The impact of intraoperative methadone on perioperative opioid requirements in autologous free flap breast reconstruction

Authors: Somers S, Vitale A, Dadzie A, French M, Eddington D, Agarwal JP, Kwok AC.

Affiliation: Division of Plastic & Reconstructive Surgery, University of Utah

Journal: Journal of Reconstructive Microsurgery, September 2025.

PMID: 41067267

Key takeaways

• A single induction dose of methadone (typically 20 mg IV) lowered postoperative (Day 0-2) and total inpatient opioid use versus standard care.

• Mean cumulative inpatient opioid administration fell ~37% (87.4 vs 139.1 MME; p=0.03) with methadone use.

• Antiemetic use was similar between groups.

• Length of stay was similar (3.2 vs 3.5 days; p=0.14).

Background

Enhanced recovery pathways for DIEP and other free flaps attempt to minimize opioid consumption to reduce opioid related side effects, such and nausea/vomiting and opioid dependency. Methadone’s long half-life and NMDA antagonism support single-dose intraoperative use.

Objective

Assess whether intraoperative methadone reduces perioperative opioid requirements after autologous free-flap breast reconstruction.

Methods

• Design/setting/LOE: Single-center retrospective cohort; July 2023–August 2024; Level III evidence.

• Cohorts: Practice change implemented June 2024. Patients before = no methadone; after = methadone. Chronic opioid users excluded.

• Dose/timing: 10–30 mg IV at induction; 69% received 20 mg.

• Sample: 112 total patients (methadone 58; control 54). Mean age 49 both groups. BMI slightly lower with methadone (28.1 vs 30.9).

• Procedures: Predominantly DIEP (~93%); mean operative time ~7.3 hours; similar between groups.

• Analgesic protocol: Standard inpatient acetaminophen ± ketorolac. Early ketorolac use higher in methadone cohort; addressed in modeling and subgroup analyses. No routine regional blocks.

• Primary endpoint: Daily inpatient opioid use (morphine milligram equivalents, MME) POD0–POD4.

• Secondary endpoints: Intraoperative opioid use; acetaminophen/ketorolac exposure; frequency of antiemetic doses; length of stay.

• Statistics: Group tests plus two-step modeling—logistic regression for any opioid use and linear mixed-effects for daily MME; α=0.05.

Results

• Intraoperative opioids: Additional short-acting opioids lower with methadone (4.1 vs 21.3 MME; ~81% reduction).

• Postoperative opioid use, methadone group vs control (mean MME):

  • POD0: 18.8 vs 27.9 (p=0.06)

  • POD1: 29.0 vs 44.4 (p=0.039)

  • POD2: 22.9 vs 38.7 (p=0.04)

  • POD3–4: no significant differences

  • Cumulative inpatient: 87.4 vs 139.1 (p=0.03)

• Modeling: Methadone associated with a 26% decrease in daily MME after adjusting for POD, ketorolac dose, BMI, and laterality.

• Antiemetics: No difference in antiemetic dosing frequency.

• Length of stay: 3.2 vs 3.5 days; not significant.

Conclusion

A single induction dose of methadone (typically 20 mg IV) reduces postoperative and total inpatient opioid requirements after autologous free-flap reconstruction without observed safety penalties or longer stays.

Strengths & limitations

• Strengths: Contemporary cohort during a defined practice change; standardized POD0–4 endpoints; appropriate mixed-effects modeling.

• Limitations: Retrospective, single-center, non-blinded; BMI imbalance and greater early ketorolac use; limited capture of adverse effects and pain scores.

Clinical relevance

Plastic surgeons should consider a single induction dose of methadone 20 mg IV. It appears to be a pragmatic adjunct that lowers early and total inpatient opioid needs without negative safety effects. Implement with QT-risk screening, respiratory monitoring (RR, SpO₂/EtCO₂), and structured nursing sedation checks.

Critiques and questions

• Patient-centered outcomes: Pain scores, sleep quality, mobilization milestones, and satisfaction were not reported; these would clarify functional benefits.

• Safety capture: No opioid-related adverse events were recorded, but retrospective designs often miss respiratory events, QTc changes, or PACU delays. Prospective monitoring—including naloxone use, apnea episodes, and QTc—is warranted.