The Impact of Intraoperative Methadone on Postoperative Opioid Use

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.

Timeline

Start

2025-11

Primary completion

2025-11

Completion

2025-11

Outcome

Outcome not reported

Stopped (Enrollment): “The study team will no longer be enrolling patients for this research.”

Publications

• Background CfDCa Prevention: Opioids. https://www.cdc.gov/opioids/index.html. Accessed October 26, 2021.
• Background Hah JM, Bateman BT, Ratliff J, Curtin C, Sun E. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesth Analg. 2017 Nov;125(5):1733-1740. doi: 10.1213/ANE.0000000000002458.
• Background Olds C, Spataro E, Li K, Kandathil C, Most SP. Assessment of Persistent and Prolonged Postoperative Opioid Use Among Patients Undergoing Plastic and Reconstructive Surgery. JAMA Facial Plast Surg. 2019 Jul 1;21(4):286-291. doi: 10.1001/jamafacial.2018.2035.
• Background Mercadante S. Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Drugs. 2023 Jul;83(10):865-871. doi: 10.1007/s40265-023-01876-7. Epub 2023 Jun 13.
• Background Barker JC, DiBartola K, Wee C, Andonian N, Abdel-Rasoul M, Lowery D, Janis JE. Preoperative Multimodal Analgesia Decreases Postanesthesia Care Unit Narcotic Use and Pain Scores in Outpatient Breast Surgery. Plast Reconstr Surg. 2018 Oct;142(4):443e-450e. doi: 10.1097/PRS.0000000000004804.
• Background Muetterties CE, Taylor JM, Kaeding DE, Morales RR, Nguyen AV, Kwan L, Tseng CY, Delong MR, Festekjian JH. Enhanced Recovery after Surgery Protocol Decreases Length of Stay and Postoperative Narcotic Use in Microvascular Breast Reconstruction. Plast Reconstr Surg Glob Open. 2023 Dec 14;11(12):e5444. doi: 10.1097/GOX.0000000000005444. eCollection 2023 Dec.
• Background Gort N, van Gaal BGI, Tielemans HJP, Ulrich DJO, Hummelink S. Positive effects of the enhanced recovery after surgery (ERAS) protocol in DIEP flap breast reconstruction. Breast. 2021 Dec;60:53-57. doi: 10.1016/j.breast.2021.08.010. Epub 2021 Aug 20.
• Background Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
• Background Kharasch ED, Brunt LM, Blood J, Komen H. Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study. Anesthesiology. 2023 Oct 1;139(4):405-419. doi: 10.1097/ALN.0000000000004663.
• Background Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.
• Background Carle N, Nikolajsen L, Uhrbrand CG. Respiratory Depression Following Intraoperative Methadone: A Retrospective Cohort Study. Anesth Analg. 2025 Mar 1;140(3):516-523. doi: 10.1213/ANE.0000000000007018. Epub 2025 Feb 14.
• Background Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
• Background Bernstein JL, Lu Wang M, Huang H, Otterburn DM. Intra-operative Methadone Decreases Post-operative Pain and Opioid Use in DIEP Flap Breast Patients: A New ERAS Protocol. Plast Reconstr Surg Glob Open. 2022;10(10 Suppl):92. Published 2022 Oct 24. doi:10.1097/01.GOX.0000898792.35273.f6
• Background NIDA. Drug Overdose Deaths: Facts and Figures. National Institute on Drug Abuse website. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates. August 21, 2024 Accessed November 12, 2024.
• Background Centers for Disease Control and Prevention. State Unintentional Drug Overdose Reporting System (SUDORS). Preliminary Data. Atlanta, GA: US Department of Health and Human Services, CDC; November 12, 2024. Access at: https://www.cdc.gov/overdose-prevention/data-research/facts-stats/sudors-dashboard-fatal-overdose-data.html
• Background Florence C, Luo F, Rice K. The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017. Drug Alcohol Depend. 2021 Jan 1;218:108350. doi: 10.1016/j.drugalcdep.2020.108350. Epub 2020 Oct 27.
• Background Meyer R, Patel AM, Rattana SK, Quock TP, Mody SH. Prescription opioid abuse: a literature review of the clinical and economic burden in the United States. Popul Health Manag. 2014 Dec;17(6):372-87. doi: 10.1089/pop.2013.0098.
• Background Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period. JAMA Intern Med. 2016 Sep 1;176(9):1286-93. doi: 10.1001/jamainternmed.2016.3298.
• Background Alam A, Gomes T, Zheng H, Mamdani MM, Juurlink DN, Bell CM. Long-term analgesic use after low-risk surgery: a retrospective cohort study. Arch Intern Med. 2012 Mar 12;172(5):425-30. doi: 10.1001/archinternmed.2011.1827.
• Background Goldberg RF. The Opioid Crisis: The Surgeon's Role. Adv Surg. 2019 Sep;53:305-325. doi: 10.1016/j.yasu.2019.04.015. Epub 2019 May 17. No abstract available.
• Background Theisen K, Jacobs B, Macleod L, Davies B. The United States opioid epidemic: a review of the surgeon's contribution to it and health policy initiatives. BJU Int. 2018 Nov;122(5):754-759. doi: 10.1111/bju.14446. Epub 2018 Jul 26.
