Helge Røsjø1, Serge Masson2, Pietro Caironi3,4, Mats Stridsberg5, Michela Magnoli2, Geir Christensen6, Gabriella Moise7, Maria Cristina Urbano8, Luciano Gattinoni9, Antonio Pesenti10,11, Roberto Latini2, Torbjørn Omland1. 1. Division of Medicine, Akershus University Hospital, Lørenskog, Norway and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 2. Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. 3. Department of Anesthesia and Critical Care, Azienda-Ospedaliero Universitaria S. Luigi Gonzaga, Orbassano, Italy. 4. Dipartimento di Oncologia, Università degli Studi di Torino, Turin, Italy. 5. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 6. Institute for Experimental Medical Research, Ullevål and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 7. Department of Anesthesia and Critical Care, Ospedale Città di Sesto San Giovanni, Sesto San Giovanni, Italy. 8. Ospedale della Misericordia, Grosseto, Italy. 9. Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany. 10. Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. 11. Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
Abstract
OBJECTIVES:Secretoneurin directly influences cardiomyocyte calcium handling, and circulating secretoneurin levels seem to improve risk prediction in patients with myocardial dysfunction by integrating information on systemic stress, myocardial function, and renal function. Accordingly, in this study, we hypothesized that secretoneurin would improve risk prediction in patients with sepsis and especially in patients with septic shock as these patients are more hemodynamically unstable. DESIGN: Multicenter, interventional randomized clinical trial. SETTING: Multicenter, pragmatic, open-label, randomized, prospective clinical trial testing fluid administration with either 20% human albumin and crystalloids or crystalloid solutions alone in patients with severe sepsis or septic shock (The Albumin Italian Outcome Sepsis). PATIENTS OR SUBJECTS: In total, 540 patients with septic shock and 418 patients with severe sepsis. INTERVENTIONS: Either 20% human albumin and crystalloids or crystalloid solutions alone. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin on days 1, 2, and 7 after randomization and compared the prognostic value of secretoneurin for ICU and 90-day mortality with established risk indices and cardiac biomarkers in septic shock and severe sepsis. High secretoneurin levels on day 1 were associated with age and serum concentrations of lactate, bilirubin, creatinine, and N-terminal pro-B-type natriuretic peptide. Adjusting for established risk factors and cardiovascular biomarkers, secretoneurin levels on day 1 were associated with ICU (odds ratio, 2.27 [95% CI, 1.05-4.93]; p = 0.04) and 90-day mortality (2.04 [1.02-4.10]; p = 0.04) in patients with septic shock, but not severe sepsis without shock. Secretoneurin levels on day 2 were also associated with ICU (3.11 [1.34-7.20]; p = 0.008) and 90-day mortality (2.69 [1.26-5.78]; p = 0.01) in multivariate regression analyses and improved reclassification in patients with septic shock, as assessed by the net reclassification index. Randomized albumin administration did not influence the associations between secretoneurin and outcomes. CONCLUSIONS:Secretoneurin provides early and potent prognostic information in septic patients with cardiovascular instability.
RCT Entities:
OBJECTIVES:Secretoneurin directly influences cardiomyocyte calcium handling, and circulating secretoneurin levels seem to improve risk prediction in patients with myocardial dysfunction by integrating information on systemic stress, myocardial function, and renal function. Accordingly, in this study, we hypothesized that secretoneurin would improve risk prediction in patients with sepsis and especially in patients with septic shock as these patients are more hemodynamically unstable. DESIGN: Multicenter, interventional randomized clinical trial. SETTING: Multicenter, pragmatic, open-label, randomized, prospective clinical trial testing fluid administration with either 20% human albumin and crystalloids or crystalloid solutions alone in patients with severe sepsis or septic shock (The Albumin Italian Outcome Sepsis). PATIENTS OR SUBJECTS: In total, 540 patients with septic shock and 418 patients with severe sepsis. INTERVENTIONS: Either 20% human albumin and crystalloids or crystalloid solutions alone. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin on days 1, 2, and 7 after randomization and compared the prognostic value of secretoneurin for ICU and 90-day mortality with established risk indices and cardiac biomarkers in septic shock and severe sepsis. High secretoneurin levels on day 1 were associated with age and serum concentrations of lactate, bilirubin, creatinine, and N-terminal pro-B-type natriuretic peptide. Adjusting for established risk factors and cardiovascular biomarkers, secretoneurin levels on day 1 were associated with ICU (odds ratio, 2.27 [95% CI, 1.05-4.93]; p = 0.04) and 90-day mortality (2.04 [1.02-4.10]; p = 0.04) in patients with septic shock, but not severe sepsis without shock. Secretoneurin levels on day 2 were also associated with ICU (3.11 [1.34-7.20]; p = 0.008) and 90-day mortality (2.69 [1.26-5.78]; p = 0.01) in multivariate regression analyses and improved reclassification in patients with septic shock, as assessed by the net reclassification index. Randomized albumin administration did not influence the associations between secretoneurin and outcomes. CONCLUSIONS:Secretoneurin provides early and potent prognostic information in septicpatients with cardiovascular instability.