title: Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption.
abstract: Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation.
  
  
  
  This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation.
  
  
  
  Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI -0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT.
  
  
  
  Patients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation.
  
  
  
  ClinicalTrials.gov NCT00675363 . Registered 7 May 2008.
authors.affiliation: Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada. Geeta.mehta@utoronto.ca.|Mount Sinai Hospital, Suite 18-216, 600 University Ave., Toronto, M5G 1X5, Canada. Geeta.mehta@utoronto.ca.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
authors.affiliation: Department of Pharmacy and Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Burry
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ranjeeta
authors.initials: R
authors.lastname: Mallick
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Katsios
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.affiliation: Division of Critical Care Medicine and Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dodek
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Critical Care, St. Michael's Hospital, Toronto, Ontario, Canada.|Li Ka Shing Institute, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Burns
authors.affiliation: Department of Medicine and Interdepartmental Division of Critical Care Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Herridge
authors.affiliation: School of Pharmacy, Northeastern University, Boston, Massachusetts, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.affiliation: Department of Medicine, Long Beach Memorial Medical Center, Long Beach, California, USA.
authors.forename: Maged
authors.initials: M
authors.lastname: Tanios
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.|Departments of Medicine and Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Fowler
authors.affiliation: Department of Anesthesiology, University of Alberta Hospitals, Edmonton, Alberta, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Jacka
authors.affiliation: Department of Medicine, Hôpital Royal Victoria, Montréal, Quebec, Canada.
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Skrobik
authors.affiliation: Section of Critical Care, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kendiss
authors.initials: K
authors.lastname: Olafson
authors.affiliation: Departments of Medicine, Clinical Epidemiology & Biostatistics, McMaster University, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
mesh_terms: D000368:Aged; D002940:Circadian Rhythm / Q000187:drug effects*; D002985:Clinical Protocols / Q000592:standards; D054810:Deep Sedation / Q000379:methods* / Q000451:nursing; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use; D007362:Intensive Care Units / Q000458:organization & administration; D016015:Logistic Models; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America; D012121:Respiration, Artificial / Q000379:methods*
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam; D005283:Fentanyl
keywords: Diurnal rhythm; Intensive care unit; Mechanical ventilation; Opioids; Protocols; Sedation; Weaning