{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:43:06Z","timestamp":1772163786669,"version":"3.50.1"},"reference-count":27,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,11]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Postoperative delirium (POD) is a significant complication in digestive surgery, potentially increasing hospital stays, costs and mortality. Corticoids, such as dexamethasone and methylprednisolone, have been reported to reduce POD. However, the efficacy of hydrocortisone (HC) remains unexplored. This trial aims to evaluate HC\u2019s effectiveness in preventing POD in surgical patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A multicentre (three hospitals), randomised, blinded (patient-blinded, surgeon-blinded, anaesthesiologist-blinded and monitor-blinded), placebo-controlled trial of HC for the prevention of POD in patients undergoing digestive surgery was started in June 2024. Patients undergoing digestive surgery are randomly assigned to the HC or placebo group. The stratification factors are age, sex, disease stage and procedure type. Before skin incision, the participants in the HC group are administered 500\u2009mg HC intravenously. The participants in the placebo group are administered the same volume of saline that is indistinguishable from the HC. The primary outcome is the presence of POD from postoperative days 1 to 3, which is assessed using the Confusion Assessment Method-ICU (CAM-ICU). The secondary outcomes are changes in serum sodium levels, postoperative mortality, length of hospital stay, functional independence measures and complications within 28 days. To date, 61 patients of a planned 180 have been enrolled in the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This protocol was approved by the Nagoya University Clinical Research Review Board and was registered with the Japan Registry of Clinical Trials on 24 May 2024. The results of this trial will be disseminated through peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>jRCTs041240032.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-104994","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T06:45:14Z","timestamp":1753944314000},"page":"e104994","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrocortisone for the prevention of postoperative delirium in digestive surgery (HyPOD): study protocol for a multicentre randomised, blinded, placebo-controlled trial"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5384-220X","authenticated-orcid":false,"given":"Tsukasa","family":"Aritake","sequence":"first","affiliation":[{"name":"Department of Surgery, National Center for Geriatrics and Gerontology, Obu, Japan"},{"name":"Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yachiyo","family":"Kuwatsuka","sequence":"additional","affiliation":[{"name":"Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Center for Geriatrics and Gerontology, Obu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Shingu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tsushima City Hospital, Tsushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Ebata","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"2026020201503754000_15.7.e104994.1","doi-asserted-by":"publisher","DOI":"10.1159\/000140804"},{"key":"2026020201503754000_15.7.e104994.2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000322591","article-title":"Delirium is an important predictor of incident dementia among elderly hip fracture patients","volume":"31","author":"Krogseth","year":"2011","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2026020201503754000_15.7.e104994.3","doi-asserted-by":"publisher","DOI":"10.1097\/ana.0000000000000566"},{"key":"2026020201503754000_15.7.e104994.4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1001\/jamapsychiatry.2013.3320","article-title":"Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial","volume":"71","author":"Hatta","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2026020201503754000_15.7.e104994.5","doi-asserted-by":"crossref","first-page":"e970","DOI":"10.4088\/JCP.16m11194","article-title":"Preventive Effects of Suvorexant on Delirium: A Randomized Placebo-Controlled Trial","volume":"78","author":"Hatta","year":"2017","journal-title":"J Clin Psychiatry"},{"key":"2026020201503754000_15.7.e104994.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2000.tb03885.x"},{"key":"2026020201503754000_15.7.e104994.7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jamainternmed.2014.7779","article-title":"Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis","volume":"175","author":"Hshieh","year":"2015","journal-title":"JAMA Intern Med"},{"key":"2026020201503754000_15.7.e104994.8","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.10062"},{"key":"2026020201503754000_15.7.e104994.9","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819fca77"},{"key":"2026020201503754000_15.7.e104994.10","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.23736\/S0375-9393.17.11878-X","article-title":"Surgical stress response and the potential role of preoperative glucocorticoids on