(Updated January 2023)

Executive Summary

Droperidol is a first generation antipsychotic (so-called typical antipsychotics, same class as haloperidol) that acts as a D2 dopamine receptor antagonist. Droperidol also has some histamine and serotonin antagonist properties (3). 

• It has a significant potential role in the ED because of its efficacy to treat a variety of clinical conditions, including undifferentiated agitation, migraine, vertigo, nausea, vomiting, cannabinoid hyperemesis, and pain (3, 4, 5, 6, 7, 10,  12). 

  • Droperidol or olanzapine are considered first-line medications to treat acute severe agitation in psychiatric patients, and both can be used in combination with benzodiazepines (7, 12).

• Its use differs amongst geographical locations, clinicians and ED protocols. Some EDs do indicate it on a daily basis, others don't; this phenomena is explained to a great degree because of the US-FDA Black Box Warning issued in 2001 (2). This warning has been deeply questioned (1, 3, 6, 11, 13), this is why droperidol has been regaining popularity and its use has been increasing over the last decade (11). Nonetheless it should not be used on patients with long QT syndrome or at an increased risk of QT prolongation. 

Adult dose for undifferentiated agitation in the ED (6, 12)

5-10mg IM

• Time to adequate sedation is usually 10 to 20 min with a time to peak effect of 30 min

Adult dose for migraine, acute vertigo, nausea or vomiting and cannabinoid hyperemesis (2, 4, 5, 10)

1.25-2.5mg IV or IM

Adult dose for undifferentiated agitation in the ED (6, 12)

5-10mg IM

• Time to adequate sedation is usually 10 to 20 min with a time to peak effect of 30 min.

• If used IM, may repeat dose in 30 min (max 20 mg in 24 hours).

• If used IV, may repeat dose in 5 min (max 20 mg in 24 hours)

• May be administered as monotherapy or in combination with a benzodiazepine.
  
  

Adult dose for migraine, acute vertigo, nausea or vomiting and cannabinoid hyperemesis (2, 4, 5, 10)

1.25-2.5mg IV or IM

• For nausea and vomiting an initial dose of 0.625mg may be sufficient

• Additional dose of 1.25mg may be necessary

Indications

• US FDA-labeled (2): 

  • Nausea and vomiting treatment and prevention (post-operative, post-procedural)

• Off-label: 

  • Agitation

  • Acute vertigo

  • Cannabinoid hyperemesis syndrome

  • Headache (migraine)

  • Chronic and neuropathic pain

US-FDA Black Box Warning issued in 2001, label citation (2)

• “Cases of QT prolongation and/or torsade de pointes have been reported in patients receiving droperidol at doses at or below recommended doses.  Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Due to its potential for serious proarrhythmic effects and death, droperidol should be reserved for use in the treatment of patients who fail to show an acceptable response to other adequate treatments, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS).

• Cases of QT prolongation and serious arrhythmias (e.g., torsade de pointes) have been reported in patients treated with droperidol. Based on these reports, all patients should undergo a 12-lead ECG prior to administration of droperidol to determine if a prolonged QT interval (i.e., QTc greater than 440 msec for males or 450 msec for females) is present. If there is a prolonged QT interval, droperidol should NOT be administered. For patients in whom the potential benefit of droperidol treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2-3 hours after completing treatment to monitor for arrhythmias.

• Droperidol is contraindicated in patients with known or suspected QT prolongation, including patients with congenital long QT syndrome.

• Droperidol should be administered with extreme caution to patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). 

• Other risk factors may include age over 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anesthetics, and IV opiates. Droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect.”

A copious amount of clinical data, review articles and society statements have emerged over the last decade defending droperidol safety when used properly and in the doses that usually are sufficiently needed in the ED (1, 3). 

