{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:58:09Z","timestamp":1779328689504,"version":"3.51.4"},"reference-count":22,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"unspecified","delay-in-days":20,"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":[[2022,1,5]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) after non-cardiac surgery is a strong predictor for cardiovascular complications and reflects increased myocardial strain. NT-pro-BNP concentrations significantly rise after non-cardiac surgery within the first 3 days. Levosimendan is a potent inotropic drug that increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days. Thus, we will test the effect of a pre-emptive perioperative administration of levosimendan on postoperative NT-pro-BNP concentration as compared with the administration of a placebo in patients undergoing moderate-risk to high-risk major abdominal 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-blinded prospective randomised trial at the Medical University of Vienna, Vienna, Austria (and potentially a second centre in Germany), including 230 patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients will be randomly assigned to receive a single dose of 12.5 mg levosimendan versus placebo after induction of anaesthesia. The primary outcome will be the postoperative maximum NT-pro-BNP concentration between both group within the first three postoperative days. Our secondary outcomes will be the incidence of myocardial ischaemia, myocardial injury after non-cardiac surgery and a composite of myocardial infarction and death within 30 days and 1 year after surgery between both groups. Our further secondary outcome will be stratification of NT-pro-BNP values according to previously thresholds to predict mortality of myocardial infarction after surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study was approved by the Ethics Committee of the Medical University of Vienna on 14 July 2020 (EK 2187\/2019). Written informed consent will be obtained from all patients a day before surgery. Results of this study will be submitted for publication in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04329624\">NCT04329624<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-058216","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T10:26:37Z","timestamp":1642760797000},"page":"e058216","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of perioperative levosimendan administration on postoperative N-terminal pro-B-type natriuretic peptide concentration in patients with increased cardiovascular risk factors undergoing non-cardiac surgery: protocol for the double-blind, randomised, placebo-controlled IMPROVE trial"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04329624","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04329624","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-6038","authenticated-orcid":false,"given":"Christian","family":"Reiterer","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Outcome Research Consortium, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Kabon","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Taschner","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolas","family":"Adamowitsch","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Graf","sequence":"additional","affiliation":[{"name":"Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Fraunschiel","sequence":"additional","affiliation":[{"name":"ITSC - IT Systems & Communications, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Kuhrn","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Clement","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Treskatsch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charite Universitatsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charite Universitatsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Fleischmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Outcome Research Consortium, Cleveland, Ohio, USA"},{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"2025121605152736000_12.1.e058216.1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31829083f1"},{"key":"2025121605152736000_12.1.e058216.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.64"},{"key":"2025121605152736000_12.1.e058216.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.04.004"},{"key":"2025121605152736000_12.1.e058216.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.08.1630"},{"key":"2025121605152736000_12.1.e058216.5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.4360"},{"key":"2025121605152736000_12.1.e058216.6","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-020-04336-9","article-title":"The effect of supplemental oxygen on perioperative brain natriuretic peptide concentration in cardiac risk patients - 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