title: Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov #NCT01360346.
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, A.O. San Paolo - Polo Universitario, Via A. Di Rudinì, 8-20142, Milan, Italy. giovanni.mistraletti@unimi.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mistraletti
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mantovani
authors.forename: Paolo
authors.initials: P
authors.lastname: Cadringher
authors.forename: Barbara
authors.initials: B
authors.lastname: Cerri
authors.forename: Davide
authors.initials: D
authors.lastname: Corbella
authors.forename: Michele
authors.initials: M
authors.lastname: Umbrello
authors.forename: Stefania
authors.initials: S
authors.lastname: Anania
authors.forename: Elisa
authors.initials: E
authors.lastname: Andrighi
authors.forename: Serena
authors.initials: S
authors.lastname: Barello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Carlo
authors.forename: Federica
authors.initials: F
authors.lastname: Martinetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Formenti
authors.forename: Paolo
authors.initials: P
authors.lastname: Spanu
authors.forename: Gaetano
authors.initials: G
authors.lastname: Iapichino
mesh_terms: D000284:Administration, Oral; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D002985:Clinical Protocols; D003194:Computer-Assisted Instruction; D016292:Procedural Sedation / Q000009:adverse effects / Q000379:methods*; D003243:Consciousness / Q000187:drug effects*; D016638:Critical Illness; D004359:Drug Therapy, Combination; D004502:Education, Medical, Continuing; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007318:Inservice Training; D007362:Intensive Care Units; D020407:Internet; D007558:Italy; D008140:Lorazepam / Q000008:administration & dosage; D008550:Melatonin / Q000008:administration & dosage; D008874:Midazolam / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D012107:Research Design; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D006919:Hydroxyzine; D008550:Melatonin; D008140:Lorazepam; D008874:Midazolam; D015742:Propofol
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