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Ketamine – Safe Takedown for Agitated Patients

June 1, 2020

Editor’s note: Improperly restraining a person may cause harm or death. It is urgent to learn the Art of the Chemical Takedown, as Rob Orman put it. This study offers one more tool to help you help patients with agitation. – Clay Smith

Written by Sam Parnell

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For patients with combative agitation, ketamine resulted in more rapid and efficacious sedation compared to a combination of haloperidol and lorazepam. In addition, ketamine was not associated with significantly increased risk of serious adverse events.

Why does this matter?
Acute agitation is frequently encountered in the Emergency Department. Patients do not always respond to verbal de-escalation, and chemical sedation is sometimes warranted. Many clinicians still go with the tried and true “B-52” combination (Benadryl 50mg, Haloperidol 5 mg, and Lorazepam 2 mg IM) as initial management for combative or agitated patients. However, these medications have inherent risks including respiratory depression, QTc prolongation, arrhythmia, drug-drug interactions, and polypharmacy. Furthermore, IM formulations of these medications can take up to 20-30 minutes to become maximally effective. So, are there better pharmacologic options for management of acute agitation?

Ketamine dart for the safe, effective takedown
This was a prospective, single-institution, randomized, open label pilot study of 93 adult patients with acute combative agitation comparing ketamine (4 mg/kg IM or 1 mg/kg IV, max dose 500 mg) to a combination of haloperidol and lorazepam (haloperidol 5–10 mg IM or IV + lorazepam 1–2 mg IM or IV). Most patients (93%) were given these medications intramuscularly. Patients who received ketamine were more likely to be sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001) with faster median time to sedation (15 vs 36 min, p < 0.001). Ketamine was associated with a significantly increased incidence of hypertension and tachycardia and a trend toward hypoxia that was not statistically significant (21% vs 10%, p = 0.238). There was no statistically significant difference in incidence of nausea/vomiting, intubation, QTc prolongation, arrhythmia, or cardiac arrest between the two groups.

This was a small, single-center study that had multiple limitations. However, the results strongly suggest that ketamine leads to more rapid and deeper sedation than haloperidol/lorazepam for patients with acute agitation. A larger study would be helpful for validation, but right now it looks like ketamine may be one of the best single agents for patients who are dangerously combative and need rapid intramuscular sedation. Just watch out for the hypoxia that may result from that deep sedation!

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Efficacy of Ketamine for Initial Control of Acute Agitation in the Emergency Department: A Randomized Study. Am J Emerg Med. 2020 Apr 11;S0735-6757(20)30241-2. doi: 10.1016/j.ajem.2020.04.013. Online ahead of print.

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