Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients A Randomized Trial
Context γ-Aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates
that the α2 agonist dexmedetomidine may have distinct advantages.
Objective To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients.
Design, Setting, and Patients Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among
375medical/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.
Interventions Dexmedetomidine (0.2-1.4 μg/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.
Main OutcomeMeasures Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and openlabel
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 dexmedetomidinetreated
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). Dexmedetomidinetreated 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.
Trial Registration clinicaltrials.gov Identifier: NCT00216190 下载pdf全文 Title：Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients The MENDS Randomized Controlled Trial
Context Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction.
Objective To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam.
Design, Setting, Patients, and Intervention Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU).
Main Outcome Measures Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal.
Results Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P=.01) and a lower prevalence of coma (63% vs 92%; P .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P=.04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P=.18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P=.61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P=.48).
Conclusion In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion.
Trial Registration clinicaltrials.gov Identifier: NCT00095251 下载pdf全文 Title：Dexmedetomidine and the Reduction of Postoperative Delirium after Cardiac Surgery
Background: Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. Objective: The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures. Methods: Patients underwent elective cardiac surgery with a standardized
intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam.
Results: The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization.
Conclusion:The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs. (Psychosomatics 2009; 50:206 –217)
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