• Background Murphy GS, Szokol JW. Intraoperative Methadone in Surgical Patients: A Review of Clinical Investigations. Anesthesiology. 2019 Sep;131(3):678-692. doi: 10.1097/ALN.0000000000002755. No abstract available.
• Background Lai G, Aroke EN, Zhang SJ. Rediscovery of Methadone to Improve Outcomes in Pain Management. J Perianesth Nurs. 2022 Aug;37(4):425-434. doi: 10.1016/j.jopan.2021.08.011. Epub 2022 Apr 6.
• Background Temple-Oberle C, Shea-Budgell MA, Tan M, Semple JL, Schrag C, Barreto M, Blondeel P, Hamming J, Dayan J, Ljungqvist O; ERAS Society. Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations. Plast Reconstr Surg. 2017 May;139(5):1056e-1071e. doi: 10.1097/PRS.0000000000003242.
• Background Jablonka EM, Lamelas AM, Kim JN, Molina B, Molina N, Okwali M, Samson W, Sultan MR, Dayan JH, Smith ML. Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction. Plast Reconstr Surg. 2017 Aug;140(2):240-251. doi: 10.1097/PRS.0000000000003508.
• Background Carron M, Tamburini E, Linassi F, Pettenuzzo T, Boscolo A, Navalesi P. Efficacy of nonopioid analgesics and adjuvants in multimodal analgesia for reducing postoperative opioid consumption and complications in obesity: a systematic review and network meta-analysis. Br J Anaesth. 2024 Dec;133(6):1234-1249. doi: 10.1016/j.bja.2024.08.009. Epub 2024 Oct 3.
• Background Tageza Ilala T, Teku Ayano G, Ahmed Kedir Y, Tamiru Mamo S. Evidence-Based Guideline on the Prevention and Management of Perioperative Pain for Breast Cancer Peoples in a Low-Resource Setting: A Systematic Review Article. Anesthesiol Res Pract. 2023 Nov 3;2023:5668399. doi: 10.1155/2023/5668399. eCollection 2023.
• Background Baratta JL, Schwenk ES, Viscusi ER. Clinical consequences of inadequate pain relief: barriers to optimal pain management. Plast Reconstr Surg. 2014 Oct;134(4 Suppl 2):15S-21S. doi: 10.1097/PRS.0000000000000681.
• Background Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, Lewkowitz AK, Brothers T, Wen X. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Jun 1;3(6):e207367. doi: 10.1001/jamanetworkopen.2020.7367.
• Background Glowacki D. Effective pain management and improvements in patients' outcomes and satisfaction. Crit Care Nurse. 2015 Jun;35(3):33-41; quiz 43. doi: 10.4037/ccn2015440.
• Background Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017 Sep 25;10:2287-2298. doi: 10.2147/JPR.S144066. eCollection 2017.
• Background Sunilkumar MM, Lockman K. Practical Pharmacology of Methadone: A Long-acting Opioid. Indian J Palliat Care. 2018 Jan;24(Suppl 1):S10-S14. doi: 10.4103/IJPC.IJPC_180_17.
• Background Hanna V, Senderovich H. Methadone in Pain Management: A Systematic Review. J Pain. 2021 Mar;22(3):233-245. doi: 10.1016/j.jpain.2020.04.004. Epub 2020 Jun 26.
• Background Komen H, Brunt LM, Deych E, Blood J, Kharasch ED. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Anesth Analg. 2019 Apr;128(4):802-810. doi: 10.1213/ANE.0000000000003464.
• Background Broyles JM, Balk EM, Adam GP, Cao W, Bhuma MR, Mehta S, Dominici LS, Pusic AL, Saldanha IJ. Implant-based versus Autologous Reconstruction after Mastectomy for Breast Cancer: A Systematic Review and Meta-analysis. Plast Reconstr Surg Glob Open. 2022 Mar 11;10(3):e4180. doi: 10.1097/GOX.0000000000004180. eCollection 2022 Mar.
• Background Jacobs A, Lemoine A, Joshi GP, Van de Velde M, Bonnet F; PROSPECT Working Group collaborators#. PROSPECT guideline for oncological breast surgery: a systematic review and procedure-specific postoperative pain management recommendations. Anaesthesia. 2020 May;75(5):664-673. doi: 10.1111/anae.14964. Epub 2020 Jan 26.
• Background Roth RS, Lowery JC, Davis J, Wilkins EG. Persistent pain following postmastectomy breast reconstruction: long-term effects of type and timing of surgery. Ann Plast Surg. 2007 Apr;58(4):371-6. doi: 10.1097/01.sap.0000239810.38137.84.
• Background Cata JP, Zaidi Y, Guerra-Londono JJ, Kharasch ED, Piotrowski M, Kee S, Cortes-Mejia NA, Gloria-Escobar JM, Thall PF, Lin R. Intraoperative methadone administration for total mastectomy: A single center retrospective study. J Clin Anesth. 2024 Nov;98:111572. doi: 10.1016/j.jclinane.2024.111572. Epub 2024 Aug 23.
• Background Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.
• Background Gordon DB, Dahl JL, Miaskowski C, McCarberg B, Todd KH, Paice JA, Lipman AG, Bookbinder M, Sanders SH, Turk DC, Carr DB. American pain society recommendations for improving the quality of acute and cancer pain management: American Pain Society Quality of Care Task Force. Arch Intern Med. 2005 Jul 25;165(14):1574-80. doi: 10.1001/archinte.165.14.1574.
• Background Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain. 2003 Sep;4(7):407-14. doi: 10.1016/s1526-5900(03)00716-8.

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