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Table 1 Salient features of key sedation trials conducted in the last 15 years

From: Intensive care sedation: the past, present and the future

Authors (Year) Design (Number) Time to randomly assign Main inclusion Patients/intervention versus control Time on treatment Primary outcome Main results
Mehta et al. [37] (2012) Multicenter RCT open-label (423) 1 to 4 days Ventilated >48 hours Medical 80%+, DSI + PS versus PS. All patients received MDZ and received SBT. Until extubated median 7 days Time to extubation No difference in outcomes
Jakob et al. [27] (2012) Multicenter two RCTs Double-blind 48 hours of sedation Ventilated >48 hours Medical Surgical and Trauma
Dex versus MDZ and
Median 42 (23-72) hours for Dex Time at target sedation RASS −3 to 0 No difference in primary outcome. Shorter time to
  (998, 2 studies)    Dex versus Propofol. All patients DSI, SBT    extubation
Strøm et al. [14] (2010) Single-center Unblinded RCT (140 but 113 analyzed) 24 hours after intubation Ventilated >24 hours General ICU patients Morphine versus propofol (first 48 hours) then MDZ. DSI conducted in all patients Not given. Study staff intervened 2-5 days Ventilator-free days at 28 days after intubation More ventilator-free days, shorter ICU and hospital stays
Treggiari et al. [33] (2009) Single-center Open-label RCT (129) Up to 3 days Ventilated >12 hours Mainly post-surgical (80%+) Light sedation versus deep sedation using Ramsay scale Mean days Light 2.9 versus deep 5.5 Post-traumatic stress at 28 days Trend to lower post-traumatic stress
Skrobic et al. [31] (2010) Single-center Pre and post (572 and 561) 24 hours after ICU admission Admitted >24 hours Protocolized analgesia and sedation with non-pharmacologic intervention (music) Through ICU stay Sedative and analgesic needs Shorter ICU and hospital stays, less sub-syndromal delirium
Riker et al. [26] (2009) Multicenter RCT double-blind (375 at 2:1) Up to 96 hours Ventilated >24 hours Medical 85%+ Dex versus MDZ, rescue MDZ Sedation titration to RASS Median days Dex 3.5 (2-5.2) versus MDZ 4.1 (2.8-6.1) Time in target RASS −2 to +1 No difference in RASS range. Shorter ventilation time and less
     Fentanyl opioid of choice    delirium
Girard et al. [30] (2008) Multicenter RCT Unblinded (335) 2.2 to 4 days Ventilated >12 hours General ICU SAT and SBT versus usual sedation care and SBT Research personnel involved Time to pass SBT 3.8 (1-14), 3.9 (1-11) Ventilator-free days More ventilator-free days and lower 12-month risk of death
De Wit et al. [35] (2008) Single-center RCT unblinded (74) Not reported Ventilated in medical ICU Medical respiratory ICU DSI versus sedation protocol 6.7 (4-10) days Ventilation time Terminated early; higher mortality longer vent time
Bucknall et al. [32] (2008) Single-center RCT unblinded (312) Not reported Ventilated in ICU Medical/surgical/trauma
PS versus usual sedation practice
Ventilation hours 79 protocol 59 control Ventilation time No difference in outcomes
Pandharipande et al. [40] (2007) 2-center RCT double-blind (106) 48 hours after mechanical ventilation Ventilated >24 hours Medical 70%+/surgical Dex versus lorazepam Rescue propofol and fentanyl 5 (2-6) Dex versus 4 (2-6) lorazepam Delirium-free days, coma-free days Higher coma-free days but no effect on delirium
Carson et al. [25] (2006) 2-center RCT Open-label (132) over 56 months 1.5 days on average after ventilation Ventilated >48 hours + lorazepam >10 mg/hour Medical ICU patients Lorazepam boluses versus propofol infusion with DSI Not reported. Ventilation times 5.8 versus 8.4 days lorazepam Ventilation time Shorter ventilation time and ICU stay, more ventilation-free days
Kress et al. [34] (2000) Single-center RCT unblinded (128) Ventilated patients Ventilated >48 hours and sedated Medical ICU DSI started 48 hours after enrollment versus usual care. Research personnel involved Not reported. Ventilation times 4.9 versus 7.3 days Ventilation and ICU time Reduced ventilation time and ICU stay
Brook et al. [30] (1999) Single-center RCT unblinded (321) Ventilated and in ICU >24 hours Ventilated >24 hours Medical ICU patients sedated with lorazepam. Nurse-implemented PS versus usual care 3.5 (4) days in protocol versus 5.6 (6.4) days controls Ventilation time Shorter ventilation time and ICU stay
  1. Dex, dexmedetomidine; DSI, daily sedative interruption; ICU, intensive care unit; MDZ, midazolam; PS, protocolized sedation; RASS, Richmond Agitation Sedation Scale; RCT, randomized controlled trial; SAT, spontaneous awakening trial; SBT, spontaneous breathing trial.