Therapy Dexmedetomidine vs Midazolam for sedation of critically ill patients
This review may be edited
Summary
Posted By:	Rosalind Elliott
E-Mail:	rmelliot@nsccahs.health.nsw.gov.au
Posted Date:	15/04/09
Title:	Dexmedetomidine vs Midazolam for sedation of critically ill patients
Authors:	Riker, R.R., Shehabi, Y., Bokesch, P. M., Ceraso, D., Wisemandle, W., Koura, F., Whitten, P., et al.
Reference:	JAMA 2009 Feb; 301(5): 489-499
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	Context: [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. Design, Setting, and Patients: 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. Interventions: Dexmedetomidine (0.2-1.4 [mu]g/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 Outcome Measures: 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.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes. 'Patients were randomized centrally using an interactive voice response system and a computer generated schedule' It is unlikely that clinicians were aware of which group the patient would be assigned to.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes Follow-up was complete
2b. Were patients analyzed in the groups to which they were randomized?
	Did not use intention to treat as 6 pts in the dex group who did not receive dexmedetomidine and 3 pts in the midaz group who did not receive midazolam were not included in the primary analysis. However a secondary analysis was performed using intention to treat and revealed similiar results.
3. Were patients, health workers, and study personnel blind to treatment?
	Yes patients, clincians and study personnel except the study pharmacist
4. Were the groups similar at the start of the trial?
	Yes
5. Aside from the experimental intervention, were the groups treated equally?
	Not specically stated however the analgesic regimen and treatment for agitation were prescribed in the study protocol.
What are the Results?
1. How large was the treatment effect?
	Absolute risk reduction for not being within target sedation level range was 2.2% , p=0.18 in favour of dexmedetomidine. 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 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)
2. How precise was the estimate of the treatment effect?
	See above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Yes, this study was conducted in sites throughout the world.
2. Were all clinically important outcomes considered?
	The authors report 30 mortality, infection rates, duration of ventilation and stay however long term PTSD measures would have been very interseting.
3. Are the likely treatment benefits worth the potential harms and costs?
	A full economic analysis was not conducted. Although a savings was achieved with regards to reduced duration of ventilation, we do not know if this compensates for other increased costs nor if the benefits observed translate to any advantages outside the ICU.
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