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Intraoperative Methadone in Same-Day Ambulatory Surgery

A Randomized, Double-Blinded, Dose-Finding Pilot Study

Komen, Helga, MD*; Brunt, L. Michael, MD; Deych, Elena, MS; Blood, Jane, RN*; Kharasch, Evan D., MD, PhD*,§,‖

doi: 10.1213/ANE.0000000000003464
Chronic Pain Medicine: Original Clinical Research Report

BACKGROUND: Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery.

METHODS: A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects.

RESULTS: Median (interquartile range) methadone doses were 6 (5–6) and 9 (8–9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3–11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1–3.3; P < .001) but not 0.1 mg/kg methadone (5.0 mg, 3.3–8.1; P = .60). Dose-escalation ended at 0.15 mg/kg methadone. Total in-hospital nonmethadone opioid use after short-duration opioid, 0.1 mg/kg methadone, and 0.15 mg/kg methadone was 35.3 (25.0–44.0), 7.1 (3.7–10.0), and 3.3 (0.1–5.8) mg morphine equivalents, respectively (P < .001 for both versus control). In-hospital pain scores and side effects were not different between groups. In the 30 days after discharge, patients who received methadone 0.15 mg/kg had less pain at rest (P = .02) and used fewer opioid pills than controls (P < .0001), whereas patients who received 0.1 mg/kg had no difference in pain at rest (P = .69) and opioid use compared to controls (P = .08).

CONCLUSIONS: In same-day discharge surgery, this pilot study identified a single intraoperative dose of methadone (0.15 mg/kg ideal body weight), which decreased intraoperative and postoperative opioid requirements and postoperative pain, compared with conventional intermittent short-duration opioids, with similar side effects.

From the *Department of Anesthesiology

Department of Surgery, Washington University in St Louis, St Louis, Missouri

BioRankings, St Louis, Missouri

§Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, St Louis, Missouri

The Center for Clinical Pharmacology, St Louis College of Pharmacy, Washington University in St Louis, St Louis, Missouri.

Published ahead of print 16 April 2018.

Accepted for publication April 16, 2018.

Funding: Supported by grants from the National Institutes of Health (R01 DA042985 to E.D.K.), Barnes-Jewish Hospital Foundation (7957–77 to H.K.), and the Washington University in St Louis Department of Anesthesiology, Division of Clinical and Translational Research (to H.K.).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Registration: (NCT02300077).

Reprints will not be available from the authors.

Address correspondence to Helga Komen, MD, Department of Anesthesiology, Washington University in St Louis, Campus Box 8054, 660 S Euclid Ave, St Louis, MO 63110. Address email to

© 2019 International Anesthesia Research Society
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