLICATIONS: The pharmacologic interaction between tramadol and morphine was studied in the postoperative period. Their potency ratio was 10:3 (morphine:tramadol) and the combination showed infra-additivity. We do not recommend the combination of morphine and tramadol for postoperative analgesia.