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      Circulating bioactive adrenomedullin as a marker of sepsis, septic shock and critical illness

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          Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis.


          In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis.


          Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better.


          Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.

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          Most cited references 41

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

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              Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

              To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".

                Author and article information

                Crit Care
                Critical Care
                BioMed Central (London )
                4 November 2020
                4 November 2020
                : 24
                [1 ]GRID grid.4514.4, ISNI 0000 0001 0930 2361, Department of Clinical Medicine, Anaesthesiology and Intensive Care, , Lund University, ; 22185 Lund, Sweden
                [2 ]GRID grid.411843.b, ISNI 0000 0004 0623 9987, Department of Intensive and Perioperative Care, , Skåne University Hospital, ; 20502 Malmö, Sweden
                [3 ]Department of Anaesthesia and Intensive Care, Kristianstad Hospital, 29133 Kristianstad, Sweden
                [4 ]GRID grid.413823.f, ISNI 0000 0004 0624 046X, Department of Anaesthesia and Intensive Care, , Helsingborg Hospital, ; 25437 Helsingborg, Sweden
                [5 ]SphingoTec GmbH, 16761 Henningsdorf, Germany
                [6 ]GRID grid.411843.b, ISNI 0000 0004 0623 9987, Department of Infectious diseases, , Skåne University Hospital, ; 20502 Malmö, Sweden
                [7 ]GRID grid.411843.b, ISNI 0000 0004 0623 9987, Department of Internal medicine, , Skåne University Hospital, ; 20502 Malmö, Sweden
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                Funded by: Region Skåne
                Funded by: Biobanking and BioMolecular resources Research Infrastructurey (US)
                Funded by: Trolle-Wachtmeister Foundation for Medical Research
                Funded by: European Union Interreg programme IV A.
                Funded by: Lund University
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