Background and Objectives. The efficacy of methadone administered by continuous epidural infusion for 24 hours for the management of postoperative pain has been reported. The pharmacokinetic characteristics of methadone predict that significant accumulation would occur if infusions were continued for longer than 24 hours and that this accumulation could result in serum concentrations above the threshold associated with systemic analgesia.

Methods. We tested this hypothesis by measuring serum methadone concentrations, pain scores, and side effects in 18 patients receiving continuous epidural infusions of methadone for the relief of postoperative pain after lower abdominal surgery over 3 days.

Results. Twelve of 18 patients completed the study. Persistent inadequate analgesia required a change in the infusion mixture in 5 of these patients by the second postoperative day. The sixth patient suffered a fatal pulmonary embolus (judged to be unrelated to the study) on the morning of the first postoperative day. Methadone concentrations increased significantly from 20 ± 18 ng/ml (median ± quartile) on postoperative Day 1 to 70 ± 47 ng/ml on Day 3. Pain relief scores steadily increased from 50 ± 5 at 2 hours postoperatively to 83 ± 5 by Day 3. The only side effects noted in the present study were nausea and sedation.

Conclusion. The accumulation of serum concentrations reported here argue that the risks of thoracic epidural placement may out-weigh the potential benefits when methadone is administered alone by continuous infusion for longer than 24 hours.