Episode 3- “Vitamin D”: Droperidol for agitation in the ER

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Episode Summary:

In this episode, we discuss the use of droperidol for the treatment of agitation in the ER setting. Please remember to subscribe to our podcast and leave us a comment!

Show Notes:

Key Points:

Droperidol for agitation in the ER:
– Droperidol has been used safely for the treatment of agitation in the ER setting for decades (although this is an off-label use)
– Droperidol has been shown to require less airway interventions, less repeated dosing, and has a more predictable effect when compared to benzodiazepine (BZD) agents when used for agitation
– Droperidol comes as a liquid that does not require reconstitution and can be given concomitantly with BZDs, unlike olanzapine
– A reasonable dose is 5-10 mg given intravenously or intramuscularly, with lower dosing for elderly, lower-weight patients and higher dosing for younger, larger patients
Er-Rx Episode 3


Knott JC, et al. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med. 2006; 47: 61-67

Isbister GK, et al. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010; 56: 392-401

Chan EW, et al. Intravenous droperidol or olanzapine as adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013; 61: 72-81

Taylor, DM, et al. Midazolam-droperidol, droperidol, or olanzapine for acute agitation: a randomized clinical trial. Ann Emerge Med. 2017; 69(3): 318-326

Olanzapine (Zyprexa) [prescribing information]. Princeton, NJ: Sandoz; 2019


Hello, everyone. Welcome back to ER-Rx. In today’s episode, we are going to discuss the use of droperidol in the ER for the treatment of agitation. Droperidol, all after being used in the ER for over 40 years, got hit with an FDA black box warning in 2001. The FDA cited significant concerns about the risk of cardiac arrhythmias. Specifically QTc prolongation. This caused hospitals to restrict the use of droperidol and other hospitals outright banned its use. However, since 2001 there have been a lot of studies that came out questioning the need for this black box warning against droperidol. And just as people were starting to use it again, in 2012 it went on shortage, and then it was gone. To be clear; droperidol is FDA approved for post-op nausea and vomiting only. However, it is used off-label for the treatment of headaches, migraines, as well as agitation. Recently, droperidol has become available again, and it has been a heavy favorite in my ER as well as many ERs across the country. So , what is so tantalizing about “vitamin D”?

Now, both the FDA black box morning in 2001 and the manufacturer shortage in 2012 predates my time working in the ER. So when this drug was available again, and all of my ER colleagues were very excited about this, I had no idea why. So, I had to do my own literature searches. Let’s discuss a couple studies that have compared droperidol to other agents for the treatment of acute agitation in the ER. In a study from 2006 Knott , et al. looked at 74 acutely agitated adults who got either five mg of midazolam, or five mg of droperidol IV every five minutes until they were adequately sedated. Time to sedation was equal between the groups at about 10 minutes each. However, the group that received midazolam required three airway management events, including one intubation. In the droperidol group, there were three dystonic reactions and there actually was one arrhythmia. However, this arrhythmia was actually bradycardia; the patient did find without any intervention, and there was no increase in QTc’s in either group.

In 2010 Isbister, et al. published the famous “DORM” study where they tested 10 mg of droperidol, 10 mg of midazolam, or five mg of each drug given together IM in 91 violent and agitated adults in the ER. There was no difference in median duration of the agitation event (at around 20 minutes). There was also no difference in patient or staff injuries and further episodes of violence and agitation between the groups. However, additional sedation was required in 62% of the midazolam-alone group versus only 33% in the droperidol group. The midazolam group also had much more adverse drug events, with up to 1/4 of their population experiencing some sort of adverse drug event. 6% of droperidol patients did have an abnormal QTc. However, this was the same between all groups. The authors concluded that droperidol produced a more consistent and moderate level of sedation compared with the very variable and unpredictable sedation that was seen in the midazolam group. This is actually something that I see firsthand with my experience in the ER as well.

Obviously both of studies that we reviewed today had compared droperidol to benzodiazepine agents. As far as the question of how does droperidol stack up to other IV or IM anti-psychotics, studies have shown that droperidol seems to be about equivalent to IV or IM olanzapine. And as a side note, both droperidol and olanzapine seem to work better than Haldol. In my ER, I feel like providers like to reach for droperidol before they reach for olanzapine, and this is due to a couple of reasons. The first reason is that in my ER, olanzapine comes as a powder which has to be reconstituted prior to use. This is very frustrating for both the pharmacists that mix up medications in my ER as well as for the nurses. And also, it’s frustrating to the providers because now there is a delay in administering this agent. The second reason is that per olanzapine’s package insert, we should avoid the concomitant administration of IV or IM olanzapine with IV or IM benzodiazepine agents due to the risk of severe cardiopulmonary depression. It is therefore the policy of my hospital to not give any IV or IM benzodiazepines within one hour of giving IV or IM olanzapine.

In conclusion, I can definitely understand now why ER providers were so excited when droperidol came back. I have to admit, after all of my literature searches, as well as my personal experience in the ER with this agent, I can safely say that I have drank the “Vitamin D” Kool Aid.

Thank you so much for your time. Please don’t forget to check out our website at errxpodcast.com. There you can see a list of all of our past episodes, check out our show notes, look at our references, as well as a read a full transcript of each episode.

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