Contemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less post-discharge opioid prescribing. For inpatient surgery, anesthesia with intraoperative methadone, compared with short-duration opioids, results in less pain, less postoperative opioid use, and greater patient satisfaction. This pilot investigation aimed to determine single-dose intraoperative methadone feasibility for next-day discharge outpatient surgery, determine an optimally analgesic and well-tolerated dose, and explore whether methadone would result in less postoperative opioid use compared with conventional short-duration opioids.


This double-blind, randomized, dose-escalation feasibility and pilot study in next-day discharge surgery compared intraoperative single-dose intravenous methadone (0.1 then 0.2, 0.25 and 0.3 mg/kg ideal body weight) versus as-needed short-duration opioid (fentanyl, hydromorphone) controls. Perioperative opioid use, pain, and side effects were assessed before discharge. Patients recorded pain, opioid use, and side effects for 30 days postoperatively using take-home diaries. Primary clinical outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30d opioid consumption, pain, opioid side effects, and left-over opioid counts.


Median (IQR) intraoperative methadone doses were 6 (5-7), 11 (10-12), 14 (13-16), and 18 (15-19) mg in 0.1, 0.2, 0.25, and 0.3 mg/kg ideal body weight groups, respectively. Anesthesia with single-dose methadone and propofol or volatile anesthetic was effective. Total in-hospital opioid use (mg IV morphine equivalents) was 25 (20-37), 20 (13-30), 27 (18-32), and 25 (20-36) mg, respectively, in patients receiving 0.1, 0.2, 0.25 and 0.3 mg/kg methadone, compared to 46 (33-59) mg in short-duration opioid controls. Opioid-related side effects were not numerically different. Home pain and opioid use were numerically lower in patients receiving methadone.


The most effective and well-tolerated single intraoperative induction dose of methadone for next-day discharge surgery was 0.25 mg/kg ideal body weight (median 14 mg). Single-dose intraoperative methadone was analgesic and opioid-sparing in next-day discharge outpatient surgery.