{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T02:46:43Z","timestamp":1777344403573,"version":"3.51.4"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To compare efficacy of oral versus intravenous (IV) methadone on postoperative pain and opioid requirements after spine surgery.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a retrospective, single-academic center cohort study evaluating 1010 patients who underwent &gt;3 level spine surgery from January 2017 to May 2020 and received a one-time dose of oral or intravenous methadone prior to surgery. The primary outcome measured was postoperative opioid use in oral morphine equivalents (ME) and verbal response scale (VRS) pain scores up to postoperative day (POD) three. Secondary outcomes were time to first bowel movement and adverse effects (reintubation, myocardial infarction, and QTc prolongation) up to POD 3.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 687 patients received oral and 317 received IV methadone, six patients were excluded. The IV group received a significantly greater methadone morphine equivalent (ME) dose preoperatively (112.4 \u00b1 83.0 mg ME versus 59.3 \u00b1 60.9 mg ME, p &lt; 0.001) and greater total (methadone and non-methadone) opioid dose (119.1 \u00b1 81.4 mg ME versus 63.9 \u00b1 62.5 mg ME, p &lt; 0.001), intraoperatively. Although pain scores for the oral group were non-inferior to the IV group for all postoperative days (POD), non-inferiority for postoperative opioid requirements was demonstrated only on POD 3. Based on the joint hypothesis for the co-primary outcomes, oral methadone was non-inferior to IV methadone on POD 3 only. No differences in secondary outcomes, including QTc prolongation and arrhythmias, were noted between the groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Oral methadone is a feasible alternative to IV methadone for patients undergoing spine surgery regarding both pain scores and postoperative opioid consumption.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0288988","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T17:36:27Z","timestamp":1689960987000},"page":"e0288988","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of oral versus intravenous methadone on postoperative pain and opioid use after adult spinal deformity surgery: A retrospective, non-inferiority analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-6661","authenticated-orcid":true,"given":"Kamilla","family":"Esfahani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Tennant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siny","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhiken I.","family":"Naik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-2068","authenticated-orcid":true,"given":"Lauren K.","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"issue":"4","key":"pone.0288988.ref001","doi-asserted-by":"crossref","first-page":"e115576","DOI":"10.5812\/aapm.115576","article-title":"Comparison of Intraoperative Infusion of Remifentanil Versus Fentanyl on Pain Management in Patients Undergoing Spine Surgery: A Double Blinded Randomized Clinical Trial.","volume":"11","author":"R Shariat Moharari","year":"2021","journal-title":"Anesth Pain Med"},{"issue":"4","key":"pone.0288988.ref002","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/j.1532-2149.2012.00211.x","article-title":"The impact of intra-operative sufentanil dosing on post-operative pain, hyperalgesia and morphine consumption after cardiac surgery.","volume":"17","author":"J Fechner","year":"2013","journal-title":"Eur J Pain."},{"issue":"6","key":"pone.0288988.ref003","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/bja\/aeu137","article-title":"Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis","volume":"112","author":"D Fletcher","year":"2014","journal-title":"Br J Anaesth"},{"issue":"2","key":"pone.0288988.ref004","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1017\/S1478951508000254","article-title":"Consensus guideline on parenteral methadone use in pain and palliative care","volume":"6","author":"L Shaiova","year":"2008","journal-title":"Palliat Support Care"},{"issue":"1","key":"pone.0288988.ref005","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1213\/ANE.0b013e3181fec9a3","article-title":"Intraoperative methadone: rediscovery, reappraisal, and reinvigoration?","volume":"112","author":"ED Kharasch","year":"2011","journal-title":"Anesth Analg"},{"issue":"1","key":"pone.0288988.ref006","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1213\/ANE.0b013e3181d8a095","article-title":"Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery","volume":"112","author":"A Gottschalk","year":"2011","journal-title":"Anesth Analg"},{"issue":"6","key":"pone.0288988.ref007","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1213\/ANE.0000000000004404","article-title":"Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis.","volume":"129","author":"FC Machado","year":"2019","journal-title":"Anesth Analg"},{"issue":"2","key":"pone.0288988.ref008","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":"GS Murphy","year":"2020","journal-title":"Anesthesiology"},{"issue":"4","key":"pone.0288988.ref009","doi-asserted-by":"crossref","first-page":"681","DOI":"10.21037\/jss-20-629","article-title":"Multi-modal pain control regimen for anterior lumbar fusion drastically reduces in-hospital opioid consumption","volume":"6","author":"Y Ogura","year":"2020","journal-title":"J Spine Surg"},{"issue":"6","key":"pone.0288988.ref010","doi-asserted-by":"crossref","first-page":"e0234199","DOI":"10.1371\/journal.pone.0234199","article-title":"Impact of a perioperative oral opioid substitution protocol during the nationwide intravenous opioid shortage: A single center, interrupted time series with segmented regression analysis.","volume":"15","author":"R Salajegheh","year":"2020","journal-title":"PLoS One."