Patients with severe agitation are frequently encountered in the emergency department (ED) setting. The first steps in the management of agitation are de-escalation and calming techniques, situational modifications, and, if needed, oral medications. Unfortunately, these techniques may be insufficient. Emergency departments can be crowded and chaotic, further exacerbating mental health issues. Intoxication with drugs and/or alcohol can inhibit comprehension. As a result, patients with severe agitation may require sedating medication for the safety of the patient and treating clinicians.

When this happens—what medication(s) do you reach for? Is it haloperidol and lorazepam (known as “5 and 2”)? A “B52” (the prior combination plus diphenhydramine)? Monotherapy with olanzapine, droperidol, haloperidol, ketamine, or midazolam? The ideal medications work very quickly, does not require additional dosing or rescue medications, and does not overly sedate a patient or cause respiratory depression.

Choices in the ED

The choice of sedating or calming medication is often an inherited or local practice, rather than rooted in evidence. We reach for what we are comfortable with, which is usually what we learned during training. Additionally, the evidence is complex—studies compare various combinations of medications, different doses, and different routes (intravenous [IV] versus intramuscular [IM]). A new clinical policy from the American College of Emergency Physicians (ACEP) seeks to distill the often indirect evidence and guide clinicians in choosing the best parenteral agents for patients with severe agitation.¹ The winners: droperidol/midazolam and ketamine.

The clinical policy gives a Level B recommendation, which carries a moderate level of scientific certainty, to the use of a combination of droperidol and midazolam (or another atypical antipsychotic plus midazolam) for “more rapid and efficacious treatment of severe agitation.” This is a critical point. Rapid and efficacious. Many agents can sedate patients sufficiently to proceed with medical evaluation and treatment safely. However, we should only use these medications when other options have failed and the need is critical. Under these circumstances, rapidity is critical for the safety of the patient, the treating team, and other nearby patients.

Speed Matters

The combination of droperidol and midazolam appears to result in rapid sedation, requires fewer additional medications, and has a favorable safety profile in agitated ED patients. Though once maligned due to a black box warning, droperidol has an extensive safety record.² A randomized study found that droperidol (5 mg IV) plus midazolam (5 mg IV) resulted in a higher proportion of patients adequately sedated at 10 minutes compared with droperidol (10 mg IV) or olanzapine (10 mg IV) alone.³ In a similar vein, another randomized study found that a combination of droperidol 5 mg IV with midazolam or olanzapine 5 mg IV and midazolam resulted in quicker time to adequate sedation than intravenous midazolam alone. Both droperidol and olanzapine probably work slightly more quickly than haloperidol.³