1. 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
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Mebazaa, Alexandre, Geven, Christopher, Bergmann, Andreas, Massat, Stéphanie, Desachy, Arnaud, Fally, Marie Anne, Robin, Laurence, Cracco, Christophe, Lafon, Charles, Calvat, Sylvie, Rouleau, Stéphane, Schnell, David, Lasocki, Sigismond, Antonelli, Massimo, Fesard, Philippe, Leblanc, Damien, Bouhours, Guillaume, Chassier, Claire, Conte, Mathieu, Gaillard, Thomas, Denou, Floriane, Kerymel, Mathieu, Guyon, Marion, Loiez, Anthéa, Beishuizen, Albertus, Lebreton, Stéphanie, Meziani, Ferhat, Allam, Hayat, Chenaf, Samir, Rahmani, Hassène, Heenen, Sarah, Kummerlen, Christine, Delabranche, Xavier, Boivin, Alexandra, Clere-Jehl, Raphaël, Constantin, Jean-Michel, Rabouël, Yannick, Pottecher, Julien, Bayer, Sophie, Metzger, Catherine, Hecketsweiler, Stéphane, Ludes, Pierre Olivier, Besancenot, Hortense, Dhif, Nadia, Freys, Guy, Lessinger, Jean-Marc, Damoisel, Charles, Launoy, Anne, Ruimy, Aude, Meyer, Alain, Szozot, M., Deye, Nicolas, Gayat, Etienne, Fournier, Marie-Céline, Abroug, Sarra, Louadah, Badr, Feliot, Elodie, Voicu, Sebastian, Malissin, I., Megarbane, Bruno, Manivet, Philippe, Victori, Gardianot, Kelly, Da Silva, La Foucher, Béatrice, Pierre, Valérie, Kerdjana, Lamia, Di Somma, Salvatore, Beeken, Thomas, Goury, Antoine, Garcon, Pierre, Gaugain, Samuel, Chousterman, Benjamin Glen, Huot, Benjamin, Barthelemy, Romain, Soyer, Benjamin, Jacob, Laurent, Legrand, Matthieu, Dugernier, Thierry, Bonnet, Francine, Legall, Chloé, Oueslati, Haikel, Cupaciu, Alexandru, Sonneville, Romain, Letrou, Sophie, Bouadma, Lila, François, Bruno, Mourvillier, Bruno, Deiler, Véronique, Magalhaes, Eric, Neuville, Mathilde, Timsit, Jean-François, Radjou, Aguila, Gaudry, Stéphane, Dubief, Emeline, Messika, Jonathan, La Combe, Béatrice, Gaudry, Stephane, Roux, Damien, Berquier, Guillaume, Laissi, Mohamed, Ricard, Jean-Damien, Perbet, Sebastien, Delmas, Julie, Pascal, Julien, Cayot, Sophie, Guerin, Renaud, Hollinger, Alexa, Huberlant, Vincent, Jabaudon, Matthieu, Roszyk, Laurence, Rolhion, Christine, Bourdier, Justine, Lematte, Mathilde, Gouhier, Charlène, Verlhac, Camille, Godet, Thomas, Radji, Sophiano, Caumon, Elodie, Lascarrou, Jean-Baptiste, Thibault, Sandrine, Marx, Nikolaus, Schuerholz, Tobias, Pezechk, Jessica, Feld, Florian, Brülls, Christian, Beeker, Thorben, Simon, Tim-Philipp, Deisz, Robert, Schindler, Achim, Marx, Gernot, Meier, Bianca, Janisch, Thorsten, Hohn, Andreas, Schedler, Dirk, Wetsch, Wolfgang, Schröder, Daniel, Meier-Hellmann, Andreas, Lucht, Alexander, Henker, Robert, Römmer, Magdalena, Mercier, Emmanuelle, Meinig, Torsten, Zacharowski, Kai D., Meybohm, Patrick, Lindau, Simone, Mutlak, Haitham, Kluge, Stefan, Ringeis, Grit, Füllekrug, Birgit, Singer, Brigitte, Nierhaus, Axel, Bangert, Katrin, de Heer, Geraldine, Frings, Daniel, Fuhrmann, Valentin, Müller, Jakob, Schreiber, Jörg, Sensen, Barbara, Siedler, Stephanie, Siewecke, Annekatrin, Söffker, Gerold, Pickkers, Peter, Wichmann, Dominic, Kerinn, Mélanie, Jaschinski, Ulrich, Kreuser, Ilse, Zanquila, Marlene, Kortgen, Andreas, Bloos, Frank, Gonnert, Falk, Thomas-Rüddel, Daniel, Haucke, Anja, Kolanos, Steffi, Kohlberg, Karina Knuhr, Bloos, Petra, Schwope, Katrin, Rossella, Marino, Russo, Veronica, Simona, Santarelli, Bartoli, Christopher, Navarin, Sylvia, Bongiovanni, Cristina, Orru, Michela, Quatrocchi, Daniela, Zoccoli, Giada, Varchetta, Antonella, de Pascale, Gennaro, Vallecoccia, Maria Sole, Cutuli, Salvatore Lucio, Digravio, Valentina, Laterre, Pierre-François, Quattrochi, Daniela, D'Arrigo, Sonia, Leone, Filippo Elvino, Beishuizen, Bert, Rinket, Martin, Border, Natalie, Bos-Burgmeijer, Mariska, Braad, Astrid, Papendorp, S., Cornet, Alexander, AdrenOSS-1 study investigators, Vermeijden, J., Trof, Ronald J., van de A, Marieke, Van