{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:52:36Z","timestamp":1793393556213,"version":"4.5.0"},"reference-count":51,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Medical Science and Technology Foundation","award":["Grant No. B2019035"],"award-info":[{"award-number":["Grant No. B2019035"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,6,23]]},"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anaesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in patients with depression. However, the role of S-ketamine in preventing POD remains unknown. Therefore, this study aims to evaluate the effect of intraoperative prophylactic S-ketamine compared with that of dexmedetomidine on the incidence of POD in elderly patients undergoing non-cardiac thoracic surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This will be a randomised, double-blinded, placebo-controlled, positive-controlled, non-inferiority trial that enrolled patients aged 60\u201390 years undergoing thoracic surgery. The patients will be randomly allocated in a ratio of 1:1:1 to S-ketamine, dexmedetomidine or normal saline placebo groups using computer-generated randomisation with a block size of six. The primary outcome will be the incidence of POD within 4 days after surgery and this will be assessed using a 3-Minute Diagnostic Confusion Assessment Method two times per day. The severity and duration of POD, the incidence of emergence delirium, postoperative pain, quality of sleep, cognitive function, and the plasma concentrations of acetylcholine, brain-derived neurotrophic factor, tumour necrosis factor-\u03b1 and incidence of adverse events will be evaluated as secondary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been obtained from the Institutional Review Board of the Cancer Hospital and the Institute of Guangzhou Medical University (ZN202119). At the end of the trial, we commit to making a public disclosure available, regardless of the outcome. The public disclosure will include a publication in an appropriate journal and an oral presentation at academic meetings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      ChiCTR2100052750 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05242692\">NCT05242692<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-061535","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T12:17:18Z","timestamp":1659356238000},"page":"e061535","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Effects of subanaesthetic S-ketamine on postoperative delirium and cognitive function in elderly patients undergoing non-cardiac thoracic surgery: a protocol for a randomised, double-blinded, placebo-controlled and positive-controlled, non-inferiority trial (SKED trial)"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct05242692","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0436-3602","authenticated-orcid":false,"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lv","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2025121411422626000_12.8.e061535.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2017.11.087"},{"key":"2025121411422626000_12.8.e061535.2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.anclin.2015.05.007","article-title":"Postoperative delirium in the geriatric patient","volume":"33","author":"Schenning","year":"2015","journal-title":"Anesthesiol Clin"},{"key":"2025121411422626000_12.8.e061535.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2014.10.019"},{"key":"2025121411422626000_12.8.e061535.4","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3182147f6d"},{"key":"2025121411422626000_12.8.e061535.5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1001\/jamasurg.2018.5093","article-title":"Association between postoperative delirium and long-term cognitive function after major nonemergent surgery","volume":"154","author":"Austin","year":"2019","journal-title":"JAMA Surg"},{"key":"2025121411422626000_12.8.e061535.6","doi-asserted-by":"crossref","DOI":"10.1016\/j.jclinane.2020.109896","article-title":"Predicting postoperative delirium after microvascular decompression surgery with machine learning","volume":"66","author":"Wang","year":"2020","journal-title":"J Clin Anesth"},{"key":"2025121411422626000_12.8.e061535.7","first-page":"686","article-title":"Postoperative delirium and neurocognitive disorders","volume":"27","author":"Migirov","year":"2021","journal-title":"Curr Opin Crit Care"},{"key":"2025121411422626000_12.8.e061535.