Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study
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,
Jean-Baptiste Lascarrou,
Gernot Marx,
Emmanuelle Mercier,
Haikel Oueslati,
Peter Pickkers,
Romain Sonneville,
Matthieu Legrand,
Pierre-François Laterre,
Alexandre Mebazaa,
AdrenOSS-1 Study Investigators
Affiliations
Alice Blet
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Benjamin Deniau
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Karine Santos
4TEEN4 Pharmaceuticals GmbH
Dirk P. T. van Lier
Department of Intensive Care Medicine, Radboud University Medical Center
Feriel Azibani
Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris
Xavier Wittebole
Department of Critical Care Medicine, St Luc University Hospital, Université Catholique de Louvain
Benjamin G. Chousterman
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Etienne Gayat
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Oliver Hartmann
SphingoTec GmbH
Joachim Struck
SphingoTec GmbH
Andreas Bergmann
4TEEN4 Pharmaceuticals GmbH
Massimo Antonelli
Department of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS
Albertus Beishuizen
Department of Intensive Care, Medische Spectrum Twente
Jean-Michel Constantin
GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Sorbonne University
Charles Damoisel
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Nicolas Deye
Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris
Salvatore Di Somma
Sant’ Andrea Hospital
Thierry Dugernier
Clinique St Pierre
Bruno François
ICU Department, CHU Dupuytren
Stephane Gaudry
Hôpital Louis Mourier
Vincent Huberlant
Hôpital Jolimont
Jean-Baptiste Lascarrou
Centre Hospitalier Universitaire de Nantes
Gernot Marx
Klinik Für Operative Intensivmedizin Und Intermediate Care, Universitätsklinikum Der RWTH
Emmanuelle Mercier
CHU de Tours
Haikel Oueslati
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Peter Pickkers
Department of Intensive Care Medicine, Radboud University Medical Center
Romain Sonneville
Hopital Bichat Claude-Bernard
Matthieu Legrand
Department of Anesthesia and Perioperative Care, University of California San Francisco
Pierre-François Laterre
Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain
Alexandre Mebazaa
Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP–HP Nord, University of Paris
Abstract Background Dipeptidyl 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. Methods The 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. Results Median [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 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. Conclusions Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
