• Alice Blet, Benjamin Deniau, Karine Santos, Dirk P T van Lier, Feriel Azibani, Xavier Wittebole, Benjamin G Chousterman, Etienne Gayat, Oliver Hartmann, 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, LascarrouJean-BaptisteJBCentre Hospitalier Universitaire de Nantes, Nantes, France., Gernot Marx, Emmanuelle Mercier, Haikel Oueslati, Peter Pickkers, Romain Sonneville, Matthieu Legrand, Pierre-François Laterre, Alexandre Mebazaa, and AdrenOSS-1 Study Investigators.
• Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, Paris, France. alice.blet@aphp.fr.
• Crit Care. 2021 Feb 15; 25 (1): 61.

BackgroundDipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.MethodsThe aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.ResultsMedian [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.ConclusionsAdmission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

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