{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:02:33Z","timestamp":1762081353953,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Previous studies have suggested that long-term \u03b2-blocker therapy before sepsis is associated with reduced mortality. Sepsis-associated coagulopathy (SAC) remains a common complication in patients with sepsis and is associated with increased mortality. Adrenergic pathways are involved in the regulation of the coagulation system. Pre-existing long-term \u03b2-blocker therapy may have potentially beneficial effects on SAC and has yet to be well characterized. We aimed to assess the potential association between pre-existing long-term \u03b2-blocker therapy and the outcomes of patients with SAC. Materials and Methods: This study retrospectively screened the clinical data of adult patients with SAC admitted to the Intensive Care Unit (ICU) and respiratory ICU between May 2020 and October 2022. Patients with SAC who took any \u03b2-blocker for at least one year were considered pre-existing long-term \u03b2-blocker therapy. All enrolled patients were followed up for 28\u2009days or until death. Results: Among the 228 SAC patients, 48 received long-term \u03b2-blocker therapy before septic episodes. Pre-existing long-term \u03b2-blocker therapy was associated with reduced vasopressor requirements and a decreased 28-day mortality (log-rank test: p = 0.041). In particular, long-term \u03b2-blocker therapy was related to substantially lower D-dimer levels and a trend of improved activated partial thromboplastin time in patients with SAC during initial ICU admission. Multivariable regression analysis showed that long-term \u03b2-blocker therapy was significantly and independently associated with a 28-day mortality among patients with SAC (adjusted odds ratio, 0.55; 95% confidence interval, (0.32\u20130.94); p = 0.030). Conclusions: Pre-existing long-term \u03b2-blocker therapy might be associated with reduced vasopressor requirements and a decreased 28-day mortality among patients with SAC, providing evidence for the protective effect of \u03b2-blockers against SAC in managing sepsis.<\/jats:p>","DOI":"10.3390\/medicina58121843","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T04:25:26Z","timestamp":1671078326000},"page":"1843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association between Pre-Existing Long-Term \u03b2-Blocker Therapy and the Outcomes of Sepsis-Associated Coagulopathy: A Retrospective Study"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-7214","authenticated-orcid":false,"given":"Ying","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Physics, North China Electric Power University\u2013Baoding, Baoding 071003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1001\/jama.2019.5791","article-title":"Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis","volume":"321","author":"Seymour","year":"2019","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1097\/CCM.0000000000002997","article-title":"Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality","volume":"46","author":"Lyons","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100864","DOI":"10.1016\/j.blre.2021.100864","article-title":"Coagulopathy and sepsis: Pathophysiology, clinical manifestations and treatment","volume":"50","author":"Giustozzi","year":"2021","journal-title":"Blood Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"783234","DOI":"10.3389\/fmed.2022.783234","article-title":"Sepsis-Associated Coagulopathy Predicts Hospital Mortality in Critically Ill Patients With Postoperative Sepsis","volume":"9","author":"Ren","year":"2022","journal-title":"Front. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1111\/jth.14578","article-title":"Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation","volume":"17","author":"Iba","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1001\/jama.2019.5358","article-title":"Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients with Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial","volume":"321","author":"Vincent","year":"2019","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1111\/jth.14590","article-title":"Managing sepsis-associated coagulopathy remains an enigma","volume":"17","author":"Thachil","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/jth.13948","article-title":"Antithrombin concentrate use in sepsis-associated disseminated intravascular coagulation: Re-evaluation of a \u2018pendulum effect\u2019 drug using a nationwide database","volume":"16","author":"Tagami","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1001\/jama.2019.5792","article-title":"Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy: Another Negative Sepsis Trial?","volume":"321","year":"2019","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13054-019-2562-y","article-title":"The association between premorbid beta blocker exposure and mortality in sepsis-a systematic review","volume":"23","author":"Tan","year":"2019","journal-title":"Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/SHK.0000000000000879","article-title":"Non-Hemodynamic Effects of Catecholamines","volume":"48","author":"Hartmann","year":"2017","journal-title":"Shock"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00134-016-4249-z","article-title":"Catecholamines for inflammatory shock: A Jekyll-and-Hyde