Title: Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients A Randomized Trial
Context ϒ -Aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the 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.
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 − 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 JAMA. 2009;301(5):489-499
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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) 下载pdf全文 Title：REefsefaerccht of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial
Abstract
Introduction: Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients.
Methods: In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive
dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis.
Results: Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the
dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11).
Conclusions: In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results.
Trial Registration: NCT00095251.
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Title：A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit
Objective: To compare the intensive care unit costs and deermine factors influencing these costs in mechanically ventilated patients randomized to dexmedetomidine or midazolam by continuous infusion.
Design: Cost minimization analysis of a double-blind, multicenter clinical trial randomizing patients 2:1 to receive dexmedetomidine or midazolam from the institutional perspective.
Setting: Sixty-eight intensive care units in the United States, Australia, New Zealand, Brazil, and Argentina.
Patients: A total of 366 intubated intensive care unit patients anticipated to require sedation for >24 hrs. Measurements and Main Results: Intensive care unit resource use was compared within the two treatment arms, using the U.S. representative costs for these resources. The analyses characterized patient costs from start of study drug until intensive care unit discharge including costs associated with the intensive care unit stay, costs during mechanical ventilation, study drug acquisition cost, and costs of treating adverse drug reactions probably or possibly related to study drugs. Blinded to treatment group, costs were calculated using Medicare reimbursement schedules, average
IMS drug costs, expert opinion, and peer-reviewed literature. Censored lengths of intensive care unit stay and mechanical ventilation were imputed, using a nonparametric adjustment algorithm. Crude and multivariate median regressions were performed
to relate intensive care unit cost and treatment. Including drug acquisition cost, sedation with dexmedetomidine was associated with a median total intensive care unit cost savings of $9679 (confidence interval, $2314–$17,045) compared with midazolam.
The primary cost drivers were reduced costs of intensive care unit stay (median savings, $6584, 95% confidence interval, $727–$12,440) and reduced costs of mechanical ventilation (median savings, $2958, 95% confidence interval, $698–$5219).
Conclusions: Continuous sedation with dexmedetomidine results in significantly lower total intensive care unit costs compared with midazolam infusion for intensive care unit sedation, primarily due to decreased intensive care unit stay costs and reduced mechanical ventilation costs. (Crit Care Med 2010; 38: 497–503)
KEY WORDS: sedation; dexmedetomidine; midazolam; pharmacoeconomics; costs; outcomes
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