The Impact of Intraoperative Methadone on Postoperative Opioid Use

Utah System of Higher Education (USHE)

Status and phase: Withdrawn; Phase 3

Conditions: Breast Cancer; Opioid Use

Treatments: Drug: Methadon

Study type: Interventional

Funder types: Other

Identifiers

NCT07092475

HCI182069

Details and patient eligibility

About

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.

Full 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).

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 2 patient groups

Intraoperative Methadone

Experimental group

Description:

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.

Treatment:

Drug: Methadon

Control

No Intervention group

Description:

The control group will not receive methadone and will instead receive a standard dose of 1 mg IV hydromorphone within the final 30-45 minutes of the procedure.