conundrum","volume":"42","author":"Andreis","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/S0140-6736(07)61317-8","article-title":"Catecholamine treatment for shock\u2014Equally good or bad?","volume":"370","author":"Singer","year":"2007","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40560-017-0215-2","article-title":"Sepsis-induced cardiac dysfunction and beta-adrenergic blockade therapy for sepsis","volume":"5","author":"Suzuki","year":"2017","journal-title":"J. Intensive Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jama.2013.278477","article-title":"Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: A randomized clinical trial","volume":"310","author":"Morelli","year":"2013","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1097\/CCM.0b013e31825b9509","article-title":"Previous prescription of beta-blockers is associated with reduced mortality among patients hospitalized in intensive care units for sepsis","volume":"40","author":"Macchia","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1097\/CCM.0000000000001308","article-title":"Long-Term beta-Blocker Therapy Decreases Blood Lactate Concentration in Severely Septic Patients","volume":"43","author":"Contenti","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"154916","DOI":"10.1016\/j.cyto.2019.154916","article-title":"Prognosis of beta-adrenergic blockade therapy on septic shock and sepsis: A systematic review and meta-analysis of randomized controlled studies","volume":"126","author":"Li","year":"2020","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/j.chest.2021.01.009","article-title":"Effect of Ultrashort-Acting beta-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"159","author":"Hasegawa","year":"2021","journal-title":"Chest"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jcrc.2020.11.002","article-title":"Vasopressor dose equivalence: A scoping review and suggested formula","volume":"61","author":"Goradia","year":"2021","journal-title":"J. Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1007\/s00134-020-06025-2","article-title":"Noradrenaline drives immunosuppression in sepsis: Clinical consequences","volume":"46","author":"Stolk","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/cc8026","article-title":"Bench-to-bedside review: Beta-adrenergic modulation in sepsis","volume":"13","author":"Aboab","year":"2009","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.1097\/CCM.0000000000001078","article-title":"beta1-Adrenergic Inhibition Improves Cardiac and Vascular Function in Experimental Septic Shock","volume":"43","author":"Kimmoun","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40560-021-00553-9","article-title":"Premorbid beta1-selective (but not non-selective) beta-blocker exposure reduces intensive care unit mortality among septic patients","volume":"9","author":"Kuo","year":"2021","journal-title":"J. Intensive Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1097\/CCM.0000000000005034","article-title":"Association Between Premorbid Beta-Blocker Exposure and Sepsis Outcomes-The Beta-Blockers in European and Australian\/American Septic Patients (BEAST) Study","volume":"49","author":"Tan","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1056\/NEJMra1808137","article-title":"Acute Infection and Myocardial Infarction","volume":"380","author":"Musher","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"272","DOI":"10.47102\/annals-acadmedsg.202220","article-title":"Sepsis, cardiovascular events and short-term mortality risk in critically ill patients","volume":"51","author":"Ho","year":"2022","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.thromres.2019.07.002","article-title":"Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model","volume":"181","author":"Matsubara","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_30","first-page":"VI44","article-title":"Effects of stress and beta-blockade on platelet function","volume":"84","author":"Hjemdahl","year":"1991","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1074\/jbc.275.3.1763","article-title":"alpha(2A)-adrenergic receptor stimulation potentiates calcium release in platelets by modulating cAMP levels","volume":"275","author":"Keularts","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1365-2125.1983.tb02238.x","article-title":"Increased platelet adhesion and aggregation in hypertensive patients: Effect of atenolol","volume":"16","author":"Markel","year":"1983","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1182\/blood.V58.3.514.514","article-title":"Prostacyclin and beta-adrenergic catecholamines inhibit arachidonate release and PGI2 synthesis by vascular endothelium","volume":"58","author":"Adler","year":"1981","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1097\/CCM.0b013e31828a678d","article-title":"Microvascular effects of heart rate control with esmolol in patients with septic shock: A pilot study","volume":"41","author":"Morelli","year":"2013","journal-title":"Crit. Care Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/12\/1843\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:48Z","timestamp":1760146908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/12\/1843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["medicina58121843"],"URL":"https:\/\/doi.org\/10.3390\/medicina58121843","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}