{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:00:05Z","timestamp":1773021605615,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The patient\u2010relevant minimal important difference for opioid consumption remains undetermined, despite its frequent use as primary outcome in trials on postoperative pain management. A minimal important difference is necessary to evaluate whether significant trial results are clinically relevant. Further, it can be used as effect size to ensure that trials are powered to find clinically relevant effects. By exploring the dose\u2013response relationship between postoperative opioid consumption and opioid\u2010related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid\u2010related adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a post\u2010hoc analysis of aggregated data from two clinical trials (PANSAID NCT02571361 and DEX2TKA NCT03506789) and one observational cohort study (Pain Map NCT02340052) on pain management after total hip and knee arthroplasty. The primary outcome is the Hodges\u2013Lehmann median difference in opioid consumption between patients with no opioid\u2010related adverse effects and patients experiencing the mildest degree of one or more opioid\u2010related adverse effects (i.e., mild nausea, sedation and\/or dizziness or vomiting). Secondary outcomes include the Hodges\u2013Lehmann median difference in opioid consumption that corresponds to one point on a cumulated opioid\u2010related adverse event 0\u201310 scale. Further, we will explore the proportion of patients that experience opioid\u2010related adverse effects for consecutive opioid dose intervals of 2\u00a0mg iv morphine equivalents. Quantile regression will be used to assess any significant interactions with patient baseline characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study will hopefully bring us one step closer to determining relevant opioid reductions and thereby improve our understanding of intervention effects and planning of future trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.14175","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T05:18:24Z","timestamp":1669439904000},"page":"248-253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Minimal important difference in opioid consumption based on adverse event reduction\u2014A study protocol"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-3751","authenticated-orcid":false,"given":"Anders Peder 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University Hospital  K\u00f8ge Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels Haxholdt","family":"Lunn","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-6614","authenticated-orcid":false,"given":"Daniel","family":"H\u00e4gi\u2010Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Anaesthesiology, Research Centre of Anaesthesiology and Intensive Care Medicine N\u00e6stved\u2010Slagelse\u2010Ringsted Hospitals  Ringsted 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