Plasma concentrations of methadone during postoperative patient-controlled extradural analgesia

Plasma concentrations of methadone were measured by gas chromatography in 16 patients receiving extradural methadone by continuous infusion for relief of postoperative pain. Venous blood samples were taken after a loading dose of extradural methadone 2 mg and during infusion of 0.46 mg h-1 plus patient-controlled increments of 0.2-1 mg. Mean (SD) plasma concentration of methadone was 9.8 (2.1) ng ml-1 at 15 min; this did not change significantly during the first 2 h, after which it increased gradually to 32.2 (4.6) ng ml-1 (P less than 0.001) at the end of 24 h. The mean quantity of extradural methadone required to produce effective analgesia was 10.3 (1.8) mg during the first 12 h after operation and 6 (1.0) mg for the subsequent 12 h. The mean amount of methadone for effective analgesia on the second day was 7.6 (1.1) mg. No adverse effects were detected during the 2-3 days of methadone therapy. Plasma concentration of methadone increased significantly during patient-controlled infusion of extradural methadone in the first 24 h after operation, suggesting rapid vascular uptake. Systemic activity of the drug contributes to the analgesic effect of extradural methadone.