Giovanni Landoni1, Vladimir V Lomivorotov1, Gabriele Alvaro1, Rosetta Lobreglio1, Antonio Pisano1, Fabio Guarracino1, Maria G Calabrò1, Evgeny V Grigoryev1, Valery V Likhvantsev1, Marcello F Salgado-Filho1, Alessandro Bianchi1, Vadim V Pasyuga1, Massimo Baiocchi1, Federico Pappalardo1, Fabrizio Monaco1, Vladimir A Boboshko1, Marat N Abubakirov1, Bruno Amantea1, Rosalba Lembo1, Luca Brazzi1, Luigi Verniero1, Pietro Bertini1, Anna M Scandroglio1, Tiziana Bove1, Alessandro Belletti1, Maria G Michienzi1, Dmitriy L Shukevich1, Tatiana S Zabelina1, Rinaldo Bellomo1, Alberto Zangrillo1. 1. From the Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute (G.L., M.G.C., F.P., F.M., R. Lembo, A.M.S., T.B., A. Belletti, A.Z.), and Vita-Salute San Raffaele University (G.L., A.Z.), Milan, the Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Mater Domini Germaneto, Catanzaro (G.A., B.A., M.G.M.), the Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza (R. Lobreglio, L.B.), the Department of Cardiovascular Anesthesia and Intensive Care, Azienda Ospedaliera Ordine Mauriziano (A. Bianchi), and the Department of Surgical Sciences, University of Turin (L.B.), Turin, the Division of Cardiac Anesthesia and Intensive Care Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli-Monaldi Hospital, Naples (A.P., L.V.), Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, the Department of Anesthesia and Critical Care Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa (F.G., P.B.), and the Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, University Hospital Policlinico S. Orsola, Bologna (M.B.) - all in Italy; the Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk (V.V. Lomivorotov, V.A.B., M.N.A.), the Department of Anesthesiology and Intensive Care, State Research Institute for Complex Issues of Cardiovascular Disease, Kemerovo (E.V.G., D.L.S.), the Department of Anesthesiology and Intensive Care, Moscow Regional Clinical and Research Institute, Moscow (V.V. Likhvantsev, T.S.Z.), and the Department of Anesthesiology and Intensive Care, Federal Center for Cardiovascular Surgery Astrakhan, Astrakhan (V.V.P.) - all in Russia; Federal University of Juiz de Fora, Juiz de Fora, Brazil (M.F.S.-F.); and the University of Melbourne, Melbourne, VIC, Australia (R.B.).
Abstract
BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).
RCT Entities:
BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).
Authors: Julia Schumann; Eva C Henrich; Hellen Strobl; Roland Prondzinsky; Sophie Weiche; Holger Thiele; Karl Werdan; Stefan Frantz; Susanne Unverzagt Journal: Cochrane Database Syst Rev Date: 2018-01-29