{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:57:30Z","timestamp":1767193050487,"version":"3.48.0"},"reference-count":49,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["grant number 82371292"],"award-info":[{"award-number":["grant number 82371292"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,18]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Prolonged infusion of anaesthetics is associated with delayed emergence (DE) from general anaesthesia due to residual drug effects. Remimazolam besylate, a novel ultrashort-acting benzodiazepine, exhibits minimal accumulation, and its sedative effects can be reversed with flumazenil. This study aimed to evaluate the incidence of DE from anaesthesia using remimazolam\u2013flumazenil or propofol in patients undergoing major spine surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This multicentre, randomised controlled trial will be conducted in five hospitals in Hunan Province, China. Approximately 164 patients undergoing major spine surgery lasting &gt;3\u2009hours will be randomly assigned to two groups in a 1:1 ratio. In the remimazolam\u2013flumazenil group, remimazolam will be administered for anaesthesia induction and maintenance, followed by flumazenil for reversal after surgery, whereas propofol will be administered in the propofol group. The primary outcome is the incidence of DE from anaesthesia. The secondary outcomes include the time to obey verbal command, time to bispectral index over 80, time to extubation, length of stay in the post-anaesthesia care unit (PACU), Richmond Agitation\u2013Sedation Scale scores and Modified Aldrete scores on arrival at PACU, at 30\u2009and 60\u2009min, as well as adverse events throughout recovery. All statistical tests will be conducted using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). A\n                      <jats:italic>P<\/jats:italic>\n                      -value&lt;0.05\u2009will be considered significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This randomised controlled trial protocol has received ethical approval from the Second Xiangya Hospital, Central South University (Approval number: LYEC2024-0357). All participants will be required to provide written informed consent before study enrolment. The findings will be disseminated at academic conferences and published in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2400092451<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-097541","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:25:25Z","timestamp":1754648725000},"page":"e097541","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of remimazolam\u2013flumazenil versus propofol on delayed emergence from anaesthesia in major spine surgery: protocol for a multicentre, single-blinded, randomised controlled trial"],"prefix":"10.1136","volume":"15","author":[{"given":"Jingjing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Anesthesiology Research Institute, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Anesthesiology Research Institute, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Anesthesiology Research Institute, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanying","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Anesthesiology Research Institute, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-6698","authenticated-orcid":false,"given":"Ruping","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Anesthesiology Research Institute, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"2025123106455199000_15.8.e097541.1","doi-asserted-by":"crossref","DOI":"10.3389\/fnsys.2014.00146","article-title":"Emergence from general anesthesia and the sleep-manifold","volume":"8","author":"Hight","year":"2014","journal-title":"Front Syst Neurosci"},{"key":"2025123106455199000_15.8.e097541.2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/0310057X8701500209","article-title":"Anaesthetic-related recovery room complications","volume":"15","author":"Zelcer","year":"1987","journal-title":"Anaesth Intensive Care"},{"key":"2025123106455199000_15.8.e097541.3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jclinane.2015.03.023","article-title":"Delayed emergence after anesthesia","volume":"27","author":"Tzabazis","year":"2015","journal-title":"J Clin Anesth"},{"key":"2025123106455199000_15.8.e097541.4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.15406\/jaccoa.2023.15.00546","article-title":"Risk factors related to delayed post-anesthetic awakening in the elderly operated by elective video laparoscopic surgery","volume":"15","author":"Castillo","year":"2023","journal-title":"JACCOA"},{"key":"2025123106455199000_15.8.e097541.5","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0672-3"},{"key":"2025123106455199000_15.8.e097541.6","first-page":"513","article-title":"Propofol. 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