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 GaudryVincent Huberlant, Jean Baptiste Lascarrou, Gernot Marx, Emmanuelle Mercier, Haikel Oueslati, Peter Pickkers, Romain Sonneville, Matthieu Legrand, Pierre François Laterre, Pierre François Laterre, Caroline Berghe, Marie France Dujardin, Suzanne Renard, Christine Collienne, Diego Castanares Zapatero, Marco Vinetti, Nicolas De Schryver, Anne Thirifays, Jacques Mairesse, Hélène Petre, Isabelle Buelens, Pierre Henin, Hugues Trine, Yves Laurent, Loix Sébastien, Paul Geukens, Laurent Kehl, Philippe Vignon, Nicolas Pichon, Sonia D'Arrigo

Research output: Contribution to journalArticlepeer-review

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 < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 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.

Original languageEnglish
Article number354
JournalCritical Care
Volume22
Issue number1
DOIs
Publication statusPublished - Dec 21 2018

Keywords

  • Biomarker
  • Outcome
  • Sepsis-2
  • Sepsis-3

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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