Contemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less postdischarge 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 IV 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 30-day opioid consumption, pain, opioid side effects, and leftover opioid counts.


Median (interquartile range) intraoperative methadone doses were 6 (5 to 7), 11 (10 to 12), 14 (13 to 16), and 18 (15 to 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 (IV milligram morphine equivalents [MME]) was 25 (20 to 37), 20 (13 to 30), 27 (18 to 32), and 25 (20 to 36) mg, respectively, in patients receiving 0.1, 0.2, 0.25 and 0.3 mg/kg methadone, compared to 46 (33 to 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.

Editor’s Perspective
What We Already Know about This Topic
  • Opioids are the mainstay and most efficacious systemic pharmacotherapy for treating moderate to severe intraoperative and postoperative pain, but they have side effects
  • Methadone is a highly effective and opioid-sparing perioperative opioid
  • Compared with shorter-acting opioids, intraoperative methadone has been reported to decrease not only postoperative pain and opioid use but also chronic pain and opioid use after surgery
What This Article Tells Us That Is New
  • A randomized, double-blind, dose-escalation study was conducted to determine the feasibility of single-dose intraoperative methadone for next-day discharge outpatient surgery, identify an optimally analgesic and well-tolerated dose, and explore whether it would result in less postoperative opioid use than shorter-acting opioids
  • Anesthesia with single-dose methadone was both feasible and effective for next-day discharge outpatient surgery
  • The intraoperative methadone dose that best combined opioid sparing, analgesia, minimal adverse events, and advantages compared with shorter-acting opioids was 0.25 mg/kg ideal body weight (median, 14 mg)