Sedating Agitated Patients: A Comparison of Five Regimens

Sumit Patel, MD


January 28, 2019

Physicians treat agitated patients on a daily basis in the emergency department (ED). In many cases, it is challenging to distinguish the cause of the agitation, and these patients require thorough workups. A recent study, published in Annals of Emergency Medicine, provides us with better quality data to help guide our utilization of particular intramuscular medications used to treat acute agitation.[1]

In this prospective observational study, researchers compared the efficacy of four agents that can be utilized for undifferentiated agitation in the ED. The study was conducted at an inner city level 1 trauma center with an annual census of more than 100,000 visits between June 2017 and October 2017. In total, 737 patients were enrolled. Medications were dispensed according to a protocol that involved using one specific study agent during 3-week blocks. The intramuscular medications and doses tested included haloperidol 5 mg, midazolam 5 mg, olanzapine 10 mg, haloperidol 10 mg, and ziprasidone 20 mg.

The primary outcome was the proportion of patients adequately sedated at 15 minutes, using the Altered Mental Status Scale to quantify level of sedation. The only inclusion criterion was a patient requiring medication for acute agitation. Exclusion criteria were age younger than 18 years and being a prisoner or under arrest. The median age for enrolled patients was 40 years, with a range of 18-77 years. Researchers requested the treating medical professionals to categorize their suspected cause of the patient's agitation into one of the following: alcohol intoxication, drug intoxication, psychiatric, medical, or a combination of causes.

Data revealed that midazolam 5 mg had the highest proportion of patients adequately sedated at 15 minutes compared with the other medications. Olanzapine had a higher proportion of patients adequately sedated at the 15-minute mark than did haloperidol 5 mg, haloperidol 10 mg, and ziprasidone. Complication rates were low overall and similar across the various medications.

What Medications Do You Commonly Use to Sedate Patients?

This study was helpful, as it directly compared several medications used to treat undifferentiated agitation in the ED setting specifically in a prospective design. While a randomized controlled trial would have been ideal, researches explained at length that they had intended to conduct this type of study initially but ran into approval issues with the US Food and Drug Administration. The study certainly has important limitations, as it was conducted in a large urban academic ED. However, researchers did enroll a sufficient number of patients to power their study based on their calculations.

In my own practice, I have utilized intramuscular haloperidol with or without intramuscular lorazepam and diphenhydramine the most. I have also utilized ziprasidone, ketamine, and midazolam. My preferred option was midazolam, as I anecdotally had good results with this drug. However, midazolam has been on shortage in many of the departments in which I currently work, thus requiring the use of alternative options.

While this trial's results do not suddenly mean that we should all use intramuscular midazolam for the acutely agitated patient, it does provide some evidence to suggest it may be the right way to go in most cases. Ultimately, all medical professionals working in the ED will need to carefully determine which medication to use, and it can vary significantly case by case owing to the patient's age, prior medical history, allergies, and the suspected cause of the agitation. It is without a doubt that future studies will likely build on this trial and, hopefully, provide stronger evidence to help our decision-making for patient care.

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