Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial.
BACKGROUND
Gamma-aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the alpha(2) agonist dexmedetomidine may have distinct advantages.


OBJECTIVE
To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients.


METHODS
Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU.


METHODS
Dexmedetomidine (0.2-1.4 microg/kg per hour [n = 244]) or midazolam (0.02-0.1 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between -2 and +1) from enrollment until extubation or 30 days.


METHODS
Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events.


RESULTS
There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, -3.2% to 7.5%]; P = .18). The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 76.6% (n = 93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P < .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P = .01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P = .24). Dexmedetomidine-treated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P < .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P = .07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P < .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P = .02).


CONCLUSIONS
There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia.


BACKGROUND
clinicaltrials.gov Identifier: NCT00216190 Published online February 2, 2009 (doi:10.1001/jama.2009.56).
Riker
Richard R
RR
University of Vermont College of Medicine, USA. rikerr@mmc.org
Shehabi
Yahya
Y
Bokesch
Paula M
PM
Ceraso
Daniel
D
Wisemandle
Wayne
W
Koura
Firas
F
Whitten
Patrick
P
Margolis
Benjamin D
BD
Byrne
Daniel W
DW
Ely
E Wesley
EW
Rocha
Marcelo G
MG
D018806:APACHE; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D016292:Procedural Sedation / Q000379:methods; D016638:Critical Illness; D003693:Delirium / Q000453:epidemiology; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D012121:Respiration, Artificial
D000316:Adrenergic alpha-Agonists; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008874:Midazolam