{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:50:35Z","timestamp":1778187035938,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01HD116257"],"award-info":[{"award-number":["U01HD116257"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Introduction: Methadone is an opioid-sparing opioid and it is increasingly used in children undergoing surgery due to its beneficial effects on postoperative pain scores, decreased opioid requirements, and fewer adverse effects compared to other opioids. Intraoperative methadone is not well studied in pediatric cardiac surgery. We hypothesized that intraoperative methadone-based analgesia would provide comparable effectiveness in pain management to non-methadone-based analgesia, including caudal morphine, following pediatric cardiac surgery. Methods: We conducted a retrospective cohort study of 287 children undergoing cardiac surgery using single institutional electronic health records with Society of Thoracic Surgeons database outcomes. Patients were administered intravenous opioids plus caudal morphine (\u22646 years) or intravenous opioids in the non-methadone group versus intravenous methadone (two 0.1 mg\/kg doses given intraoperatively) with or without additional intraoperative opioids. The primary outcome was postoperative opioid use in morphine milligram equivalents (MME)\/kg. Results: This study included 287 pediatric cardiac surgical patients with a mean age of 3.8 years, 59% male, and 72% White. Among 287 patients, 67 (23%) received intraoperative methadone. Unadjusted analysis showed the methadone group had lower postoperative opioid use on the day of surgery (median = 0.3 vs. 0.5 MME\/kg, p = 0.005). Adjusted analyses showed there were no significant differences in postoperative opioid use, average pain, maximum pain, antiemetic use, reintubation, and use of naloxone between methadone and non-methadone groups. Hospital length of stay was 2.62 times longer (95% CI: [1.55, 4.41] p &lt; 0.001) in the methadone group vs non-methadone group, but this was only shown in the younger children (\u22646 years), who also had higher max pain scores in the methadone group. All outcomes were similar between analgesia groups in older children (&gt;6 years). Conclusions: Intraoperative methadone-based analgesia had comparable effectiveness in postoperative opioid use, pain, and antiemetic use compared to non-methadone-based intraoperative pain management for pediatric cardiac surgery. Large prospective studies of perioperative methadone are needed to examine methadone\u2019s analgesic benefits in children undergoing cardiac surgery.<\/jats:p>","DOI":"10.3390\/children12050567","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T03:50:43Z","timestamp":1746071443000},"page":"567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intraoperative Methadone Versus Non-Methadone Analgesia in Pediatric Cardiac Surgery: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Brian","family":"Blasiole","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle R.","family":"Lavage","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-9830","authenticated-orcid":false,"given":"Hsing-Hua Sylvia","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-583X","authenticated-orcid":false,"given":"Scott E.","family":"Licata","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahana","family":"Sivam","sequence":"additional","affiliation":[{"name":"North Allegheny High School, Pittsburgh, PA 15090, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inesh","family":"Sivam","sequence":"additional","affiliation":[{"name":"North Allegheny High School, Pittsburgh, PA 15090, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Le","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-8313","authenticated-orcid":false,"given":"Senthilkumar","family":"Sadhasivam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.jpain.2014.08.010","article-title":"The fentanyl story","volume":"15","author":"Stanley","year":"2014","journal-title":"J. Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/2049463712438493","article-title":"Basic opioid pharmacology: An update","volume":"6","author":"Pathan","year":"2012","journal-title":"Br. J. Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2165\/00003088-199631040-00004","article-title":"Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. An update","volume":"31","author":"Scholz","year":"1996","journal-title":"Clin. Pharmacokinet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1208","DOI":"10.1542\/peds.2009-0489","article-title":"Tolerance and withdrawal from prolonged opioid use in critically ill children","volume":"125","author":"Anand","year":"2010","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/pan.12990","article-title":"Caudal analgesia and cardiothoracic surgery: A look at postoperative pain scores in a pediatric population","volume":"26","author":"Nguyen","year":"2016","journal-title":"Paediatr. Anaesth."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/00000542-198903000-00009","article-title":"Caudal epidural morphine for control of pain following open heart surgery in children","volume":"70","author":"Rosen","year":"1989","journal-title":"Anesthesiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/AAP.0000000000000763","article-title":"Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition)","volume":"43","author":"Horlocker","year":"2018","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1213\/ANE.0000000000006790","article-title":"Methadone and Enhanced Recovery After Surgery: Concepts and Protocols","volume":"139","author":"Ramaiah","year":"2024","journal-title":"Anesth. Analg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1053\/j.jvca.2024.02.022","article-title":"Pro: Methadone Should Be Used as a Part of Enhanced Recovery After Cardiac Surgery Protocol","volume":"38","author":"Garcia","year":"2024","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1213\/ANE.0000000000005366","article-title":"A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects","volume":"133","author":"Sadhasivam","year":"2021","journal-title":"Anesth. Analg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e336","DOI":"10.1097\/pq9.0000000000000336","article-title":"Methadone-Based Multimodal Analgesia Provides the Best-in-Class Acute Surgical Pain Control and Functional Outcomes with Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents with Idiopathic Scoliosis","volume":"5","author":"Ye","year":"2020","journal-title":"Pediatr. Qual. Saf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1111\/pan.13903","article-title":"The effect of intraoperative methadone during pediatric cardiac surgery on postoperative opioid requirements","volume":"30","author":"Barnett","year":"2020","journal-title":"Paediatr. Anaesth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1001\/jamasurg.2023.2009","article-title":"Association of Intraoperative Opioid Administration With Postoperative Pain and Opioid Use","volume":"158","author":"Liu","year":"2023","journal-title":"JAMA Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/pds.3945","article-title":"A synthesis of oral morphine equivalents (OME) for opioid utilisation studies","volume":"25","author":"Nielsen","year":"2016","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_15","first-page":"293","article-title":"The FLACC: A behavioral scale for scoring postoperative pain in young children","volume":"23","author":"Merkel","year":"1997","journal-title":"Pediatr. Nurs."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1460-9592.1995.tb00242.x","article-title":"CRIES: A new neonatal postoperative pain measurement score. Initial testing of validity and reliability","volume":"5","author":"Krechel","year":"1995","journal-title":"Paediatr. Anaesth."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/psp4.12687","article-title":"Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children","volume":"10","author":"Aruldhas","year":"2021","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2217\/pgs-2021-0039","article-title":"Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children","volume":"22","author":"Packiasabapathy","year":"2021","journal-title":"Pharmacogenomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1213\/ANE.0000000000006331","article-title":"Pro-Con Debate: Role of Methadone in Enhanced Recovery After Surgery Protocols-Superior Analgesic or Harmful Drug?","volume":"137","author":"Esfahani","year":"2023","journal-title":"Anesth. Analg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/ALN.0000000000003025","article-title":"Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery","volume":"132","author":"Murphy","year":"2020","journal-title":"Anesthesiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1097\/ALN.0000000000001609","article-title":"Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial","volume":"126","author":"Murphy","year":"2017","journal-title":"Anesthesiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1053\/j.jvca.2024.11.012","article-title":"Intraoperative Methadone in Adult Cardiac Surgical Patients and Risks for Postoperative QTc Prolongation","volume":"39","author":"McClain","year":"2025","journal-title":"J. Cardiothorac. Vasc. Anesth."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/5\/567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:23:15Z","timestamp":1760030595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/5\/567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["children12050567"],"URL":"https:\/\/doi.org\/10.3390\/children12050567","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]}}}