The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial

  • Background: This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis. Methods: This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity. Results: 1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0–45.9) and 43.1 (10.1–184.0)). Conclusions: MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.

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Author:Gunnar Elke, Frank Bloos, Darius Cameron Wilson, Frank Martin Brunkhorst, Josef Briegel, Konrad Reinhart, Markus Löffler, Stefan KlugeORCiDGND, Axel Nierhaus, Ulrich Jaschinski, Onnen Mörer, Andreas Weyland, Patrick MeybohmORCiDGND
Pubmed Id:
Parent Title (English):Critical care
Publisher:BioMed Central ; Springer
Place of publication:London ; Berlin ; Heidelberg
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/03/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:SepNet Critical Care Trials Group
Release Date:2018/11/27
Tag:Biomarkers; MR-proADM; Mortality; SOFA; Sepsis; Septic shock
Issue:1, Art. 79
Page Number:12
First Page:1
Last Page:12
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0