Alice Blet1,2,3, Benjamin Deniau4,5, Karine Santos6, Dirk P T van Lier7,8, Feriel Azibani5, Xavier Wittebole9, Benjamin G Chousterman4,5, Etienne Gayat4,5, Oliver Hartmann10, Joachim Struck10, Andreas Bergmann6, Massimo Antonelli11, Albertus Beishuizen12, Jean-Michel Constantin13, Charles Damoisel4, Nicolas Deye5,14, Salvatore Di Somma15, Thierry Dugernier16, Bruno François17,18, Stephane Gaudry19, Vincent Huberlant20, Jean-Baptiste Lascarrou21, Gernot Marx22, Emmanuelle Mercier23, Haikel Oueslati4, Peter Pickkers7,8, Romain Sonneville24, Matthieu Legrand25, Pierre-François Laterre26, Alexandre Mebazaa4,5. 1. 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. 2. Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, 2 rue Ambroise Paré, 75010, Paris, France. alice.blet@aphp.fr. 3. University of Ottawa Heart Institute and University of Ottawa, Ottawa, ON, Canada. alice.blet@aphp.fr. 4. Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, Paris, France. 5. Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, 2 rue Ambroise Paré, 75010, Paris, France. 6. 4TEEN4 Pharmaceuticals GmbH, Hennigsdorf, Germany. 7. Department of Intensive Care Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, Nijmegen, The Netherlands. 8. Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. 9. Department of Critical Care Medicine, St Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium. 10. SphingoTec GmbH, Hennigsdorf, Germany. 11. Department of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 12. Department of Intensive Care, Medische Spectrum Twente, Enschede, The Netherlands. 13. GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 14. Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Federation of Toxicology APHP, Paris-Diderot University, Paris, France. 15. Sant' Andrea Hospital, Rome, Italy. 16. Clinique St Pierre, Ottignies, Belgium. 17. ICU Department, CHU Dupuytren, Limoges, France. 18. INSERM CIC 1435/UMR 1092, Limoges, France. 19. Hôpital Louis Mourier, Colombes, France. 20. Hôpital Jolimont, Haine-St-Paul, Belgium. 21. Centre Hospitalier Universitaire de Nantes, Nantes, France. 22. Klinik Für Operative Intensivmedizin Und Intermediate Care, Universitätsklinikum Der RWTH, Aachen, Germany. 23. CHU de Tours, Tours, France. 24. Hopital Bichat Claude-Bernard, Paris, France. 25. Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, USA. 26. Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium.
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 < 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. CONCLUSIONS: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
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 shockpatients. 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 < 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. CONCLUSIONS: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
Entities:
Keywords:
Biomarker; DPP3; Organ dysfunction; Outcome; Sepsis; Septic shock