Enteral versus intravenous approach for the sedation of critically ill patients: A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences

SedaEN investigators, G. Mistraletti, M. Umbrello, S. Salini, P. Cadringher, P. Formenti, D. Chiumello, C. Villa, R. Russo, S. Francesconi, F. Valdambrini, G. Bellani, A. Palo, F. Riccardi, E. Ferretti, M. Festa, A.M. Gado, M. Taverna, C. Pinna, A. BarbieroP.A. Ferrari, G. Iapichino

Research output: Contribution to journalArticlepeer-review


Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.

Original languageEnglish
Article number3
JournalCritical Care
Issue number1
Publication statusPublished - 2019


  • Hydroxyzine
  • Hypnotics and sedatives
  • Melatonin
  • Nursing education research
  • Patient care planning
  • hydroxyzine
  • lorazepam
  • melatonin
  • midazolam
  • propofol
  • adult
  • aged
  • Article
  • artificial ventilation
  • coma
  • comparative study
  • controlled study
  • critically ill patient
  • delirium
  • drug cost
  • enteral drug administration
  • extubation
  • feasibility study
  • female
  • hospital cost
  • human
  • intensive care unit
  • length of stay
  • major clinical study
  • male
  • mortality rate
  • multicenter study
  • outcome assessment
  • priority journal
  • protocol compliance
  • randomized controlled trial
  • Richmond Agitation Sedation Scale
  • sedation
  • Simplified Acute Physiology Score
  • single blind procedure
  • treatment duration


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