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.”
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