What is the best drug for treatment of acute agitation in the ED?
Generally speaking we know the real answer to such questions is, “it depends...” And this is often followed by an emphatic explanation of the clinician’s beliefs based on eminence based medicine.
This study at least makes an attempt to enter some high quality evidence into the discussion.
This randomized, controlled, double blind, triple-dummy (who you callin’ dummy?) clinical trial enrolled adult patients requiring IV sedation for acute agitation in 2 ED’s. They randomized 349 patients to either:
· Group 1: Midazolam 5mg + Droperidol 5mg or
· Group 2: Droperidol 10mg or
· Group 3: Olanzapine 10mg
If patients were not adequately sedated by five minutes they could get further pre-specified study drug.
The primary outcome was adequate sedation by 10 minutes.
If you have any knowledge of pharmacodynamics of the study drugs, you can probably guess the results.
Yes, the midazolam group did better. By the 10 minute mark, about 75% were adequately sedated vs. 50% in the groups that got monotherapy with droperidol or olanzapine.
Once again, the results of this study are not a surprise. Intravenous midazolam works within seconds of IV administration whereas the antipsychotics take several minutes.
I personally (eminence based medicine anyone?) rapidly titrate midazolam in combination with a single dose of antipsychotic. I have most of this done well before the 10 minute mark with the attendants already wiping the sweat off their brow.
Of course we have made no mention of safety. This study was not powered for safety outcomes. Nevertheless it is quite clear that drugs in combination require extra care; especially benzodiazepines.
What’s the take-home point?
Combination therapy with IV midazolam plus an antipsychotic is probably the best strategy if the goal is rapid sedation of the acutely agitated patient. But really, therapy should be tailored to the individual patient and adequate precautions taken.
This is a great triple dummy RCT... but whatever you do, “don’t call me stupid.”
Taylor DM, Yap CL, Knott JC, et al. Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial. Ann Emerg Med. 2016 Oct 10. pii: S0196-0644(16)30456-5. doi: 10.1016/j.annemergmed.2016.07.033