Open Access Highly Accessed Open Badges Study protocol

Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial

Giovanni Mistraletti1*, Elena S Mantovani1, Paolo Cadringher2, Barbara Cerri1, Davide Corbella3, Michele Umbrello1, Stefania Anania1, Elisa Andrighi1, Serena Barello1, Alessandra Di Carlo1, Federica Martinetti1, Paolo Formenti1, Paolo Spanu1, Gaetano Iapichino1 and for the SedaEN investigators

Author Affiliations

1 Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, A.O. San Paolo - Polo Universitario, Via A. Di Rudinì, Milan, 8-20142, Italy

2 Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, I.R.C.C.S Ospedale Maggiore Policlinico, Milan, Italy

3 Dipartimento di Anestesia e Rianimazione, Ospedali Riuniti di Bergamo, Bergamo, Italy

For all author emails, please log on.

Trials 2013, 14:92  doi:10.1186/1745-6215-14-92

Published: 3 April 2013



A relevant innovation about sedation of long-term Intensive Care Unit (ICU) patients is the ‘conscious target’: patients should be awake even during the critical phases of illness. Enteral sedative administration is nowadays unusual, even though the gastrointestinal tract works soon after ICU admission. The enteral approach cannot produce deep sedation; however, it is as adequate as the intravenous one, if the target is to keep patients awake and adapted to the environment, and has fewer side effects and lower costs.


A randomized, controlled, multicenter, single-blind trial comparing enteral and intravenous sedative treatments has been done in 12 Italian ICUs. The main objective was to achieve and maintain the desired sedation level: observed RASS = target RASS ± 1. Three hundred high-risk patients were planned to be randomly assigned to receive either intravenous propofol/midazolam or enteral melatonin/hydroxyzine/lorazepam. Group assignment occurred through online minimization process, in order to balance variables potentially influencing the outcomes (age, sex, SAPS II, type of admission, kidney failure, chronic obstructive pulmonary disease, sepsis) between groups. Once per shift, the staff recorded neurological monitoring using validated tools. Three flowcharts for pain, sedation, and delirium have been proposed; they have been designed to treat potentially correctable factors first, and, only once excluded, to administer neuroactive drugs. The study lasted from January 24 to December 31, 2012. A total of 348 patients have been randomized, through a centralized website, using a specific software expressly designed for this study. The created network of ICUs included a mix of both university and non-university hospitals, with different experience in managing enteral sedation. A dedicated free-access website was also created, in both Italian and English, for continuous education of ICU staff through CME courses.


This ‘educational research’ project aims both to compare two sedative strategies and to highlight the need for a profound cultural change, improving outcomes by keeping critically-ill patients awake.

Trial registration number #NCT01360346

Sedation; Hydroxyzine; Melatonin; Enteral approach; High-risk critically ill; Educational research