{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:01Z","timestamp":1791438841001,"version":"4.3.3"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF22OC0079649"],"award-info":[{"award-number":["NNF22OC0079649"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","award":["2023\u201012401"],"award-info":[{"award-number":["2023\u201012401"]}],"id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intensive care unit (ICU) delirium is a multifactorial acute brain dysfunction associated with prolonged hospitalization, increased morbidity and mortality, and higher healthcare costs. Despite these substantial negative impacts of delirium, the optimal prevention and treatment strategies are unclear. Olanzapine, an atypical antipsychotic drug, is commonly used for delirium management. We will perform an updated systematic review and meta\u2010analysis to assess the benefits and harms of olanzapine for the prevention and treatment of ICU delirium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This protocol is developed in accordance with the recommendations of The Cochrane Collaboration and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analysis Protocols (PRISMA\u2010P) guidelines. We will include all randomized clinical trials (RCTs) evaluating prophylactic or therapeutic olanzapine versus any comparator, including pharmacological, non\u2010pharmacological, placebo, or routine care\/no specific delirium\u2010directed intervention (treated as a single comparator) in ICU patients. Observational studies will be included solely to address potential harms. We will systematically search the following databases: Embase, MEDLINE, The Cochrane Library, Web of Science, CINAHL, Scopus, and PsycINFO, as well as clinical trial registries. We will perform meta\u2010analysis and trial sequential analysis (TSA) to investigate the risk of both Type I and II errors. We will assess the risk of bias using the Cochrane Risk of Bias tool (RoB\u20102). The quality of trials will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The review is registered in the PROSPERO database (CRD420261474813).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>The primary outcome is days alive and out of the hospital. The secondary outcomes include all\u2010cause mortality at 90\u2009days, number of CAM\u2010ICU (Confusion Assessment Method for the Intensive Care Unit) negative days at 30\u2009days, number of days without pharmacological treatment for delirium other than study drug during the intervention period and serious intervention\u2010related harms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This protocol outlines the methodology we will use in a systematic review with meta\u2010analysis designed to evaluate the beneficial and harmful effects of olanzapine for prevention and treatment of delirium in ICU patients. The findings of the systematic review will be disseminated through peer\u2010reviewed publication. We hope this review will inform future RCTs and improve clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aas.70352","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:24:52Z","timestamp":1791437092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olanzapine for the Prevention and Treatment of\n                    <scp>ICU<\/scp>\n                    Delirium: Protocol for a Systematic Review With Meta\u2010Analysis"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3673-5770","authenticated-orcid":false,"given":"Benedikte","family":"Liebetrau","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"},{"name":"Department of Cardiology, the Heart Centre Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4100-1144","authenticated-orcid":false,"given":"Andreas Ruhvald","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Anesthesiology and Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-4269","authenticated-orcid":false,"given":"S\u00f6ren","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Biodemography, Department of Public Health University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0981-0723","authenticated-orcid":false,"given":"Markus Harboe","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Neuroanesthesiology, The Neuroscience Centre Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-7189","authenticated-orcid":false,"given":"Sebastian","family":"Wiberg","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Anesthesiology and Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2778-8075","authenticated-orcid":false,"given":"Simon","family":"M\u00f8lstr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"},{"name":"Department of Cardiothoracic Anesthesiology and Intensive Care Copenhagen University Hospital\u2014Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM\u20105)","author":"American Psychiatric Association","year":"2013"},{"issue":"2","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-024562","article-title":"Pharmacological Interventions for Prevention and Management of Delirium in Intensive Care Patients: A Systematic Overview of Reviews and Meta\u2010Analyses","volume":"9","author":"Barbateskovic M.","year":"2019","journal-title":"BMJ Open"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.h2538","article-title":"Outcome of Delirium in Critically Ill Patients: Systematic Review and Meta\u2010Analysis","volume":"350","author":"Salluh J. 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