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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 1, 2, 3 Christopher Geven Alexa Hollinger 4, 3, 5 Xavier Wittebole 6 Benjamin Glen Chousterman Alice Blet Etienne Gayat 7, 5 Oliver Hartmann Paul Scigalla 8 Joachim Struck 8 Andreas Bergmann Massimo Antonelli Albertus Beishuizen Jean-Michel Constantin 9, 10 Charles Damoisel 5 Nicolas Deye 11 Salvatore Di Somma Thierry Dugernier 12 Bruno François 13 Stéphane Gaudry 14, 15 Vincent Huberlant Jean-Baptiste Lascarrou 16 Gernot Marx 17 Emmanuelle Mercier 18 Haikel Oueslati 19 Peter Pickkers 20 Romain Sonneville 21 Mathieu Legrand Pierre-Francois Laterre 22 Thomas Gaillard 23 Sigismond Lasocki 24
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.

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https://hal.univ-angers.fr/hal-02616912
Contributeur : Okina Université d'Angers <>
Soumis le : lundi 25 mai 2020 - 03:36:53
Dernière modification le : mercredi 19 août 2020 - 11:21:31

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Alexandre Mebazaa, Christopher Geven, Alexa Hollinger, Xavier Wittebole, Benjamin Glen Chousterman, et al.. 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. Critical Care, 2018, 22, pp.354. ⟨10.1186/s13054-018-2243-2⟩. ⟨hal-02616912⟩

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