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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

    MOA

    Butyrophenone D2 receptor antagonist

    Dose

    5-10 mg alone

  • 5-5 mg coadministered with midazolam

    • Administration

    Routes: IM or IV

    PK/PD

    Onset: 3-10 min

    Peak: ~ 30 min

    Duration: 2-4 hours

    Adverse

    Effects

    Mild to moderate hypotension

    Bradycardia

    QTc prolongation (dose dependent)

    Extrapyramidal symptoms (dystonia, akathisia)

    Drug

    Interactions

    and warnings

    Pheochromocytoma: may cause severe hypertension or tachycardia

    Other CNS depressants- potentiating effect

    Compatibility

    Compatible with NS, D5W, or LR

    Comments

    No renal dose adjustments required

    (Britany Byrkit & [email protected]

Evidence

    Author,

    year

    Design/ sample

    size

    Intervention & Comparison

    Outcome

    Martel,

    20203

    DB, 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,

    20204

    Observational

    (n= 16,546)

    • IV/IM Droperidol

    • The 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,

    20175

    Subgroup

    analysis of RCT

    (n=92)

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

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