Impact of oversedation prevention in ventilated critically ill patients: a randomized trial—the AWARE study
Authors:   SRLF Trial Group, de Jonghe Bernard , Aboab Jérôme , Aissaoui Nadia , Annane Djillali , Audoin Corinne , Baudel Jean-Luc , Brouard Florence , Cambonie Alexandre , Camilatto Isabelle , Chergui Karim , Das Vincent , da Silva Daniel , Devos Nicolas , Deye Nicolas , Ehrmann Stephan , Ganster Frédérique , Giraudeau Bruno , Grimaldi David , Gourdin Emmanuelle , Gros Antoine , Hamzaoui Olfa , Jacobs Frédéric , Kimmoun Antoine , Lacherade Jean-Claude , Lambermont Bernard , Laterre Pierre-François , Leger Julie , Legriel Stéphane , Liaudet Lucas , Luyt Charles-Edouard , Michel Philippe , Mira Jean-Paul , Monnet Xavier , Muller Grégoire , Piagnerelli Michael , Plantefeve Gaëtan , Reignier Jean , Ricard Jean-Damien , Vincent François , Aliane Jugurtha , Plouvier Fabienne , Mercat Alain , Abolfazl Mohebbi Amoli , Plantefeve Gaëtan , Cleophax Cédric , Chergui Karim , Carteaux Guillaume , Aboab Jérôme , Reignier Jean , Troche Gilles , Guerin Laurent , Girardie Patrick , Vivier Emmanuel , Hernu Romain , Obbee Philippe , Donetti Laurence , Jacques Thierry , Cravoisy-Popovic Aurélie , Boulain Thierry , Lu Qin , Reuter Danielle , Azoulay Elie , Clavier Hervé , Picard Walter , Robert René , Chouquer Renaud , Girault Christophe , da Silva Daniel , Merat Stéphane , Quentin Charlotte , Hicter Jean-François , Schenck Maleka , Dauriac Sandie , Desmaretz Jean-Luc , Hyvernat Hervé , Soumer Alexis , Stoclin Annabelle , Rigaud Jean-Philippe , Duguet Alexandre , Bodet-Contentin Laetitia , Au Siu-Ming , Ena Sébastien 
Published: September 2018

Abstract
Background
Although oversedation has been associated with increased morbidity in ventilated critically ill patients,
it is unclear whether prevention of oversedation improves mortality. We aimed to assess 90-day mortality in patients receiving a bundle of interventions to prevent oversedation as compared to usual care.

Methods
In this randomized multicentre trial, all adult patients requiring mechanical ventilation for more than 48 h were included. Two groups were compared: patients managed according to usual sedation practices (control), and patients receiving sedation according to an algorithm which provided a gradual multilevel response to pain, agitation, and ventilator dyssynchrony with no specific target to alter consciousness and no use of sedation scale and promoted the use of alternatives to continuous infusion of midazolam or propofol (intervention).

Results
Inclusions were stopped before reaching the planned enrolment. Between 2012 and 2014, 584 patients were included in the intervention group and 590 in the control group. Baseline characteristics were well balanced between groups. Although the use of midazolam and propofol was significantly lower in the intervention group, 90-day mortality was not significantly lower (39.4 vs. 44.2% in the control group, p = 0.09). There were no significant differences in 1-year mortality between the two groups. The time to first spontaneous breathing trial and time to successful extubation were significantly shorter in the intervention group than in the control group. These last results should be interpreted with precaution regarding the several limitations of the trial including the early termination.

Conclusions
This underpowered study of severely ill patients was unable to show that a strategy to prevent oversedation could significantly reduce mortality.
Trial registration NCT01617265