{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:58:21Z","timestamp":1778003901806,"version":"3.51.4"},"reference-count":18,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004333","name":"La Jolla Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001136","name":"Australian and New Zealand College of Anaesthetists","doi-asserted-by":"publisher","award":["24\/025"],"award-info":[{"award-number":["24\/025"]}],"id":[{"id":"10.13039\/501100001136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,3,14]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cardiac surgery is frequently associated with vasoplegia and vasopressor treatment. Both may be associated with postoperative complications and prolonged length of stay. The most frequently used vasopressor is norepinephrine. However, in a pilot, double-blind, randomised controlled trial (RCT) in cardiac surgery patients, angiotensin II was effective in maintaining blood pressure and was associated with a shorter duration of hospital stay than norepinephrine. Furthermore, hyperreninaemic patients were more sensitive to angiotensin II. These findings support the need for a larger RCT to determine whether angiotensin II is superior to norepinephrine as a first-line treatment for low blood pressure after cardiac surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will conduct a double-blind RCT comparing an infusion of either angiotensin II or norepinephrine intraoperatively and for up to 48 hours after the start of surgery. We will randomly allocate 400 cardiac surgery patients at multiple centres in two countries to either an equipotent angiotensin II or norepinephrine infusion, titrated to a mean arterial pressure of 70\u201380 mm Hg. The primary outcome will be length of hospital stay. Secondary outcomes will include a composite of renal, cardiovascular and neurological events. A subgroup analysis of patients with elevated baseline renin levels will be undertaken.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been granted by the Alfred Human Research Ethics Committee on 14 July 2023 (HREC\/97814\/Alfred-2023). Results will be published on completion of the trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>Australian and New Zealand Clinical Trials Registry: ACTRN12623000848606.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-095099","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T14:00:31Z","timestamp":1744725631000},"page":"e095099","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["A Prospective double-blind, randomised controlled trial comparing angiotensin II to norepinephrine to reduce length of hospital stay in cardiac surgery patients (the PORTHOS study protocol)"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-268X","authenticated-orcid":false,"given":"Tim G","family":"Coulson","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Perioperative Medicine, Alfred Health, Melbourne, Victoria, Australia"},{"name":"Department of Anaesthesiology and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia"},{"name":"Centre for Integrated Critical Care, The University of Melbourne Faculty of Medicine Dentistry and Health Sciences, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eldho","family":"Paul","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-5560","authenticated-orcid":false,"given":"Lachlan F","family":"Miles","sequence":"additional","affiliation":[{"name":"Centre for Integrated Critical Care, The University of Melbourne Faculty of Medicine Dentistry and Health Sciences, Melbourne, Victoria, Australia"},{"name":"Department of Anaesthesia and Pain Medicine, Austin Health, Heidelberg, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Pilcher","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Intensive Care, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana F","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Frei","sequence":"additional","affiliation":[{"name":"Wellington Regional Hospital, Newtown, Wellington, New Zealand"},{"name":"Medical Research Institute of New Zealand, Wellington, New Zealand"},{"name":"University of Otago, Dunedin, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"2025121602095554000_15.4.e095099.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atssr.2023.11.019"},{"key":"2025121602095554000_15.4.e095099.2","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-006-0036-z"},{"key":"2025121602095554000_15.4.e095099.3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.carrev.2010.10.004","article-title":"Is vasoplegic syndrome more prevalent with open-heart procedures compared with isolated on-pump CABG surgery?","volume":"12","author":"Sun","year":"2011","journal-title":"Cardiovasc Revasc Med"},{"key":"2025121602095554000_15.4.e095099.4","doi-asserted-by":"publisher","DOI":"10.1111\/jocs.15805"},{"key":"2025121602095554000_15.4.e095099.5","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1053\/j.jvca.2020.11.032","article-title":"Vasopressor Therapy in Cardiac Surgery\u2014An Experts\u2019 Consensus Statement","volume":"35","author":"Guarracino","year":"2021","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2025121602095554000_15.4.e095099.6","article-title":"Epidemiology, risk factors and outcomes of norepinephrine use in cardiac surgery with cardiopulmonary bypass: a multicentric prospective study","volume":"42","author":"Guinot","year":"2023","journal-title":"Anaesth Crit Care Pain Med"},{"key":"2025121602095554000_15.4.e095099.7","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4103\/aca.ACA_190_20","article-title":"Fluid resuscitation after cardiac surgery in the intensive care unit: A bi-national survey of clinician practice. (The FRACS-ICU clinician survey)","volume":"24","author":"Ramanan","year":"2021","journal-title":"Ann Card Anaesth"},{"key":"2025121602095554000_15.4.e095099.8","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1056\/NEJMoa1704154","article-title":"Angiotensin II for the Treatment of Vasodilatory Shock","volume":"377","author":"Khanna","year":"2017","journal-title":"N Engl J Med"},{"key":"2025121602095554000_15.4.e095099.9","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003092"},{"key":"2025121602095554000_15.4.e095099.10","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1177\/08850666231174870","article-title":"Trajectory of PaO2\/FiO2 Ratio in Shock After Angiotensin II","volume":"38","author":"Wieruszewski","year":"2023","journal-title":"J Intensiv Care Med"},{"key":"2025121602095554000_15.4.e095099.11","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/anae.15802","article-title":"A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery","volume":"77","author":"Coulson","year":"2022","journal-title":"Anaesthesia"},{"key":"2025121602095554000_15.4.e095099.12","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bja.2023.06.056","article-title":"Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial","volume":"131","author":"Coulson","year":"2023","journal-title":"Br J Anaesth"},{"key":"2025121602095554000_15.4.e095099.13","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1213\/ANE.0000000000005953","article-title":"The Association Between Angiotensin II and Renin Kinetics in Patients After Cardiac Surgery","volume":"134","author":"Meersch","year":"2022","journal-title":"Anesth Analg"},{"key":"2025121602095554000_15.4.e095099.14","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1053\/j.jvca.2020.06.072","article-title":"Predicting Acute Kidney Injury After Cardiac Surgery Using a Simpler Model","volume":"35","author":"Coulson","year":"2021","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2025121602095554000_15.4.e095099.15","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":"2025121602095554000_15.4.e095099.16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13054-023-04322-y","article-title":"An updated 'norepinephrine equivalent' score in intensive care as a marker of shock severity","volume":"27","author":"Kotani","year":"2023","journal-title":"Crit Care"},{"key":"2025121602095554000_15.4.e095099.17","doi-asserted-by":"crossref","unstructured":"Wallace S . Serious adverse event reporting in investigator\u2010initiated clinical trials - wallace - 2016. Medical Journal of Australia - Wiley Online Library. Available: https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.5694\/mja15.01007 [Accessed 9 Mar 2022].","DOI":"10.5694\/mja15.01007"},{"key":"2025121602095554000_15.4.e095099.18","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-095099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T10:10:07Z","timestamp":1765879807000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-095099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":18,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,15]]},"published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1136\/bmjopen-2024-095099"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-095099","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]}}}