Dexmedetomidine vs Midazolam

Dexmedetomidine vs Midazola for sedation of critically ill patients : A randomised control trial. Riker, R. et al. JAMA 301 (5) 489-99.

This prospective, double blind, multicentred RCT compared the alpha agonist dexmedotomdine against midazolam. It was designed to assess safety & efficacy. A total of 375 patients expected to be ventilated for > 24hrs were randomised to either agent targeted to a RASS score of between -2 to +1. Primary outcome measure was period of time within target range, secondary end points included delirium scores & duration of ventilation

Methodology: Dex group twice as large as midazolam (244 – to gain increased information on prolonged use in the critically ill). Extensive exclusion criteria including neurological, cardiac & hepatic disease. Imporantly the protocol didn’t include daily sedation holds – a key evidence based aspect of sedation usage in AICU.

Results : There was no difference in percentage of time within the target RASS range. 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).

Interpretation: Although there was little obvious difference between the agents as clinical sedatives (ease of use, time spent within target RASS range) the suggestion of reduced delirium is interesting. We know that benzodiazepines frequently cause delirium, and that delirium is associated with poor outcomes, and yet their use persists (because they are cheap, easy to use and cardiovascularly stable agents ?). The signal to reduced time on the ventilator doesn’t fit with the similar time spent within ICU and therefore ought to be regarded as suspicious I think. It’s a shame their protocols didn’t include sedation holds, as it’s difficult to compare their results with midazolam use in UK practise.

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