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60688-1"},{"key":"2025121411422626000_12.8.e061535.9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019223"},{"key":"2025121411422626000_12.8.e061535.10","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-91314-z","article-title":"Comparative effectiveness of pharmacological interventions to prevent postoperative delirium: a network meta-analysis","volume":"11","author":"Park","year":"2021","journal-title":"Sci Rep"},{"key":"2025121411422626000_12.8.e061535.11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200904-0537OC"},{"key":"2025121411422626000_12.8.e061535.12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12871-021-01532-1","article-title":"Effect of general anesthesia with thoracic paravertebral block on postoperative delirium in elderly patients undergoing thoracoscopic lobectomy: a randomized-controlled trial","volume":"22","author":"Wei","year":"2022","journal-title":"BMC Anesthesiol"},{"key":"2025121411422626000_12.8.e061535.13","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.bja.2020.06.063","article-title":"Postoperative delirium: perioperative assessment, risk reduction, and management","volume":"125","author":"Jin","year":"2020","journal-title":"Br J Anaesth"},{"key":"2025121411422626000_12.8.e061535.14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/ALN.0000000000000951","article-title":"Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial","volume":"124","author":"Djaiani","year":"2016","journal-title":"Anesthesiology"},{"key":"2025121411422626000_12.8.e061535.15","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0140-6736(16)30580-3","article-title":"Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial","volume":"388","author":"Su","year":"2016","journal-title":"Lancet"},{"key":"2025121411422626000_12.8.e061535.16","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1002\/bjs.11354","article-title":"Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery","volume":"107","author":"Li","year":"2020","journal-title":"Br J Surg"},{"key":"2025121411422626000_12.8.e061535.17","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1111\/anae.15469","article-title":"The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: a randomised, double-blind placebo-controlled trial","volume":"76","author":"van Norden","year":"2021","journal-title":"Anaesthesia"},{"key":"2025121411422626000_12.8.e061535.18","doi-asserted-by":"crossref","DOI":"10.1001\/jamasurg.2017.1505","article-title":"Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial","volume":"152","author":"Deiner","year":"2017","journal-title":"JAMA Surg"},{"key":"2025121411422626000_12.8.e061535.19","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s12630-019-01440-6","article-title":"Perioperative dexmedetomidine reduces delirium in elderly patients after non-cardiac surgery: a systematic review and meta-analysis of randomized-controlled trials","volume":"66","author":"Pan","year":"2019","journal-title":"Can J Anaesth"},{"key":"2025121411422626000_12.8.e061535.20","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bja.2018.04.046","article-title":"Efficacy of perioperative dexmedetomidine on postoperative delirium: systematic review and meta-analysis with trial sequential analysis of randomised controlled trials","volume":"121","author":"Duan","year":"2018","journal-title":"Br J Anaesth"},{"key":"2025121411422626000_12.8.e061535.21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0140-6736(20)30631-0","article-title":"Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial","volume":"396","author":"Turan","year":"2020","journal-title":"Lancet"},{"key":"2025121411422626000_12.8.e061535.22","doi-asserted-by":"crossref","DOI":"10.3389\/fpsyt.2018.00752","article-title":"The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment","volume":"9","author":"Safavynia","year":"2018","journal-title":"Front Psychiatry"},{"key":"2025121411422626000_12.8.e061535.23","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2009.05.008"},{"key":"2025121411422626000_12.8.e061535.24","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3171\/2017.4.SPINE161012","article-title":"Depression as an independent predictor of postoperative delirium in spine deformity patients undergoing elective spine surgery","volume":"27","author":"Elsamadicy","year":"2017","journal-title":"J Neurosurg Spine"},{"key":"2025121411422626000_12.8.e061535.25","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S2215-0366(14)70281-0","article-title":"Delirium and depression: inter-relationship and clinical overlap in elderly people","volume":"1","author":"O'Sullivan","year":"2014","journal-title":"Lancet Psychiatry"},{"key":"2025121411422626000_12.8.e061535.26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0140-6736(17)31467-8","article-title":"Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial","volume":"390","author":"Avidan","year":"2017","journal-title":"Lancet"},{"key":"2025121411422626000_12.8.e061535.27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jclinane.2020.110099","article-title":"Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: a phase IV multicentre randomised placebo-controlled double-blind clinical trial","volume":"68","author":"Hollinger","year":"2021","journal-title":"J Clin Anesth"},{"key":"2025121411422626000_12.8.e061535.28","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.02.033","article-title":"A new rapid-acting antidepressant","volume":"181","author":"Krystal","year":"2020","journal-title":"Cell"},{"key":"2025121411422626000_12.8.e061535.29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/00008506-200004000-00003","article-title":"S(+)-ketamine up-regulates neuronal regeneration