Introduction

  • While verbal de-escalation should always be attempted first, chemical sedation of acutely agitated patients may be required if the patient becomes a danger to themselves or to ED staff.
  • In 2001, the U.S. FDA issued a black-box warning for droperidol and QTc prolongation based on observational after-market data
  • The majority of these cases were reported at higher doses than those used in the ED (65-300 mg)
  • Multiple prospective studies have demonstrated safe and effective use of droperidol in the ED for acute agitation.

Clinical Detail

Pharmacology1,2
MOAButyrophenone D2 receptor antagonist
Dose5-10 mg alone
2.5-5 mg coadministered with midazolam
AdministrationRoutes: IM or IV
PK/PDOnset: 3-10 min
Peak: ~ 30 min
Duration: 2-4 hours
Adverse EffectsMild to moderate hypotension
Bradycardia
QTc prolongation (dose dependent)
Extrapyramidal symptoms (dystonia, akathisia)
Drug Interactions and warningsPheochromocytoma: may cause severe hypertension or tachycardia
Other CNS depressants- potentiating effect
CompatibilityCompatible with NS, D5W, or LR
CommentsNo renal dose adjustments required

Evidence

Author, yearDesign/ sample sizeIntervention & ComparisonOutcome
Martel, 20203DB, RCT (n=115)• IM Droperidol 5 mg
• IM Ziprasidone 10 mg
• IM Ziprasidone 20 mg
• IM Lorazepam 2 mg		Droperidol was more effective than ziprasidone 10mg or 20 mg, and lorazepam at 15 minutes
o 64% compared to 25%, 35%, 29%
Cole, 20204Observational (n= 16,546)• IV/IM DroperidolThe mean QTc difference was +3.3 milliseconds (ms) after droperidol
The incidence of torsades des pointes (TdP) was 1/16,546 or 0.006%
Yap et al, 20175Subgroup analysis of RCT (n=92)• IV Midazolam 5 mg + IV Droperidol 5 mg
• IV Droperidol 10 mg
• IV Olanzapine 10 mg		At 10 minutes, significantly more patients in the midazolam-droperidol group
o Midazolam-droperidol 85.3% compared to 46.7% droperidol monotherapy, and 50% olanzapine monotherapy
Taylor et al. 20176RCT (n= 345)• IV midazolam 5 mg + IV droperidol 5 mg
• IV Droperidol 10 mg
• IV Olanzapine 10 mg		Midazolam + droperidol was faster than either droperidol or olanzapine alone, and required less rescue doses
o 76.6% compared to 49.6% and 49.2% respectively
Calver 20207Observational (n= 1,009)• IM/IV Droperidol 10 mgThirteen of 1,009 or 1.3% patients had an abnormal QT
Median time to sedation was 20 minutes (IQR 10 to 30 minutes)
No cases of torsades de pointes
Chan et al. 20138DB, RCT (n=336)• IV Droperidol 5 mg + midazolam
• IV Olanzapine 5 mg + midazolam
• IV Placebo + midazolam		Combination of droperidol or olanzapine + IV midazolam resulted in faster median time to sedation ( 6, 5 min vs. 10 min) than midazolam monotherapy
The 3 groups' adverse event profiles and lengths of stay did not differ.
Isbister et al. 20109DB, RCT (n = 91)• IM Midazolam 10 mg
• IM Droperidol 10 mg
• IM Droperidol 5 mg + IM midazolam 5 mg		IM droperidol resulted in similar security duration as midazolam or midazolam/droperidol combination,
Droperidol required less additional sedation, had a lower rate of adverse effects
Droperidol had no cases of arrhythmias or QT prolongation
Knott et al. 200610DB, RCT (n=74)• IV Midazolam 5 mg
• IV Droperidol 5 mg		28.1% more patients were sedated at 5 min with IV midazolam vs. droperidol
o At 10 min ~ 50% of patients were adequately sedated in both the midazolam and droperidol groups.
Less patients in the droperidol group required additional sedation within 60 min vs. midazolam group

Conclusions

  • Droperidol appears safe and effective at the low doses required for acute agitation in the ED and results in less respiratory depression than midazolam monotherapy.
  • Droperidol does not have to be administered with a benzodiazepine to achieve rapid and adequate sedation
  • There is a low rate of akathisia with droperidol that can be managed with IV diphenhydramine

References

  • American Regent. Droperidol Package Insert. Shirley, NY; 2009.
  • 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
  • Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg
  • Med. 2020;00:1-14. doi:10.1111/acem.14124
  • Cole JB, Lee SC, Martel ML, Smith SW, Biros MH, Miner JR. The Incidence of QT Prolongation and Torsades des
  • Pointes in Patients Receiving Droperidol in an Urban Emergency Department. West J Emerg Med. 2020 Jul
  • 2;21(4):728-736. doi: 10.5811/westjem.2020.4.47036. PMID: 32726229; PMCID: PMC7390553.
  • Yap CYL, Mcd Taylor D, Knott JC, et al. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized
  • controlled trial. Addiction. 2017;112:1262-1269. doi:10.1111/add.13780
  • Taylor DMD, Yap CYL, Knott JC, et al. Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A
  • Randomized Clinical Trial. In: Annals of Emergency Medicine. Vol 69. Mosby Inc.; 2017:318-326.e1.
  • doi:10.1016/j.annemergmed.2016.07.033
  • Calver L, Page CB, Downes MA, Chan B, Kinnear F, Wheatley L, Spain D, Isbister GK. The Safety and Effectiveness of
  • Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015
  • Sep;66(3):230-238.e1. doi: 10.1016/j.annemergmed.2015.03.016. Epub 2015 Apr 15. PMID: 25890395.
  • Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DCM. 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
  • 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
  • Knott JC, Taylor DM, Castle DJ. Randomized Clinical Trial Comparing Intravenous Midazolam and Droperidol
  • for Sedation of the Acutely Agitated Patient in the Emergency Department. Ann Emerg Med. 2006;47:61-67.
  • doi:10.1016/j.annemergmed.2005.07.003
Tags:droperidol acute agitation QT sedation