A Brief History of Dexmedetomidine

In a departure from previous guideline recommendations for sedation, the new Pain, Agitation, and Delirium guidelines in CCM have moved away from benzodiazepines as first line sedatives.  Taking over are propofol or dexmedetomidine who now occupy the first line sedative of choice position.  While many of us in the ED are familiar with propofol and have amassed an understanding of its practical use, dexmedetomidine is equally unfamiliar.

Dexmedetomidine is a central alpha-2 agonist, similar to clonidine, but ~8 times more specific for the central alpha-2 receptor.  Physiologically, this translates into more sedation, less vasodilation and some opioid sparing effects.  While dexmedetomidine has been around since 1999, it hasn’t seen much action in the ED for a number of reasons: we use benzos first line, propofol is typically ready-made in the automatic dispensing cabinet, dexmedetomidine is still branded (ie, expensive), etc.)  However, with these new recommendations in CCM, an expiring patent in June/July of 2013 and drug shortages, dexmedetomidine will be a useful sedative to be aware of.

Similar to other short acting sedatives, the initial data with this drug was from surgical procedural sedation and post-op sedation. Though a safe study and consistent patient population, they don’t offer much by way of emergency department sedation of newly mechanically ventilated patients.  These initial trials also left silly restrictions in the package insert: max dose of 0.7mcg/kg/hr and max duration of 24 hours.  These restrictions existed not for evidence based safety concerns; rather, they simply weren’t studied beyond the above dose and duration.

More applicable data from mechanically vented patients in medical and surgical ICUs was delivered in the MEDNS and SEDCOM trials. Aside from demonstrating similar efficacy with either lorazepam or midazolam, dexmedetomidine was associated with less delirium. From a safety perspective, patients who received dexmedetomidine had a higher incidence of bradycardia. However, this difference disappeared when the bradycardia was considered to be clinically significant. The MENDS and SEDCOM trials each used dexmedetomidine for more than 24 hours (and has been studied for up to 30 days) and at doses of 0.8 mcg/kg/hr to 1.5mcg/kg/hr without excessive hypotension or bradycardia.

The real question, when it comes down to it for the emergency department, is why should one use dexmedetomidine over propofol?  Each agent is short acting, easily titratable, causes hypotension, and recommended above benzodiazepines.  Naturally, few studies have compared these two head-to-head.  What data do exist, dexmedetomidine and propofol demonstrated similar efficacy at achieving and maintaining time in target RASS. Interestingly, propofol this time was associated with more delirium. This was an interesting finding since propofol has not been linked to delirium until this trial, and could be a result of methodological deficiencies and small sample size. Still, even a cause and effect relationship between benzodiazepine use and ICU delirium has yet to be demonstrated. The data only places a strong association between benzos and delirium.

To me, it would seem that dexmedetomidine fits as an alternative to propofol in the ED. An alternative that could, and probably will be used whenever the next propofol shortage hits.  Before then, read up on dexmedetomidine.


A great review in the Annals of Pharmacotherapy from 2009that I highly recommend.

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