Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1.

CONSORT diagram

Figure 2:

Postoperative opioid use after intraoperative anesthesia with short-duration or long-duration opioids. All opioid administration is quantified as mg IV morphine equivalents (median and 25^th and 75% quartiles). (A) Total opioid use in the post-anesthesia recovery unit (PACU). (B) Total opioid use on the day of surgery after PACU discharge (C) Total opioid use in the PACU and post-PACU on the day of surgery. (D) Total opioid use in the hospital on postoperative day 1. (E) Total opioid use during the entire hospital stay. Exploratory statistical analysis found total hospital opioid use in all methadone groups significantly different from controls (short duration opioid) (P<0.001).

Figure 3:

Postoperative alertness and sedation. Modified Observer’s Alertness and Sedation Score range is from unresponsive (0) to responding to spoken name (5). Results are the median and 25^th and 75% quartiles in each group.

Figure 4:

Pain after surgery. Subjects rated their pain using a 100 mm visual scale. Results are the median and 25^th and 75% quartiles. Data were not available for the patients receiving 0.3 mg/kg methadone.

Figure 5:

Home opioid use after hospital discharge. Opioid use was quantified for 30d postoperatively. Results are the median and 25^th and 75% quartiles. (A)Opioid consumption in mg IV morphine equivalents. (B) Fraction of the number of pills used compared to the number prescribed, calculated as the median of individual patient results.

Figure 6:

Pain after surgery. Subjects rated their pain daily using a 100 mm visual scale. Results are the sum of 30d pain scores for each patient, presented as median and 25^th and 75% quartiles. Data were not available for the patients receiving 0.3 mg/kg methadone.

Figure 7:

Pain interference after surgery. Participants were queried once weekly for 4 weeks postoperatively for their response to questions of A) It was hard for me to walk one block when I had pain, B) I had trouble sleeping when I had pain, C) It was hard for me to run when I had pain, and D) It was hard for me to pay attention when I had pain, using a 5 point scale (never=0, almost never=1, sometimes=2, often=3, almost always=4). Data are shown for day 7. Results are the median and 25^th and 75% quartiles. Medians were zero for most responses after day 7.

Figure 8:

Opioid-related side effects. Effects were measured using the opioid-related symptom distress scale (ORSDS). Results are the median and 25^th and 75% quartiles.