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Acetaminophen is one of the most widely used adjuvants for perioperative multimodal analgesia. Previous studies showed that it can effectively alleviate postoperative pain, promote opioid sparing and exert anti-neuroinflammatory response, showing strong potential for preventing postoperative delirium. We, thus, propose to test the primary hypothesis that postoperative intravenous acetaminophen would reduce delirium over 5 postoperative days in older patients following major non-cardiac surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We propose a multicentre, randomised, placebo-controlled, parallel-group trial in patients aged&gt;65 years old scheduled for non-cardiac major surgery with general anaesthesia expected to last at least 2\u2009hours. A total of 1930 elderly patients will be enrolled and randomised at 1:1 ratio to acetaminophen or saline placebo groups, stratified by age, education level and trial site with randomsised blocking. Acetaminophen or saline will be given when the surgical suture begins at the end of surgery and, thereafter, a total of seven doses within 48\u2009hours after surgery. Our primary outcome will be the incidence of delirium, assessed two times per day, through the fifth postoperative day. Secondary and exploratory outcomes will include pain scores with movement, total opioid consumption, severity of delirium, intensive care unit and hospital lengths of stay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by the Ethics Committee of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (LY2023-239-C) and approved by each participating centre. This report follows the Consolidated Standards of Reporting Trials reporting guideline for randomised studies. The findings will be shared in academic meetings and peer-reviewed academic journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06653465\">NCT06653465<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-097079","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:39:12Z","timestamp":1747719552000},"page":"e097079","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Intravenous acetaminophen for postoperative delirium in older patients recovering from major non-cardiac surgery: a randomised-controlled study 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