Safety and efficacy of pharmacologic agents used for rapid tranquilization of emergency department patients with acute agitation or excited delirium

ABSTRACT

Introduction: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments.

Areas covered: This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization.

Expert opinion: Using antipsychotics and benzodiazepines – whether a single agent or combined – will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5–10 mg IM) and midazolam (5–10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.

KEYWORDS:

• Acute agitation
• rapid tranquilization
• excited delirium
• excited delirium syndrome
• emergency department
• safety

Article highlights

• Patients with acute agitation/excited delirium syndrome pose a significant risk to the safety of patients and health-care workers, and can delay patients’ medical evaluation.

• Several antipsychotics and benzodiazepines, and ketamine are available for rapid tranquilization with different pharmacologic properties and safety profiles.

• Droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either agent is used as a single agent.

• When combination therapy is use, midazolam, instead of lorazepam, with an antipsychotic agent (e.g. haloperidol or droperidol) may provide faster onset of sedation.

• Ketamine (2-5 mg/kg IM) is frequently used as a second-line agent for rapid tranquilization; but studies report higher rates of endotracheal intubation from airway compromise (e.g. hypoxia & apnea) compared to other agents.

• Use of low-dose ketamine (2 mg/kg IM) may be a prudent approach to minimize the risk of airway compromise while achieving adequate sedation.

This box summarizes the key points contained in the article.

Acknowledgments

Deborah M. Stein, ELS, provided language and technical editing of the manuscript.

Declaration of interest

NJ Connors: This research was supported in part by HCA Healthcare and/or an HCA Healthcare–affiliated entity. The views expressed in this presentation represent those of the author and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.