The Impact of Intraoperative Methadone on Postoperative Opioid Use

University of Utah

Overview

This is a single-institution, randomized controlled trial to assess the effectiveness of intraoperative methadone on postoperative opioid use, pain control, and recovery in patients undergoing autologous breast reconstruction. Findings from this trial would inform subsequent perioperative pain protocols and allow the possible integration of intraoperative methadone into multimodal analgesia protocols.

Opioid over prescription remains a significant contributor to the opioid crisis in the United States. One major contributor to this epidemic is postoperative opioid prescribing-over 80% of surgical patients receive opioids for postoperative pain, placing many, especially opioid-naive patients, at risk for prolonged use, dependence, and addiction. Many traditional pain management interventions rely on high doses of short-acting opioids such as hydromorphone and fentanyl. Though effective in the short term, these medications often have fluctuating blood concentration levels, which can lead to ineffective pain control, increased side effects, and higher risk for long-term dependence and chronic use. Despite national efforts to promote better recovery pathways through multimodal pain management plans, significant variation in postoperative opioid prescribing and consumption patterns remains, and over 40% of surgical patients still do not achieve adequate relief of pain. An alternative solution is intraoperative methadone, a long-acting synthetic opioid with a pharmacologic profile that potentially offers more stable and longer-lasting pain relief. Unlike short-acting opioids, a single dose of methadone given intraoperatively has been shown to be capable of maintaining analgesic levels for up to 24-36 hours, potentially reducing total postoperative opioid requirements. The use of intraoperative methadone for cardiac, spine, and ambulatory procedures is well-established, demonstrating that methadone leads to significant reductions in perioperative opioid use and pain scores postoperatively without increased risk of opioid side effects. In addition, preliminary data from a 2022 study on DIEP flap patients and a 2024 retrospective cohort study on mastectomy patients both suggest that intraoperative methadone significantly reduces postoperative opioid requirements. Preliminary retrospective data from revealed that patients receiving intraoperative methadone for autologous breast reconstruction had significantly lower postoperative opioid consumption compared to those who did not receive intraoperative methadone, with a 37.2% reduction in total inpatient opioid use. However, prospective, randomized data in this population is currently lacking. This is a single-institution, randomized controlled trial to assess the effectiveness of intraoperative methadone on postoperative opioid use, pain control, and recovery in patients undergoing autologous breast reconstruction. Findings from this trial would inform subsequent perioperative pain protocols and allow the possible integration of intraoperative methadone into multimodal analgesia protocols. Patients will be randomized to either a methadone cohort or a control cohort. Aside from this intervention, both groups will undergo the same standardized intraoperative anesthetic protocol. Surgical care will not be altered for study purposes. Postoperative care will follow institutional protocols and will not be altered for study purposes. Patients in both cohorts will receive the same standardized postoperative analgesic regimen, including as-needed (PRN) administration of short-acting opioids (e.g., IV hydromorphone, IV fentanyl), acetaminophen, and antiemetics. NSAIDs such as ketorolac or celecoxib will be avoided. Patients will be monitored daily for opioid-related side effects including nausea, vomiting, constipation, sedation, and respiratory depression. Nausea will be assessed both through direct patient report and review of antiemetic administration (e.g., ondansetron, metoclopramide).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

DOUBLE

Conditions

Breast Cancer Opioid Use

Interventions

MethadonDRUG

A long-acting synthetic opioid with a pharmacologic profile that potentially offers more stable and longer-lasting pain relief.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Female patients 18 years of age or older * Patients undergoing unilateral or bilateral autologous breast reconstruction with abdominally-based free flaps after mastectomy for breast cancer or cancer prophylaxis Exclusion Criteria: * Patients undergoing reoperations such as autologous breast reconstruction as a revision procedure following failed implant-based reconstruction * Patients undergoing multiple procedures such as mastectomy and immediate reconstruction * Patients with documented chronic opioid use prior to procedure, or chronic pain condition

Locations (1)

Joy Ha

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

Total Postoperative Opioid Use

To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction. Total perioperative opioid consumption will be measured in morphine milligram equivalents (MMEs), a standardized measure to quantify the strength of opioid doses compared to morphine. This outcome measure will be assessed from the day of surgery until discharge, up to 4 weeks.

Time frame: from the day of surgery until discharge, up to 4 weeks.

Secondary Outcomes

Patient-Reported Pain Scores - Visual Analog Scale

To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction. This outcome measure will assess visual analog scale scores, a measurement to assess pain by having subjects mark pain on a line. Visual analog scale scores range from 0-10, with lower scores indicating less perceived pain and higher scores indicating more perceived pain.

Time frame: from the day of surgery until discharge, up to 4 weeks.

Patient-Reported Pain Scores - Pain Interference Score

To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction. This outcome measure will assess pain interference scores, a measure for assessing how pain impacts daily life. Pain Interference scores range from 0-10, with lower scores indicating less interference with daily life and higher scores indicating more interference with daily life.

Time frame: from the day of surgery until discharge, up to 4 weeks.

Patient-Reported Pain Scores - Patient Pain Management Satisfaction Scale

To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction. This outcome measure will assess patient pain management satisfaction scale scores in the immediate postoperative period. The Patient Pain Management Satisfaction Scale is a single-item, self-reported question, "Please write your satisfaction with your pain management". Patient Pain Management Satisfaction Scale scores range from 0 to 100, with lower scores indicating worse satisfaction with pain management and higher scores indicating better satisfaction with pain management.

Data from ClinicalTrials.gov

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