title: Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study*.
abstract: OBJECTIVE
  To assess the feasibility and safety of delivering early goal-directed sedation compared with standard sedation.
  
  
  METHODS
  Pilot prospective, multicenter, randomized, controlled trial.
  
  
  METHODS
  Six ICUs.
  
  
  METHODS
  Critically ill adults mechanically ventilated for greater than 24 hours.
  
  
  METHODS
  Patients randomized to early goal-directed sedation received a dexmedetomidine-based algorithm targeted to light sedation (Richmond Agitation Sedation Score of -2 to 1). Patients randomized to standard sedation received propofol and/or midazolam-based sedation as clinically appropriate.
  
  
  RESULTS
  The main feasibility outcomes were time to randomization and proportion of Richmond Agitation Sedation Score assessments in the first 48 hours in the light and deep sedation range. Safety outcomes were delirium-free days, vasopressor and physical restraints use, and device removal. Randomization occurred within a median (interquartile range) of 1.1 hours (0.46-1.9) after intubation or ICU admission for out of ICU intubation. Patients in the early goal-directed sedation (n = 21) mean (SD) Acute Physiology and Chronic Health Evaluation II score was 20.2 (6.2) versus 18.6 (8.8; p = 0.53) in the standard sedation (n = 16). A significantly higher proportion of patients was lightly sedated on days 1, 2, and 3 (12/19 [63.2%], 19/21 [90.5%], and 18/20 [90%] vs 2/14 [14.3%], 8/15 [53.3%], and 9/15 [60%]; p = 0.005, 0.011, 0.036) and more Richmond Agitation Sedation Scale assessments between (-2 and 1), in the first 48 hours (203/307 [66%] versus (74/197 [38%]; p = 0.01) in the early goal-directed sedation versus standard sedation, respectively. Early goal-directed sedation patients received midazolam on 6 of 173 (3.5%) versus 4 of 114 (3.5%) standard sedation patient-days when dexmedetomidine was given. Propofol was given to 16 of 21 (76%) of early goal-directed sedation versus 16 of 16 (100%) of standard sedation patients (p = 0.04). Early goal-directed sedation patients had 101 of 175 (58%) versus 54 of 114 (47%; p = 0.27) delirium-free days and required significantly less physical restraints 1 (5%) versus 5 (31%; p = 0.03) than standard sedation patients. There were no differences in vasopressor use and self-extubation.
  
  
  CONCLUSIONS
  Delivery of early goal-directed sedation was feasible, appeared safe, achieved early light sedation, minimized benzodiazepines and propofol, and decreased the need for physical restraints. The findings of this pilot study justify further investigation of early goal-directed sedation.
authors.affiliation: University New South Wales, Clinical School of Medicine, Prince of Wales Hospital, Randwick, New South Wales, Australia. y.shehabi@unsw.edu.au
authors.forename: Yahya
authors.initials: Y
authors.lastname: Shehabi
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reade
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Frances
authors.initials: F
authors.lastname: Bass
authors.forename: Belinda
authors.initials: B
authors.lastname: Howe
authors.forename: Colin
authors.initials: C
authors.lastname: McArthur
authors.forename: Lynne
authors.initials: L
authors.lastname: Murray
authors.forename: Ian M
authors.initials: IM
authors.lastname: Seppelt
authors.forename: Steve
authors.initials: S
authors.lastname: Webb
authors.forename: Leonie
authors.initials: L
authors.lastname: Weisbrodt
mesh_terms: D018806:APACHE; D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000368:Aged; D060666:Airway Extubation / Q000706:statistics & numerical data; D000465:Algorithms; D001569:Benzodiazepines / Q000627:therapeutic use; D016292:Procedural Sedation / Q000379:methods*; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000628:therapy*; D003693:Delirium / Q000453:epidemiology; D020927:Dexmedetomidine / Q000627:therapeutic use*; D004363:Drug Utilization; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007362:Intensive Care Units; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D015742:Propofol / Q000627:therapeutic use; D011446:Prospective Studies; D012121:Respiration, Artificial; D012149:Restraint, Physical / Q000706:statistics & numerical data
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D020927:Dexmedetomidine; D008874:Midazolam; D015742:Propofol