title: Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.
  
  
  OBJECTIVE
  To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.
  
  
  METHODS
  The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded.
  
  
  METHODS
  Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician.
  
  
  METHODS
  Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori.
  
  
  RESULTS
  Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).
  
  
  CONCLUSIONS
  Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01151865.
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, University of Queensland and Joint Health Command, Australian Defence Force, Brisbane, Australia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reade
authors.affiliation: Austin Hospital, Melbourne, Australia.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Eastwood
authors.affiliation: School of Medicine, University of Melbourne and Austin Hospital, Melbourne, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Flinders Medical Centre, Adelaide, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bersten
authors.affiliation: Toowoomba Hospital, Toowoomba, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cheung
authors.affiliation: Peninsula Health, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.affiliation: Royal North Shore Hospital of Sydney, Sydney, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Delaney
authors.affiliation: Northern Hospital, Melbourne, Australia.
authors.forename: Angaj
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Canberra Hospital, Canberra, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: van Haren
authors.affiliation: Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Nerina
authors.initials: N
authors.lastname: Harley
authors.affiliation: Christchurch Hospital, Christchurch, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Shay
authors.initials: S
authors.lastname: McGuiness
authors.affiliation: Western Hospital, Melbourne, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Mulder
authors.affiliation: Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: O'Donoghue
authors.affiliation: Geelong Hospital, Geelong, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Simpson
authors.affiliation: Wellington Hospital, Wellington, New Zealand18Medical Research Institute of New Zealand, Wellington.
authors.forename: Paul
authors.initials: P
authors.lastname: Young
mesh_terms: D000368:Aged; D001315:Australia; D000075202:Contraindications; D003693:Delirium / Q000150:complications / Q000188:drug therapy*; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D016016:Proportional Hazards Models; D011595:Psychomotor Agitation / Q000188:drug therapy*; D012121:Respiration, Artificial / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome; D015300:Ventilator Weaning
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine