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Article History

Received: 5 June 2025

Accepted: 25 September 2025

First Online: 27 October 2025

Declarations

:

: The Charité Ethics Committee approved the clinical trials (EA2/061/06, EA2/041/10) and this secondary analysis (EA1/284/22 January 2023, amended 01 August 2024). Patients or legal proxies provided written informed consent prior to their inclusion to the study.

: Patients or legal proxy were informed and consent was obtained for the anonymous publication of results. The manuscript does not contain identifiable persons´s data.

: The authors declare no competing interest related to the submitted work. Grants outside of the submitted work are reported by the following authors: JF was supported by the DFG (FI 965/9–1, FI 965/10–1) and the German Center for Cardiovascular Research, partner site Greifswald (DZHK 81Z5400153). FB (Balzer) received grants from DFG, Einstein Stiftung Berlin (Einstein Foundation Berlin), Gemeinsamer Bundesausschuss (Federal Joint Committee) and Koninklijke Philips N.V. FB (Balzer) received grants from or had contracts with BIH, Berlin University Alliance, Charité Foundation, German Federal Ministry of Education & Research, German Federal Ministry of Health, Hans Boeckler Foundation and Honda Research Institute during the last 36 months. FB received royalties or license fees from Elsevier, consulting fees from Medtronic, payments or honoraria for presentations or writings from GE and travel support from Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin and Robert-Koch-Institut. CS received grants from the German Research Society (DFG), Einstein Foundation Berlin Berlin, Federal Joint Committee, Federal Ministry of Education and Research (BMBF), Robert Koch Institute (RKI), Federal Ministry of Education and Research, the European Commission, Koninklijke Philips N.V. F. C, Dr. F. Köhler Chemie GmbH, Sintetica. CS discloses ownership of patent 15753 627.7 issued in Europe (Germany / Austria / Switzerland / Liechtenstein / France / United Kingdom / The Netherlands) as inventor, a U.S. patent PCT/EP 2015/067731 issued as inventor, a patent 3 174 588 issued in Europe (Germany /Switzerland / Liechtenstein / France / The Netherlands) as inventor, an international patent 10 2014 215 211.9 licensed, an international patent 10 2018 114 364.8 licensed, an international patent 10 2018 110 275.5 licensed, an international patent 50 2015 010 534.8 licensed, an international patent 50 2015 010 347.7 licensed, and an international patent 10 2014 215 212.7 licensed. CS discloses participation on a Data Safety Monitoring Board of Prothor and an advisory board of Lynx and Takeda Pharmaceutical Company Limited. CS discloses unpaid roles in Association of the Scientific Medical Societies in Germany AWMF), DFG review boards German National Academy of Sciences—Leopoldina, Berlin Medical Society, European Society of Intensive Care Medicine, European Society of Anaesthesiology and Intensive Care, German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive care and Emergency Medicine, German Sepsis Foundation. SB reports salaried employment at Pfizer Pharma GmbH. Pfizer had no involvement in the conception, design, execution, or interpretation of the study, nor in the preparation or decision to submit the manuscript for publication.