The Impact of Intraoperative Methadone on Postoperative Opioid Use

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer; Opioid Use
• Interventions: Drug: Methadon

• Registration Number: NCT07092475
• Lead Sponsor: University of Utah

Brief Summary

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.

Detailed Description

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 Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-07-21
• Last Update Submitted: 2025-07-21
• Study First Posted: 2025-07-30
• Last Update Posted: 2025-07-30
• Study Start: 2025-08-01
• Primary Completion: 2028-08
• Study Completion: 2028-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intraoperative Methadone	Methadon	the methadone group will receive a single dose of intravenous methadone administered within 30 minutes after induction of anesthesia by the attending anesthesiologist. The standard dose will be 20 mg, except for patients under 60 kg or over 65 years of age, who will receive 15 mg.

Primary Outcome Measures

Name	Time	Method
Total Postoperative Opioid Use	from the day of surgery until discharge, up to 4 weeks.	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.

Secondary Outcome Measures

Name	Time	Method
Patient-Reported Pain Scores - Pain Interference Score	from the day of surgery until discharge, up to 4 weeks.	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.
Patient-Reported Pain Scores - Visual Analog Scale	from the day of surgery until discharge, up to 4 weeks.	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.
Patient-Reported Pain Scores - Patient Pain Management Satisfaction Scale	from the day of surgery until discharge, up to 4 weeks.	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.
Length of hospital stay	from the day of surgery until discharge, up to 4 weeks.	To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction.; Length of hospital stay will be captured in 24-hour intervals. This outcome measure will report the mean hospital stay in days.
Proportion of participants utilizing non-opioid analgesics	from the day of surgery until discharge, up to 4 weeks.	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 report the proportion of participants who used non-opioid analgesics such as Tylenol (Acetaminophen) and NSAIDs.
Opioid-related side effects	from the day of surgery until discharge, up to 4 weeks.	To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction.; Patients will be monitored daily for opioid-related side effects, including nausea, vomiting, constipation, sedation, and respiratory depression. This outcome measure will report the proportion of subjects who experience each opioid-related side effect.
Days of non-opioid analgesics use	from the day of surgery until discharge, up to 4 weeks.	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 report the mean days research participants took non-opioid analgesics.
Time to opioid cessation	from the day of surgery until discharge, up to 4 weeks.	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 report the mean time in days to opioid cessation for each group.
Complication Rates	from the day of surgery until discharge, up to 4 weeks.	To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction.; Patients will be monitored daily for surgery complications, including wound issues, seroma/hematoma, infection, takeback to OR, readmission, ED visits, and reoperation. This outcome measure will report the proportion of subjects who experience each complications.

Trial Locations

Locations (1)

Joy Ha; 🇺🇸 Salt Lake City, Utah, United States