Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study

Am J Emerg Med. 2021 Jun;44:306-311. doi: 10.1016/j.ajem.2020.04.013. Epub 2020 Apr 11.


Background: Clinicians often encounter agitated patients, and current treatment options include benzodiazepines and antipsychotics. Ketamine rapidly induces dissociation, maintains cardiovascular stability, spontaneous respirations, and airway reflexes. There are no prospective, randomized studies comparing ketamine to other agents in the initial management of acute agitation in the Emergency Department (ED).

Objective: Determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation.

Methods: This study was a prospective, single-institution, randomized, open-label, real world, standard of care pilot study. Adult patients with combative agitation were randomized to ketamine (4 mg/kg IM or 1 mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10 mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was sedation within 5 min, and secondary outcomes included sedation within 15 min, time to sedation, and safety.

Results: Ninety three patients were enrolled from January 15, 2018 to October 10, 2018. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p < 0.001). Patients who received ketamine experienced a significant, but transient tachycardia (p = 0.01) and hypertension (p = 0.01).

Conclusion: In patients with combative agitation, ketamine was significantly more effective than haloperidol/lorazepam for initial control of acute agitation, and was not associated with any significant adverse effects.

Keywords: Agitation; Haloperidol; Ketamine; Lorazepam; Sedation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anesthetics, Dissociative / administration & dosage
  • Anesthetics, Dissociative / therapeutic use*
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / therapeutic use
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use
  • Emergency Service, Hospital*
  • Female
  • Haloperidol / administration & dosage
  • Haloperidol / therapeutic use
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / therapeutic use*
  • Lorazepam / administration & dosage
  • Lorazepam / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Psychomotor Agitation / drug therapy*
  • United States


  • Anesthetics, Dissociative
  • Anti-Anxiety Agents
  • Antipsychotic Agents
  • Ketamine
  • Haloperidol
  • Lorazepam