Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

Background. ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid oversedation, and would be as adequate as intravenous for awake patients, with fewer side effects and lower costs. This study compares two sedation strategies, in order to early reach and maintain the light sedation target. Methods. Multicenter, single-blind randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration >72 hours at ICU admission and predicted mortality >12% (Simplified Acute Physiology Score II >32 points) during the first 24 ICU hours. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. Primary outcome: percentage of work shifts with an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ± 1. Secondary outcomes: protocol feasibility, delirium- and coma-free days, costs of drugs, length of ICU and hospital stay, ICU, hospital, and one-year mortality. Results. 348 patients were 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: 81 (46.6%) vs 7 (4.2%), p<0.01, more self-extubations: 4 (2.4%) vs 14 (8.1%), p=0.03, a lighter sedative target (RASS = 0): 93 [71-100] vs 83 [61-100]%, p<0.01, and lower total costs for drugs: 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, Clinical Trial #NCT01360346, registered 25 March 2011, https://clinicaltrials.gov/ct2/show/NCT01360346. Registered on 25 March 2011.