Wezel, Helen, Heunks, Leo, Luijten-Arts, Chantal, Hoedemaekers, Astrid, van der Hoeven, Hans, Wittebole, Xavier, Laterre, Pierre François, Roovers, Noortje, Hemelaar, Pleun, Berghe, Caroline, Dujardin, Marie-France, Renard, Suzanne, Collienne, Christine, Zapatero, Diego Castanares, Vinetti, Marco, De Schryver, Nicolas, Thirifays, Anne, Mairesse, Jacques, Petre, Hélène, Buelens, Isabelle, Henin, Pierre, Trine, Hugues, Laurent, Yves, Sébastien, Loix, Geukens, Paul, Blet, Alice, Kehl, Laurent, Vignon, Philippe, Pichon, Nicolas, Begot, Emmanuelle, Fedou, Anne-Laure, Chapellas, Catherine, Galy, Antoine, Rodier, Nicolas, Baudrillart, Ludmilla, Nouaille, Michelle, Laleu, Séverine, Mancia, Claire, Daix, Thomas, Bourzeix, Paul, Herafa, Isabelle, Duchambon, Anne-Aurore, Lascarrou, Jean Baptiste, Fiancette, Maud, Colin, Gwenhael, Hartmann, Oliver, Henry-Lagarrigue, Matthieu, Lacherade, Jean-Claude, Lebert, Christine, Martin-Levèvre, Laurent, Vinatier, Isabelle, Yehia, Aihem, Bachoumas, Konstantinos, Joret, Aurélie, Reignier, Jean, Rousseau, Cécille, Scigalla, Paul, Maquigneau, Natacha, Alcourt, Yolaine, Zinzonni, Vanessa Erragne, Deschamps, Angélique, Robert, Angelina, Simeon-Vieules, Véronique, Aubrey, Aurélie, Mabilat, Christine, Garot, Denis, Struck, Joachim, Ehrmann, Stephan, Legras, Annick, Manikikian, Jouan, Youenn, Dequin, Pierre François, Guillon, Antoine, Bodet-Contentin, Laetitia, Rouve, Emmannuelle, Salmon, Charlotte, Brick, Lysiane, Department of Anaesthesiology and Critical Care and Burn Unit, St-Louis Hospital, Service de biochimie INSERM UMR-S942, Hôpital Lariboisière-APHP, Université Paris Diderot - Paris 7 (UPD7), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques universitaires St Luc [Bruxelles], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Adrenomed AG, Service de Médecine Intensive et Réanimation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Department of Intensive Care, St-Pierre Hospital, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de réanimation médicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Radboud university [Nijmegen], Hôpital Bichat - Claude Bernard, Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Intensive care medicine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Radboud University [Nijmegen], and MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC)
- Subjects
Male ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Medical and Health Sciences ,law.invention ,Adrenomedullin ,0302 clinical medicine ,Belgium ,law ,Germany ,Medicine ,Hospital Mortality ,Prospective Studies ,Netherlands ,Outcome ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Hematology ,Middle Aged ,Prognosis ,Shock, Septic ,Intensive care unit ,3. Good health ,Hospitalization ,Intensive Care Units ,Infectious Diseases ,Italy ,Anesthesia ,outcome ,biomarker ,Female ,SOFA score ,France ,medicine.symptom ,Infection ,Multiple Organ Failure ,Sepsis ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Clinical Research ,Biomarker ,Sepsis-2 ,Sepsis-3 ,Aged ,Biomarkers ,Chi-Square Distribution ,Humans ,Length of Stay ,Patient Outcome Assessment ,Proportional Hazards Models ,Survival Analysis ,Settore MED/41 - ANESTESIOLOGIA ,AdrenOSS-1 study investigators ,Lactic Acid ,Renal replacement therapy ,business.industry ,Septic shock ,Research ,Inflammatory and immune system ,Organ dysfunction ,030208 emergency & critical care medicine ,lcsh:RC86-88.9 ,medicine.disease ,Emergency & Critical Care Medicine ,Good Health and Well Being ,Blood pressure ,business - 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. Electronic supplementary material The online version of this article (10.1186/s13054-018-2243-2) contains supplementary material, which is available to authorized users.
- Published
- 2018
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