The Effect of Guanfacine on Delirium in the Critically Ill: A Randomized Clinical Trial

The Effect of Guanfacine on Delirium in the Critically Ill: A Randomized Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Effect of Guanfacine on Delirium in the Critically Ill: A Randomized Clinical Trial Andrew Barker, Harper Kim, Christopher A Chapleau, Tanvi Agarwal, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5200341/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This pilot study aimed to evaluate the feasibility, efficacy, and safety of guanfacine, a selective alpha-2A adrenergic receptor agonist, for reducing delirium in critically ill ICU patients. The primary objective was to determine whether guanfacine increased delirium-free days compared to placebo. Methods A single-center, randomized, double-blind, placebo-controlled trial was conducted at the University of Alabama at Birmingham (UAB) Hospital. Participants included adult ICU patients diagnosed with delirium. Patients were randomized to receive 2 mg of guanfacine or a placebo daily for up to 14 days. The primary endpoint was the number of days without delirium within the 14-day period. Secondary endpoints included ICU and hospital length of stay, duration of delirium, mechanical ventilation, and hemodynamic measures. Results The study enrolled 100 patients, with 50 in each arm. The guanfacine group had more days without delirium (3.4 ± 3.7) than placebo group (2.5 ± 3.1), with an unadjusted incidence rate ratio (IRR) of 1.3 (95% CI: 1.1–1.7; p = 0.015). After adjusting for age, delirium subtype, and other confounders, the difference was not significant. No significant differences were observed in secondary outcomes. Conclusion Guanfacine increased the number of days without delirium, although the significance diminished after adjusting for confounders. The safety profile of guanfacine was favorable, showing no significant hemodynamic differences. Funding Supported by the REINVENT Program, UAB Department of Perioperative Medicine. No external funding. Trial Registration ClinicalTrials.gov Identifier: NCT04578886 ICU delirium Guanfacine Alpha-2 agonist Delirium management Full Text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5200341","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":365059773,"identity":"003f61b3-f206-4792-8d99-40af120a3780","order_by":0,"name":"Andrew Barker","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYDACCR4gcYCBgZ+BgQ0icoBYLZINJGsxOECsFv7ZvQc/V5yxyTe+kfzs0Y0aBjm+GwkELLlzLlnyzI00y2030syNc44xGEsS0sJwI8dAsuHDYQOzGwlm0rkNDIkbCGmRv5Fj/LPhw38D4xnp30Ba6glqMbiRYybZcOOAgYFEDtiWBANCWgzvnEuzbDiTbCBx5k050C8ShjPPPMCvRe527+GbDcfsDPjb07c9zqmxkec7TsAWdCBBmvJRMApGwSgYBdgBACy3SvJubS1+AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-7154-3972","institution":"University of Alabama at Birmingham","correspondingAuthor":true,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Barker","suffix":""},{"id":365059774,"identity":"8eafad2c-4f41-40ba-ba98-4ffd2e094a82","order_by":1,"name":"Harper Kim","email":"","orcid":"","institution":"University of San Francisco","correspondingAuthor":false,"prefix":"","firstName":"Harper","middleName":"","lastName":"Kim","suffix":""},{"id":365059775,"identity":"fdd681c8-ed29-48b5-93e0-ec428ff873ac","order_by":2,"name":"Christopher A Chapleau","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"A","lastName":"Chapleau","suffix":""},{"id":365059776,"identity":"03b6826e-2595-4f06-8498-200a39146ae7","order_by":3,"name":"Tanvi Agarwal","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Tanvi","middleName":"","lastName":"Agarwal","suffix":""},{"id":365059777,"identity":"92ce203f-52ea-4cb2-9d81-83134cff2933","order_by":4,"name":"Arfa Ghani","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Arfa","middleName":"","lastName":"Ghani","suffix":""},{"id":365059778,"identity":"eae20a23-6a7a-44b7-bfe3-199ebe288db3","order_by":5,"name":"Ying Ge","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Ge","suffix":""},{"id":365059779,"identity":"4d59a3f5-cf78-458a-aa3a-fb489e65a94f","order_by":6,"name":"Will Lemon","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Will","middleName":"","lastName":"Lemon","suffix":""},{"id":365059780,"identity":"3375f6c6-711c-4165-b28a-02469b1ab903","order_by":7,"name":"Susan Vu","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Vu","suffix":""},{"id":365059781,"identity":"a129432e-0d1f-454e-978e-ef2ed61223ce","order_by":8,"name":"Jeff