title: Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial.
abstract: BACKGROUND
  Protocolized sedation and daily sedation interruption are 2 strategies to minimize sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay. We hypothesized that combining these strategies would augment the benefits.
  
  
  OBJECTIVE
  To compare protocolized sedation with protocolized sedation plus daily sedation interruption in critically ill patients.
  
  
  METHODS
  Randomized controlled trial of 430 critically ill, mechanically ventilated adults conducted in 16 tertiary care medical and surgical ICUs in Canada and the United States between January 2008 and July 2011.
  
  
  METHODS
  Continuous opioid and/or benzodiazepine infusions and random allocation to protocolized sedation (n = 209) (control) or to protocolized sedation plus daily sedation interruption (n = 214). Using validated scales, nurses titrated infusions to achieve light sedation. For patients receiving daily interruption, nurses resumed infusions, if indicated, at half of previous doses. Patients were assessed for delirium and for readiness for unassisted breathing.
  
  
  METHODS
  Time to successful extubation. Secondary outcomes included duration of stay, doses of sedatives and opioids, unintentional device removal, delirium, and nurse and respiratory therapist clinical workload (on a 10-point visual analog scale [VAS]).
  
  
  RESULTS
  Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = .52). Duration of ICU stay (median [IQR], 10 [5-17] days vs 10 [6-20] days; P = .36) and hospital stay (median [IQR], 20 [10-36] days vs 20 [10-48] days; P = .42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = .04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P < .001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = .007) and opiates (mean, 2.18 vs 1.79; P < .001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = .64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = .83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = .001).
  
  
  CONCLUSIONS
  For mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00675363.
authors.affiliation: Division of Critical Care, Department of Medicine and Interdepartmental Mount Sinai Hospital and University of Toronto, Toronto, Canada. geeta.mehta@utoronto.ca
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.forename: Lisa
authors.initials: L
authors.lastname: Burry
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.forename: Marilyn
authors.initials: M
authors.lastname: Steinberg
authors.forename: John
authors.initials: J
authors.lastname: Granton
authors.forename: Margaret
authors.initials: M
authors.lastname: Herridge
authors.forename: Niall
authors.initials: N
authors.lastname: Ferguson
authors.forename: John
authors.initials: J
authors.lastname: Devlin
authors.forename: Maged
authors.initials: M
authors.lastname: Tanios
authors.forename: Peter
authors.initials: P
authors.lastname: Dodek
authors.forename: Robert
authors.initials: R
authors.lastname: Fowler
authors.forename: Karen
authors.initials: K
authors.lastname: Burns
authors.forename: Michael
authors.initials: M
authors.lastname: Jacka
authors.forename: Kendiss
authors.initials: K
authors.lastname: Olafson
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Skrobik
authors.forename: Paul
authors.initials: P
authors.lastname: Hébert
authors.forename: Elham
authors.initials: E
authors.lastname: Sabri
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
mesh_terms: D000368:Aged; D060666:Airway Extubation; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D002985:Clinical Protocols; D016292:Procedural Sedation / Q000379:methods*; D016638:Critical Illness; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D001569:Benzodiazepines