post-anesthesia care unit recovery","volume":"83","author":"Steinthorsdottir","year":"2017","journal-title":"Minerva Anestesiol"},{"key":"2026020201503754000_15.7.e104994.11","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-200208000-00006"},{"key":"2026020201503754000_15.7.e104994.12","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/anae.14406","article-title":"Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial","volume":"73","author":"Clemmesen","year":"2018","journal-title":"Anaesthesia"},{"key":"2026020201503754000_15.7.e104994.13","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/anae.15465","article-title":"Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture","volume":"76","author":"Kluger","year":"2021","journal-title":"Anaesthesia"},{"key":"2026020201503754000_15.7.e104994.14","doi-asserted-by":"crossref","DOI":"10.1186\/s13018-023-03930-2","article-title":"A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: an exploratory analysis of a randomized, placebo-controlled trial","volume":"18","author":"Huang","year":"2023","journal-title":"J Orthop Surg Res"},{"key":"2026020201503754000_15.7.e104994.15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/gerona\/glab248","article-title":"The Effect of Preoperative Methylprednisolone on Postoperative Delirium in Older Patients Undergoing Gastrointestinal Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"77","author":"Xiang","year":"2022","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2026020201503754000_15.7.e104994.16","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/aas.14057","article-title":"High-dose preoperative glucocorticoid for prevention of emergence and postoperative delirium in liver resection: A double-blinded randomized clinical trial substudy","volume":"66","author":"Awada","year":"2022","journal-title":"Acta Anaesthesiol Scand"},{"key":"2026020201503754000_15.7.e104994.17","doi-asserted-by":"crossref","first-page":"300060520961212","DOI":"10.1177\/0300060520961212","article-title":"Preoperative risk factors for delirium in patients aged \u226575 years undergoing spinal surgery: a retrospective study","volume":"48","author":"Onuma","year":"2020","journal-title":"J Int Med Res"},{"key":"2026020201503754000_15.7.e104994.18","doi-asserted-by":"crossref","first-page":"104","DOI":"10.14216\/kjco.20016","article-title":"Risk factors of elderly patients with postoperative delirium following major abdominal surgery for cancer","volume":"16","author":"Heo","year":"2020","journal-title":"Korean J Clin Oncol"},{"key":"2026020201503754000_15.7.e104994.19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1159\/000449044","article-title":"Risk Factors for Postoperative Delirium in Abdominal Surgery: A Proposal of a Postoperative Delirium Risk Score in Abdominal Surgery","volume":"34","author":"Miyagawa","year":"2017","journal-title":"Dig Surg"},{"key":"2026020201503754000_15.7.e104994.20","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1001\/jama.286.21.2703","article-title":"Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU)","volume":"286","author":"Ely","year":"2001","journal-title":"JAMA"},{"key":"2026020201503754000_15.7.e104994.21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.21.2703"},{"key":"2026020201503754000_15.7.e104994.22","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2107138"},{"key":"2026020201503754000_15.7.e104994.23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","article-title":"Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey","volume":"240","author":"Dindo","year":"2004","journal-title":"Ann Surg"},{"key":"2026020201503754000_15.7.e104994.24","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000133083.54934.ae"},{"key":"2026020201503754000_15.7.e104994.25","doi-asserted-by":"crossref","DOI":"10.2490\/prm.20240026","article-title":"Clinical and Cognitive Characteristics Associated with the Onset of Delirium in Postoperative Cardiovascular Surgery Patients Admitted to the ICU","volume":"9","author":"Sano","year":"2024","journal-title":"Prog Rehabil Med"},{"key":"2026020201503754000_15.7.e104994.26","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1001\/jama.1987.03400130103041","article-title":"Delirium (acute confusional states)","volume":"258","author":"Lipowski","year":"1987","journal-title":"JAMA"},{"key":"2026020201503754000_15.7.e104994.27","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1987.03400130103041"}],"updated-by":[{"DOI":"10.1136\/bmjopen-2025-104994corr1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000}}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-104994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:50:45Z","timestamp":1770025845000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-104994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,30]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bmjopen-2025-104994"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-104994","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.05.06.25327048","asserted-by":"object"}]},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}