associated proteins following glutamate injury in cultured rat hippocampal neurons","volume":"12","author":"Himmelseher","year":"2000","journal-title":"J Neurosurg Anesthesiol"},{"key":"2025121411422626000_12.8.e061535.30","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199609000-00011"},{"key":"2025121411422626000_12.8.e061535.31","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1613-3"},{"key":"2025121411422626000_12.8.e061535.32","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-021-01318-6","article-title":"Translating the immediate effects of S-ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial","volume":"11","author":"H\u00f6flich","year":"2021","journal-title":"Transl Psychiatry"},{"key":"2025121411422626000_12.8.e061535.33","doi-asserted-by":"crossref","DOI":"10.1097\/EJA.0000000000001591","article-title":"Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome: a randomised trial using nuclear magnetic resonance spectroscopy","volume":"39","author":"Nummela","year":"2022","journal-title":"Eur J Anaesthesiol"},{"key":"2025121411422626000_12.8.e061535.34","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezy301"},{"key":"2025121411422626000_12.8.e061535.35","doi-asserted-by":"publisher","DOI":"10.7326\/M14-0865"},{"key":"2025121411422626000_12.8.e061535.36","doi-asserted-by":"crossref","DOI":"10.1186\/s12888-020-02544-w","article-title":"Cross-cultural adaptation and validation of the 3D-CAM Chinese version in surgical ICU patients","volume":"20","author":"Mu","year":"2020","journal-title":"BMC Psychiatry"},{"key":"2025121411422626000_12.8.e061535.37","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.21.2703"},{"key":"2025121411422626000_12.8.e061535.38","doi-asserted-by":"publisher","DOI":"10.7326\/M13-1927"},{"key":"2025121411422626000_12.8.e061535.39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53120.x"},{"key":"2025121411422626000_12.8.e061535.40","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.665981","article-title":"Circulating neurofilament light predicts cognitive decline in patients with post-stroke subjective cognitive impairment","volume":"13","author":"Wang","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"2025121411422626000_12.8.e061535.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2007.12.005"},{"key":"2025121411422626000_12.8.e061535.42","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1001\/jamasurg.2020.4371","article-title":"Effect of cognitive prehabilitation on the incidence of postoperative delirium among older adults undergoing major noncardiac surgery: the Neurobics randomized clinical trial","volume":"156","author":"Humeidan","year":"2021","journal-title":"JAMA Surg"},{"key":"2025121411422626000_12.8.e061535.43","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.jtcvs.2017.10.077","article-title":"Hydroxyethyl starch is associated with early postoperative delirium in patients undergoing esophagectomy","volume":"155","author":"Jung","year":"2018","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2025121411422626000_12.8.e061535.44","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.athoracsur.2019.01.040","article-title":"Perioperative risk factors for postoperative delirium in patients undergoing esophagectomy","volume":"108","author":"Fuchita","year":"2019","journal-title":"Ann Thorac Surg"},{"key":"2025121411422626000_12.8.e061535.45","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jcrc.2014.09.010","article-title":"Delirium affects length of hospital stay after lung transplantation","volume":"30","author":"Smith","year":"2015","journal-title":"J Crit Care"},{"key":"2025121411422626000_12.8.e061535.46","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31818e4776"},{"key":"2025121411422626000_12.8.e061535.47","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/EJA.0000000000001382","article-title":"Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: a double-blind, randomised clinical trial","volume":"38","author":"Hu","year":"2021","journal-title":"Eur J Anaesthesiol"},{"key":"2025121411422626000_12.8.e061535.48","first-page":"589","article-title":"Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients: a randomised double-blind control trial","volume":"37","author":"Perbet","year":"2018","journal-title":"Anaesth Crit Care Pain Med"},{"key":"2025121411422626000_12.8.e061535.49","doi-asserted-by":"publisher","DOI":"10.1136\/emj.18.3.205"},{"key":"2025121411422626000_12.8.e061535.50","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezv336"},{"key":"2025121411422626000_12.8.e061535.51","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aev256"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-061535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T19:42:35Z","timestamp":1765741355000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-061535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,1]]},"published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1136\/bmjopen-2022-061535"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-061535","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}