{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:30:14Z","timestamp":1793809814476,"version":"4.6.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Methadone is used as a perioperative analgesic in the management of postoperative pain. Despite positive outcomes from randomized trials favoring methadone, concerns about its safety persist, particularly regarding respiratory depression (RD) and excessive sedation. In this study, we compared the incidence of naloxone administration between patients administered intraoperative methadone and those administered intraoperative morphine as a measure of severe RD. Time spent at the postanesthesia care unit (PACU) was used as a proxy variable for excessive sedation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>This was a retrospective cohort study including all patients aged \u226518 years who underwent surgery between March 2019 and March 2023 at Aarhus University Hospital, Denmark. We assessed the association between intraoperative administration of either methadone or morphine and postoperative naloxone administration within the first 24 hours using logistic regression (primary outcome). An analogous linear regression model was used for the secondary outcome of time spent in the PACU after surgery. Patients were weighted using propensity scores to adjust for potential confounding variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>A total of 14,522 patients were included in the analysis. Among the 2437 patients who received intraoperative methadone, 15 (0.62%) patients received naloxone within the first 24 hours after surgery compared to 68 of 12,0885 (0.56%) who received intraoperative morphine. No statistical difference was observed in the odds of naloxone administration between patients administered methadone or morphine (adjusted odds ratio 95% confidence interval [CI], 1.21 [0.40\u20132.02]). Patients who were administered intraoperative methadone had a mean PACU length of stay (LOS) of 334 minutes (standard deviation [SD], 382) compared to 195 minutes (SD, 228) for those administered intraoperative morphine. The adjusted PACU LOS of patients administered intraoperative methadone was 26% longer compared to those administered intraoperative morphine (adjusted ratio of the geometric means 95% CI, 1.26 [1.22\u20131.31]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The incidence of naloxone administration to treat severe RD was low. No difference was observed in the odds of naloxone administration to treat severe RD between patients administered intraoperative methadone or intraoperative morphine. Intraoperative methadone was associated with longer stays at the PACU; however, this result should be interpreted with care. Our findings suggest that intraoperative methadone has a safety profile comparable to that of morphine with regard to severe RD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1213\/ane.0000000000007018","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T11:04:17Z","timestamp":1717067057000},"page":"516-523","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Respiratory Depression Following Intraoperative Methadone: A Retrospective Cohort Study"],"prefix":"10.1213","volume":"140","author":[{"given":"Nicolai","family":"Carl\u00e9","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lone","family":"Nikolajsen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla G.","family":"Uhrbrand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"R1-20250224","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1213\/ANE.0b013e3181fec9a3","article-title":"Intraoperative methadone: rediscovery, reappraisal, and reinvigoration?","volume":"112","author":"Kharasch","year":"2011","journal-title":"Anesth Analg"},{"key":"R2-20250224","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.phrs.2009.04.002","article-title":"Cooperative N-methyl-D-aspartate (NMDA) receptor antagonism and mu-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain.","volume":"60","author":"Sotgiu","year":"2009","journal-title":"Pharmacol Res"},{"key":"R3-20250224","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0022-3565(25)10630-7","article-title":"Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception.","volume":"274","author":"Codd","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"R4-20250224","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0024-3205(02)02220-8","article-title":"Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats.","volume":"72","author":"Rojas-Corrales","year":"2002","journal-title":"Life Sci"},{"key":"R5-20250224","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0034-7094(11)70078-2","article-title":"Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting.","volume":"61","author":"Udelsmann","year":"2011","journal-title":"Rev Bras Anestesiol"},{"key":"R6-20250224","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0952-8180(91)90007-A","article-title":"Postoperative pain control with methadone following lower abdominal surgery.","volume":"3","author":"Richlin","year":"1991","journal-title":"J Clin Anesth"},{"key":"R7-20250224","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1177\/0310057X9202000109","article-title":"A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine.","volume":"20","author":"Chui","year":"1992","journal-title":"Anaesth Intensive Care"},{"key":"R8-20250224","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":"R9-20250224","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":"Gottschalk","year":"2011","journal-title":"Anesth Analg"},{"key":"R10-20250224","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1097\/ALN.0000000000000633","article-title":"Intraoperative methadone for the prevention of postoperative pain: a randomized, double-blinded clinical trial in cardiac surgical patients.","volume":"122","author":"Murphy","year":"2015","journal-title":"Anesthesiology"},{"key":"R11-20250224","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bjan.2017.09.005","article-title":"Compara\u00e7\u00e3o da analgesia p\u00f3s-operat\u00f3ria com uso de metadona versus morfina em cirurgia card\u00edaca [Comparison of postoperative analgesia with methadone versus morphine in cardiac surgery].","volume":"68","author":"Carvalho","year":"2018","journal-title":"Braz J Anesthesiol"},{"key":"R12-20250224","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/j.pain.0000000000001717","article-title":"Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis.","volume":"161","author":"D\u2019Souza","year":"2020","journal-title":"Pain"},{"key":"R13-20250224","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":"Machado","year":"2019","journal-title":"Anesth 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and sleep-disordered breathing.","volume":"31","author":"Nagappa","year":"2017","journal-title":"Best Pract Res Clin Anaesthesiol"},{"key":"R18-20250224","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/00000542-198603000-00004","article-title":"A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control.","volume":"64","author":"Gourlay","year":"1986","journal-title":"Anesthesiology"},{"issue":"1 Pt 1","key":"R19-20250224","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S0022-3476(05)81054-6","article-title":"Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children.","volume":"119","author":"Berde","year":"1991","journal-title":"J Pediatr"},{"key":"R20-20250224","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/AIA.0000000000000362","article-title":"An update on postoperative respiratory 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