Szychowski","email":"","orcid":"","institution":"University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Jeff","middleName":"","lastName":"Szychowski","suffix":""},{"id":365059782,"identity":"f988e27a-3ebc-40ff-bc63-97ae90bc12f4","order_by":9,"name":"Ernestina Boateng","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Ernestina","middleName":"","lastName":"Boateng","suffix":""},{"id":365059783,"identity":"d41135f0-49aa-493f-b722-f460b2b3086b","order_by":10,"name":"Hui-Chein Kuo","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Hui-Chein","middleName":"","lastName":"Kuo","suffix":""},{"id":365059784,"identity":"d5bf64b3-f0b6-44c3-9258-cfcb64218d41","order_by":11,"name":"Ashita Tolwani","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Ashita","middleName":"","lastName":"Tolwani","suffix":""},{"id":365059785,"identity":"a27eba05-f0a7-45be-807f-2f23635b94a0","order_by":12,"name":"Brant Wagener","email":"","orcid":"","institution":"The University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Brant","middleName":"","lastName":"Wagener","suffix":""}],"badges":[],"createdAt":"2024-10-03 20:32:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5200341/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5200341/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67701401,"identity":"afa28c99-dc13-420b-99ae-c5b4a297b22f","added_by":"auto","created_at":"2024-10-28 22:08:52","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":563409,"visible":true,"origin":"","legend":"","description":"","filename":"GuanfacineDeliriumManuscriptFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5200341/v1_covered_f4a3f213-30ce-41d3-ae2a-2bc1d84e6acf.pdf"}],"financialInterests":"","formattedTitle":"The Effect of Guanfacine on Delirium in the Critically Ill: A Randomized Clinical Trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ICU delirium, Guanfacine, Alpha-2 agonist, Delirium management","lastPublishedDoi":"10.21203/rs.3.rs-5200341/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5200341/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis pilot study aimed to evaluate the feasibility, efficacy, and safety of guanfacine, a selective alpha-2A adrenergic receptor agonist, for reducing delirium in critically ill ICU patients. The primary objective was to determine whether guanfacine increased delirium-free days compared to\u003c/p\u003e\n\u003cp\u003eplacebo.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA single-center, randomized, double-blind, placebo-controlled trial was conducted at the University of Alabama at Birmingham (UAB) Hospital. Participants included adult ICU patients diagnosed with delirium. Patients were randomized to receive 2 mg of guanfacine or a placebo daily for up to 14 days. The primary endpoint was the number of days without delirium within the 14-day period. Secondary endpoints included ICU and hospital length of stay, duration of delirium, mechanical ventilation, and hemodynamic measures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study enrolled 100 patients, with 50 in each arm. The guanfacine group had more days without delirium (3.4 ± 3.7) than placebo group (2.5 ± 3.1), with an unadjusted incidence rate ratio (IRR) of 1.3 (95% CI: 1.1–1.7; p = 0.015). After adjusting for age, delirium subtype, and other confounders, the difference was not significant. No significant differences were observed in secondary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuanfacine increased the number of days without delirium, although the significance diminished after adjusting for confounders. The safety profile of guanfacine was favorable, showing no significant hemodynamic differences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by the REINVENT Program, UAB Department of Perioperative Medicine. No external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinicalTrials.gov Identifier: NCT04578886\u003c/p\u003e","manuscriptTitle":"The Effect of Guanfacine on Delirium in the Critically Ill: A Randomized Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 17:18:56","doi":"10.21203/rs.3.rs-5200341/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2d9bd08c-c211-444a-abdf-e2ab9519c700","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T22:00:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 17:18:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5200341","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5200341","identity":"rs-5200341","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}