Critical Care (Dec 2018)

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

  • Alexandre Mebazaa,
  • Christopher Geven,
  • Alexa Hollinger,
  • Xavier Wittebole,
  • Benjamin Glen Chousterman,
  • Alice Blet,
  • Etienne Gayat,
  • Oliver Hartmann,
  • Paul Scigalla,
  • Joachim Struck,
  • Andreas Bergmann,
  • Massimo Antonelli,
  • Albertus Beishuizen,
  • Jean-Michel Constantin,
  • Charles Damoisel,
  • Nicolas Deye,
  • Salvatore Di Somma,
  • Thierry Dugernier,
  • Bruno François,
  • Stephane Gaudry,
  • Vincent Huberlant,
  • Jean-Baptiste Lascarrou,
  • Gernot Marx,
  • Emmanuelle Mercier,
  • Haikel Oueslati,
  • Peter Pickkers,
  • Romain Sonneville,
  • Matthieu Legrand,
  • Pierre-François Laterre,
  • AdrenOSS-1 study investigators

DOI
https://doi.org/10.1186/s13054-018-2243-2
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 12

Abstract

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Abstract Background Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5–148.1 pg/ml]. Initial SOFA score was 7 [IQR 5–10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9–2.9]; adjusted HR 1.6 [CI 1.1–2.5]) and between bio-ADM levels and SOFA score (p 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5–9.8). Conclusions AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

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