• Giovanni Landoni, Marco Comis, Massimiliano Conte, Gabriele Finco, Marta Mucchetti, Gianluca Paternoster, Antonio Pisano, Laura Ruggeri, Gabriele Alvaro, Manuela Angelone, Pier C Bergonzi, Speranza Bocchino, Giovanni Borghi, Tiziana Bove, Giuseppe Buscaglia, Luca Cabrini, Lino Callegher, Fabio Caramelli, Sergio Colombo, Laura Corno, Paolo Del Sarto, Paolo Feltracco, Alessandro Forti, Marco Ganzaroli, Massimiliano Greco, Fabio Guarracino, Rosalba Lembo, Rosetta Lobreglio, Roberta Meroni, Fabrizio Monaco, Mario Musu, Giovanni Pala, Laura Pasin, Marina Pieri, Stefania Pisarra, Giuseppe Ponticelli, Agostino Roasio, Francesco Santini, Simona Silvetti, Andrea Székely, Massimo Zambon, Maria Chiara Zucchetti, Alberto Zangrillo, and Rinaldo Bellomo.
• 1Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2Cardiac and Vascular Department, Mauriziano Hospital, Turin, Italy. 3Department of Anesthesia and Intensive Care, Maria Cecilia Hospital - GVM Care & Research, Cotignola (RA), Italy. 4Department of Medical Sciences "M. Aresu," University of Cagliari, Cagliari, Italy. 5Cardiovascular Anesthesia and Intensive Care, San Carlo Hospital, Potenza, Italy. 6Division of Cardiac Anesthesia and Intensive Care, Azienda Ospedaliera Dei Colli, V Monaldi, Naples, Italy. 7A.O. Mater Domini Germaneto, Catanzaro, Italy. 8Cardioanesthesia and Intensive Care, IRCCS University Hospital San Martino Ist, Genova, Italy. 9Department of Anesthesia and Intensive Care, S. Maria dei Battuti Hospital ULSS 9, Treviso, Italy. 10Cardiothoracic and Vascular Anesthesia and Intensive Care, S. Orsola-Malpighi University Hospital, Bologna, Italy. 11FTGM-"G. Pasquinucci" Heart Hospital, Massa, Italy. 12Department of Pharmacology and Anesthesiology, University Hospital of Padova, Padova, Italy. 13Department of Anesthesia and Intensive Care, "S. Maria di Ca' Foncello," Treviso, Italy. 14Department of Anaesthesia and Critical Care Medicine, University Hospital of Pisa, Pisa, Italy. 15Anesthesia and Critical Care Medicine, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy. 16Department of Anesthesia and Intensive Care, University of Cagliari, Cagliari, Italy. 17Cardioanesthesia and Intensive Care, Civil Hospital "SS Annunziata," Sassari, Italy. 18Cardiac and Vascular Department, Casa di Cura Villa Verde, Taranto, Italy. 19Department of Anesthesia, Intensive Care Medicine, Cardinal Massaia Hospital, Asti, Italy. 20Division of Cardiac Surgery, University of Genova Medical School, Genova, Italy. 21Department of Anesthesiology and Intensive Care, Semmelweis University, Budapest, Hungary. 22Anesthesia and Resuscitation, United Company Hospital Papardo-Piemonte, Messina, Italy. 23Depa
• Crit. Care Med. 2015 Aug 1;43(8):1559-68.

ObjectivesWe aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions.Data SourcesMEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references.Study SelectionWe selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility.Data ExtractionFor all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up.Data SynthesisWe found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions.ConclusionsWe identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

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