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/design: 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.

Discussion: 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: Clinicaltrials.gov #NCT01360346.

Figure 1

Comparison of most used ICU sedation/agitation scales highlighting the target of ‘conscious sedation’.

Figure 2

Study protocol. During the first 2 days of treatment, clinical conditions may require ‘deep sedation’ (RASS target from −4 to 0), achievable only by intravenous drugs. As soon as possible, even if critical conditions persist, the ‘conscious sedation’ period begins (RASS target −1/0). Within 24 h after meeting enrollment criteria, patients undergo a single-blind RCT lasting until ICU discharge: in the intravenous (control) arm, patients receive only i.v. drugs, according to ABC protocol [10]; in the enteral (intervention) arm, patients must interrupt i.v. sedatives within 48h, maintaining enteral ones until ICU discharge [25]. All sedatives have to be carefully tapered off to use the lowest effective dose. NGT, Naso-gastric tube; NJT, Naso-jejunal tube; RASS, Richmond Agitation Sedation Scale; RCT, Randomized controlled trial.

Figure 3

Selection criteria for high-risk critically-ill patients. Patients most representative of critical population present both high severity (SAPS higher than median) and high intensity (ventilation days higher than median) criteria. In these ICU patients, each therapeutic choice possibly influences clinical outcome [26].

Figure 4

Control arm: intravenous sedation, based on literature evidence[[2],[8]].

Figure 5

Intervention arm: enteral sedation. Local guidelines for conscious enteral sedation, adopted since 2001 in A.O. San Paolo - Polo Universitario, Milan, Italy following a multidisciplinary commission composed by intensivists, neurologists, and psychiatrists.

Figure 6

Bedside flowchart for pain management in ICU patients.

Figure 7

Bedside flowchart for sedation/agitation management in ICU patients.

Figure 8

Bedside flowchart for delirium management in ICU patients.

Figure 9

Post-pyloric access: guide-wired nasojejunal tube positioned under fluoroscopy.

Figure 10

Home pages of the two Internet websites specifically designed for the SedaEN study.http://www.sedaen.it is the website where patients are randomized and patients’ data are recorded, while http://www.sedaicu.it/en is available to all nurses and physicians 24/7, containing materials for the correct use of validated tools for neurological monitoring of critically-ill patients, both in Italian and English.

Figure 11

Number of patients admitted to the SedaEN participating ICUs from January 24 to December 31, 2012. In blue: all patients recorded on the website. In light blue: patients randomized. In light green: patients from centers included in the planned sub-analysis comparing the participating ICUs (at least 20 per center). In green: patients from centers meeting the requested number of enrolments (30 patients). ALE, A.O.N. SS. Antonio e Biagio e Cesare Arrigo, Alessandria; AST, A.O. Ospedale Cardinal Massaia, Asti; DES, A. O. Ospedale Civile di Desio (MI); HSP, A.O. San Paolo - Polo Universitario, Milano; LEG, A.O. Ospedale Civile di Legnano (MI); MOD, Nuovo Ospedale Civile Sant’Agostino Estense, Modena; MON, A.O. San Gerardo, Monza (MB); ORB, A.O.U. San Luigi Gonzaga, Orbassano (TO); POL, I.R.C.C.S. Ospedale Maggiore Policlinico, Milano; PVU e PVD, I.R.C.C.S. San Matteo, Università degli Studi di Pavia; TOR, A.O. San Giovanni Bosco, Torino.