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

Crit Care. 2020 Nov 4;24(1):636. doi: 10.1186/s13054-020-03351-1.


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.

Keywords: Adrenomedullin; Bioactive adrenomedullin; Biomarkers; Critical illness; Cut-off; Sepsis; Septic shock.

Publication types

  • Observational Study

MeSH terms

  • Adrenomedullin / analysis*
  • Adrenomedullin / blood
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Critical Illness
  • Electronic Health Records / statistics & numerical data
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Organ Dysfunction Scores
  • Prognosis
  • Retrospective Studies
  • Sepsis / blood*
  • Sepsis / diagnosis
  • Shock, Septic / blood*
  • Shock, Septic / diagnosis
  • Sweden


  • Biomarkers
  • Adrenomedullin