Society positions, review articles, expert opinion:

1. 2021 ACEP - American College of Emergency Physicians

   • 2021 Severe Agitation in the ED Task Force Report
     ACEP Task Force Report on Hyperactive Delirium with Severe Agitation in Emergency Settings, 2021

   • 2021 Policy Statement
     ACEP - Use of Droperidol in the Emergency Department 2021

2. 2020 EM-RAP - Emergency Medicine Reviews and Perspectives

Droperidol is Back by Reuben Strayer

3. 2019 FOAMcast - An Emergency Medicine Podcast

   • FOAMCAST 2019 Droperidol (and Haloperidol) Review by emergency physicians Jeremy Faust and Lauren Westafer

   • Droperidol and Butyrophenones on Spotify

4. 2015 American Academy of Emergency Medicine (AAEM)

   • 2015 Safety of Droperidol Use in the ED Position Statement

Pregnancy

• AU-TGA pregnancy category: C

• US-FDA pregnancy category: C
  
  

Lactation

• There are no published data about droperidol on its excretion on breast milk, but available molecular data on its pharmacokinetic characteristics (high plasma protein binding, large volume of distribution and short half-life), make it very unlikely its excretion into breast milk in significant amounts (14).

• Therefore it should be considered safe during breastfeeding  at least in small and short term doses usually given in the ED.  

Overview, label and safety

1. Perkins J, Ho JD, Vilke GM, DeMers G. American Academy of Emergency Medicine Position Statement: Safety of Droperidol Use in the Emergency Department. J Emerg Med. 2015;49(1):91-97. doi:10.1016/j.jemermed.2014.12.024
   Pubmed

2. NIH-NLM (National Institutes of Health - National Library of Medicine). DailyMed. Label: DROPERIDOL injection, solution. Updated in October 2019.
   DailyMed

3. Gaw CM, Cabrera D, Bellolio F, Mattson AE, Lohse CM, Jeffery MM. Effectiveness and safety of droperidol in a United States emergency department. Am J Emerg Med. 2020;38(7):1310-1314. doi:10.1016/j.ajem.2019.09.007
   Science Direct (Open Access)

Specific indications

4. Irving C, Richman PB, Kaiafas C, Eskin B, Ritter A, Allegra J. Droperidol for the treatment of acute peripheral vertigo. Am J Emerg Med. 1999;17(1):109-110. doi:10.1016/s0735-6757(99)90037-2
   Pubmed

5. Miner JR, Fish SJ, Smith SW, Biros MH. Droperidol vs. prochlorperazine for benign headaches in the emergency department. Acad Emerg Med. 2001;8(9):873-879. doi:10.1111/j.1553-2712.2001.tb01147.x
   Pubmed

6. DORM Study - Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010;56(4):392-401.e1. doi:10.1016/j.annemergmed.2010.05.037
   Pubmed

7. Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013;61(1):72-81. doi:10.1016/j.annemergmed.2012.07.118
   Pubmed

8. DORM II Study - Calver L, Page CB, Downes MA, et al. The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015;66(3):230-238.e1. doi:10.1016/j.annemergmed.2015.03.016
   Pubmed

9. Furyk JS, Meek RA, Egerton-Warburton D. Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. Cochrane Database Syst Rev. 2015;2015(9):CD010106. Published 2015 Sep 28. doi:10.1002/14651858.CD010106.pub2
   Pubmed Central (Open Access)

10. Lee C, Greene SL, Wong A. The utility of droperidol in the treatment of cannabinoid hyperemesis syndrome. Clin Toxicol (Phila). 2019;57(9):773-777. doi:10.1080/15563650.2018.1564324
    Pubmed

11. Kramer KJ. The Surprising Re-emergence of Droperidol. Anesth Prog. 2020;67(3):125-126. doi:10.2344/anpr-67-03-14
    Pubmed Central (Open Access)

12. ACEP Task Force Report on Hyperactive Delirium with Severe Agitation in Emergency Settings. Approved by the ACEP Board of Directors, June 23, 2021.
    ACEP

13. ACEP Policy Statement. Use of Droperidol in the Emergency Department, 2021.
    ACEP (Open Access)

14. APILAM (Association for promotion of and cultural and scientific research into breastfeeding). e-lactancia. Droperidol. Updated June 2022. Accessed February 12, 2023.
    E-lactancia