Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study

Published:November 04, 2019DOI:


      To determine if there is an association of intraoperative methadone use and total perioperative opioid exposure in patients undergoing congenital heart surgeries.


      Retrospective, case-match cohort study.


      Single center quaternary care teaching hospital.


      Seventy-four patients with congenital heart disease (CHD) undergoing surgical repair or palliative surgery.


      Thirty-seven patients undergoing CHD surgeries receiving intraoperative methadone were matched to 37 patients based upon age and procedure who did not receive intraoperative methadone. The primary study outcome was to evaluate total opioid use in intravenous milligrams of morphine equivalents per kilogram (mg ME/kg) within the first 36-hours postoperatively. Mann-Whitney U test was used to compare total opioid exposure.

      Measurements and Main Results

      The total opioid use was compared between groups. The methadone cohort required less opioids intraoperatively, in the first 12 hours postoperatively, and during the first 36 hours postoperatively (2.51 v 4.39 mg ME/kg, p < 0.001; 0.43 v 1.28 mg ME/kg, p = 0.001; and 0.83 v 1.91 mg ME/kg, p < 0.001) compared with the matched control cohort. There were no differences in clinical outcomes or adverse events. A dose-dependent reduction in opioid consumption in high- versus low-dose groups also was not observed.


      Intraoperative methadone use was associated with a decrease in perioperative opioid exposure in patients undergoing congenital heart surgery and was not associated with adverse events or prolonged durations of mechanical ventilation or ICU stay.

      Key Words

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        • Bovill J.G.
        • Sebel P.S.
        • Stanley T.H.
        Opioid analgesics in anesthesia: With special reference to their use in cardiovascular anesthesia.
        Anesthesiology. 1984; 61: 731-755
        • Barletta J.F.
        Clinical and economic burden of opioid use for postsurgical pain: Focus on ventilatory impairment and ileus.
        Pharmacotherapy. 2012; 32: 12S-18S
        • Gupta A.
        • Daggett C.
        • Drant S.
        • et al.
        Prospective randomized trial of ketorolac after congenital heart surgery.
        J Cardiothorac Vasc Anesth. 2004; 18: 454-457
        • Naguib A.N.
        • Dewhirst E.
        • Winch P.D.
        • et al.
        Pain management after surgery for single-ventricle palliation using the hybrid approach.
        Pediatr Cardiol. 2012; 33: 1104-1108
        • Krishna S.N.
        • Caudhan S.
        • Bhoi D.
        • et al.
        Bilateral erector spinae plane block for acute post-surgical pain in adult cardiac surgical patients: A randomized controlled trial.
        J Cardiothorac Vasc Anesth. 2019; 33: 368-375
        • Esfahanian M.
        • Caruso T.J.
        • Lin C.
        • et al.
        Toward opioid-free fast track for pediatric congenital cardiac surgery.
        J Cardiothorac Vasc Anesth. 2019; 33: 2362-2363
        • Murphy G.S.
        • Szokol J.W.
        • Avram M.J.
        • et al.
        Intraoperative methadone for the prevention of postoperative pain.
        Anesthesiology. 2015; 122: 1112-1122
        • Berde C.B.
        • Beyer J.E.
        • Bournaki M.C.
        • et al.
        Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children.
        J Pediatr. 1991; 119: 136-141
        • Murphy G.S.
        • Szokol J.W.
        • Avram M.J.
        • et al.
        Clinical effectiveness and safety of intraoperative methadone in patients undergoing posterior spinal fusion surgery.
        Anesthesiology. 2017; 126: 822-833
        • Gottschalk A.
        • Durieux M.E.
        • Nemergut E.C.
        Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery.
        Anesth Analg. 2011; 112: 218-223
        • Udelsmann A.
        • Maciel F.G.
        • Servian D.C.
        • et al.
        Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting.
        Rev Bras Anestesiol. 2011; 61: 695-701
        • Singhal N.R.
        • Jones J.
        • Semenova J.
        • et al.
        Multimodal anesthesia with the addition of methadone is superior to epidural analgesia: A retrospective comparison of intraoperative anesthetic techniques and pain management for 124 pediatric patients undergoing the Nuss procedure.
        J Pediatr Surg. 2016; 51: 612-616
        • Barr J.
        • Zomorodi K.
        • Bertaccini E.J.
        • et al.
        A double-blind, randomized comparison of IV lorazepam versus midazolman for sedation in ICU patients via a pharmacologic model.
        Anesthesiology. 2001; 95: 286-298
        • Rodgers A.
        • Walker N.
        • Schug S.
        • et al.
        Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from overview of randomized trials.
        BMJ. 2000; 321: 1493
        • O'Neill P.
        • Knickenberg C.
        • Bogahalanda S.
        • et al.
        Use of intrathecal morphine for postoperative pain relief following lumbar spine surgery.
        J Neurosurg. 1985; 63: 413-416
        • Barletta J.F.
        • Shintani A.
        • Truman B.
        • et al.
        Clinical and economic burden of opioid use for postsurgical pain: focus on ventilator impairment and ileus.
        Pharmacotherapy. 2012; 32 (12S–8S)
        • Stemland C.J.
        • Witte J.
        • Coluhoun D.A.
        • et al.
        The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion.
        Paediatr Anaesth. 2013; 23: 51-57
        • Newburger J.W.
        • Wypij D.
        • Bellinger D.C.
        • et al.
        Length of stay after infant heart surgery is related to cognitive outcome at age 8 years.
        J Pediatr. 2003; 143: 67-73
        • Pasquali S.K.
        • He X.
        • Jacobs M.L.
        • et al.
        Excess costs associated with complications and prolonged length of stay after congenital heart surgery.
        Ann Thorac Surg. 2014; 98: 1660-1666
        • Gaies M.
        • Pasquali S.K.
        • Nicolson S.C.
        • et al.
        Sustainability of infant cardiac surgery early extubation practices after implementation and study.
        Ann Thorac Surg. 2018;
        • Kornick C.A.
        • Kilborn M.J.
        • Santiago-Palma J.
        • et al.
        QTc interval prolongation associated with intravenous methadone.
        Pain. 2003; 105: 499-506
        • Joyce D.D.
        • Bos J.M.
        • Haugaa K.H.
        • et al.
        Frequency and cause of transient QT prolongation after surgery.
        Ann J Cardiol. 2015; 116: 1605-1609

      Linked Article

      • Is Methadone an Opioid Sparing Strategy?
        Journal of Cardiothoracic and Vascular AnesthesiaVol. 34Issue 2
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          IN THIS ISSUE OF THE Journal of Cardiothoracic and Vascular Anesthesia, Robinson et al. sought to determine whether intraoperative methadone administration decreases acute perioperative opioid use in children undergoing congenital heart surgery.1 This is a particularly important question in an era in which the opioid epidemic has emerged as a forefront issue, emphasizing the importance of improving the quality of healthcare such that it is safer and more effective. While adult perioperative opioid prescribing patterns have been well recognized as contributory to this crisis, the pediatric surgical population is also vulnerable.
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