},{"key":"pone.0288988.ref011","volume-title":"Standard Price List","author":"UVA","year":"2022"},{"key":"pone.0288988.ref012","unstructured":"CDC. Calculating Total Daily Dose of Opioids for Safer Dosage: Centers for Disease Control and Prevention; [Cited 1 June 2022] [Available from: https:\/\/www.cdc.gov\/drugoverdose\/pdf\/calculating_total_daily_dose-a.pdf."},{"key":"pone.0288988.ref013","author":"FDA","year":"2015","journal-title":"Full Prescribing Information for Dolophine (Methadone Hydrochloride)"},{"issue":"1","key":"pone.0288988.ref014","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/24740527.2019.1575695","article-title":"Preoperative oral methadone for postoperative pain in patients undergoing cardiac surgery: A randomized double-blind placebo-controlled pilot","volume":"3","author":"TM Bolton","year":"2019","journal-title":"Can J Pain"},{"issue":"1","key":"pone.0288988.ref015","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/00000542-198407000-00005","article-title":"Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration\u2014response relationships","volume":"61","author":"GK Gourlay","year":"1984","journal-title":"Anesthesiology"},{"issue":"4","key":"pone.0288988.ref016","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1213\/ANE.0000000000003464","article-title":"Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.","volume":"128","author":"H Komen","year":"2019","journal-title":"Anesth Analg."},{"issue":"3","key":"pone.0288988.ref017","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1097\/ALN.0b013e3181986a9a","article-title":"Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal drug transport: insights from methadone interactions with ritonavir\/indinavir.","volume":"110","author":"ED Kharasch","year":"2009","journal-title":"Anesthesiology"},{"issue":"3","key":"pone.0288988.ref018","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.clpt.2004.05.003","article-title":"Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone","volume":"76","author":"ED Kharasch","year":"2004","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"pone.0288988.ref019","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.2217\/pgs.14.56","article-title":"Pharmacogenomics of methadone maintenance treatment","volume":"15","author":"AA Somogyi","year":"2014","journal-title":"Pharmacogenomics"},{"issue":"2","key":"pone.0288988.ref020","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/cpdd.326","article-title":"Current Concepts in Methadone Metabolism and Transport","volume":"6","author":"ED Kharasch","year":"2017","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"3","key":"pone.0288988.ref021","first-page":"1021","article-title":"Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation.","volume":"298","author":"Y Oda","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"issue":"14","key":"pone.0288988.ref022","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00003088-200241140-00003","article-title":"Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence.","volume":"41","author":"CB Eap","year":"2002","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"pone.0288988.ref023","doi-asserted-by":"crossref","first-page":"623","DOI":"10.14444\/7083","article-title":"Enhanced Recovery After Surgery Trends in Adult Spine Surgery: A Systematic Review.","volume":"14","author":"Y Tong","year":"2020","journal-title":"Int J Spine Surg"},{"issue":"9","key":"pone.0288988.ref024","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00586-013-2826-1","article-title":"A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery","volume":"22","author":"O Mathiesen","year":"2013","journal-title":"Eur Spine J"},{"issue":"5","key":"pone.0288988.ref025","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3171\/2018.4.SPINE171317","article-title":"Implementation of an Enhanced Recovery After Spine Surgery program at a large cancer center: a preliminary analysis","volume":"29","author":"RM Grasu","year":"2018","journal-title":"J Neurosurg Spine"},{"key":"pone.0288988.ref026","article-title":"Incremental Cost-effectiveness Analysis on Length of Stay of an Enhanced Recovery After Spine Surgery Program: A Single-center, Retrospective Cohort Study.","author":"BI Naik","year":"2021","journal-title":"J Neurosurg Anesthesiol"},{"issue":"9","key":"pone.0288988.ref027","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1097\/EJA.0000000000001448","article-title":"(ESRA) PWgotESoRAaPt. Pain management after complex spine surgery: A systematic review and procedure-specific postoperative pain management recommendations","volume":"38","author":"P Waelkens","year":"2021","journal-title":"Eur J Anaesthesiol"},{"issue":"2","key":"pone.0288988.ref028","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/ALN.0000000000003428","article-title":"Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis","volume":"133","author":"M Verret","year":"2020","journal-title":"Anesthesiology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T17:36:47Z","timestamp":1689961007000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288988"}},"subtitle":[],"editor":[{"given":"Shweta Rahul","family":"Yemul Golhar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0288988","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]}}}