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Best knock-down for agitated patients

November 24, 2016

Short Attention Span Summary

One, two, three drugs you’re out…
This was a rock solid, well executed RCT that found midazolam 5 mg/droperidol 5 mg IV was superior to droperidol 10mg IV or olanzapine 10 mg IV for agitated patients.  The 2-drug combo worked in 75% of patients at ten minutes vs ~50% in the other two groups.  Also, fewer repeat sedative doses were needed when the drugs were combined.  Median time to sedation was only 5 minutes for the combo vs. 11 minutes for the other two individual drugs.  Adverse events were statistically similar in all groups, but the midazolam/droperidol group had a higher percentage temporarily needing jaw thrust or supplemental oxygen.

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For agitation, the combination of midazolam 5 mg/droperidol 5 mg IV was better and faster onset than droperidol 10 mg IV or olanzapine 10 mg IV.


Ann Emerg Med. 2016 Oct 10. pii: S0196-0644(16)30456-5. doi: 10.1016/j.annemergmed.2016.07.033. [Epub ahead of print]

Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial.

Taylor DM1, Yap CY2, Knott JC3, Taylor SE4, Phillips GA5, Karro J5, Chan EW6, Kong DC2, Castle DJ7.

Author information:

1Emergency Department, Austin Health, Heidelberg, Victoria, Australia. Electronic address: david.taylor@austin.org.au.

2Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia.

3Emergency Department, Royal Melbourne Hospital, Parkville, Victoria, Australia.

4Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia.

5Emergency Department, St Vincent’s Hospital, Victoria Parade, Victoria, Australia.

6Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.

7St Vincent’s Hospital and the University of Melbourne, Fitzroy, Victoria, Australia.



We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients.


We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes.


Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups’ adverse event rates and lengths of stay did not differ.


Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient.

Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

PMID: 27745766 [PubMed – as supplied by publisher]

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