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Olle Melander

Principal investigator

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

Author

  • Oscar H.M. Lundberg
  • Maria Lengquist
  • Martin Spångfors
  • Martin Annborn
  • Deborah Bergmann
  • Janin Schulte
  • Helena Levin
  • Olle Melander
  • Attila Frigyesi
  • Hans Friberg

Summary, in English

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Department/s

  • Anesthesiology and Intensive Care
  • SWECRIT
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Intensive Care Epidemiology

Publishing year

2020

Language

English

Publication/Series

Critical Care

Volume

24

Issue

1

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Anesthesiology and Intensive Care

Keywords

  • Adrenomedullin
  • Bioactive adrenomedullin
  • Biomarkers
  • Critical illness
  • Cut-off
  • Sepsis
  • Septic shock

Status

Published

Project

  • Identification and classification of sepsis in the intensive care unit

Research group

  • SWECRIT
  • Intensive Care Epidemiology

ISBN/ISSN/Other

  • ISSN: 1364-8535