Date: April 19th, 2021

Guest Skeptic: Dr. Kirsty Challen (@KirstyChallen) is a Consultant in Emergency Medicine and Emergency Medicine Research Lead at Lancashire Teaching Hospitals Trust (North West England). She is Chair of the Royal College of Emergency Medicine Women in Emergency Medicine group and involved with the RCEM Public Health and Informatics groups. Kirsty is also the creator of the wonderful infographics called #PaperinaPic.

Reference: Martel et al. Randomized Double-blind Trial Intramuscular Droperidol, Ziprasidone and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. AEM April 2021

Case: You are sitting minding your own business charting on shift when you become aware of shouting and banging from your ambulance bay.  On investigating you find a collection of nursing, EMS and hospital security personnel surrounding an obviously agitated patient with blood on his head who is attempting to punch them. The nurse wants to know what medications he can get to chemically restrain the patient.

Background: We have covered the issue of excited delirium back in SGEM#218 with a systematic review which found that the evidence base for most pharmacological treatments at that point was poor. Way back in 2013 we looked at haloperidol for agitation due to psychosis (SGEM#45) and concluded that it was an effective treatment but had common side effects.

Droperidol has been used widely, particularly in Australasia, for acute severe agitation. Unfortunately, an FDA Black Box warning and supply issues meant that droperidol effectively vanished from the US armamentarium from 2013-2019 and other agents were used and investigated.

Clinical Question: In patients needing parenteral sedation for acute agitation, is droperidol, ziprasidone or lorazepam intramuscularly  most effective and safe?

Reference: Martel et al. Randomized Double-blind Trial Intramuscular Droperidol, Ziprasidone and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. AEM April 2021

  • Population: Emergency department (ED) patients 18 years or old where the treating physician determined the need for parenteral sedation for acute agitation (it needed a patient or staff safety concern, not purely a high agitation score).
    • Exclusions: Prisoners or those in police custody, pregnant or breast-feeding, or with documented allergy to any study medications.
  • Intervention: Droperidol 5mg IM, Ziprasidone 10mg IM or Ziprasidone 20mg IM
  • Comparison: Lorazepam 2mg IM
  • Outcome:
    • Primary Outcome: Adequate sedation at 15 minutes was defined as an Altered Mental Status Scale (AMSS) of zero
    • Secondary Outcomes: Need for additional sedation, ED length of stay, respiratory depression (SpO2<90% requiring supplemental O2, EtCO2 falling by 10mmHg or rising by 15mmHg).

Dr. Marc Martel

This is an SGEMHOP episode, which means we have the lead author on the show. Dr. Martel is a practicing emergency physician at Hennepin County medical center in Minneapolis, Minnesota since 2000.  He has been a nocturnist for essentially his entire career.  Dr. Martel’s research focuses on finding the safest way to care for patients with acute agitation while respecting patient’s dignity, limiting restraint use, and efficiently getting them care they need.

Authors’ Conclusions: “Droperidol was more effective for sedation and was associated with fewer episodes of respiratory depression than lorazepam or either dose of ziprasidone.” 

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Unsure
  5. The study patients were recruited consecutively (i.e. no selection bias). No
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
  8. All groups were treated equally except for the intervention. Unsure
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. No
  11. The treatment effect was large enough and precise enough to be clinically significant. Yes

Results: They recruited 115 participants into the trial, 87 of whom were men. The mean age was around 40 years, and the underlying diagnosis was primarily alcohol intoxication, with other diagnoses being drug intoxication, head injury, and psychiatric conditions.

Key Result: Droperidol was more effective than ziprasidone or lorazepam in treating E.D. patients with acute agitation.

  • Primary Outcome: Adequate sedation at 15 minutes
    • 64% of the droperidol group vs 35% and 25% of the ziprasidone groups and 29% of the lorazepam group.
      • Droperidol: 16/25: 64% (95% CI; 45%-80%)
      • Ziprasidone 10mg: 7/28: 25% (95% CI; 13%-43%)
      • Ziprasidone 20mg: 11/31: 35%  (95% CI; 21%-53%)
      • Lorazepam 9/31: 29% (95% CI; 16%-47%)
  • Secondary Outcomes: 
    • More patients in the lorazepam group received additional sedative medication and were reported to have respiratory depression.

We have five nerdy questions for Marc to help us better understand his study better. Listen to the podcast to hear his responses to each of our questions.

1. Old Data: As you say in the discussion this data is from 2004-05 and explain the delay?   How do you think it will apply in the landscape of bath salts, crystal meth and spice?

2. Convenience Sample: You recruited when the research team was available (limitation of EM research). This could have introduced some selection bias because patients presenting on nights/holidays/weekends may be different than those who present at other times. Did you manage to cover the whole working week adequately (24/7/365)?

3. Subjectivity: Both your inclusion criteria and your primary outcome were subjective (whether a patient needed parenteral sedation and whether sedation was adequate). Do you think your team was consistent or have data on inter-rater reliability (IRR) and did you have training to improve this aspect of the study?

4. Altered Mental Status Scale (AMSS): You used the AMSS for the assessment of agitation and stated in the manuscript that it was a “validated” ordinal agitation scale. Three references were provided to support the statement. I was not familiar with AMSS and pulled the references. Two were not validation studies of the AMSS [ref 14 & 28]. The third reference said “the AMSS has not been formally evaluated except as a tool in assessing alcohol intoxication in which Miner et al. only used the responsiveness descriptor” Calver et al 2011 [ref 27]. Is there a formal validation of the AMSS in this patient population and, like Nerdy point #3, is there data on IRR?

5. Comparison Group: Did you consider comparing droperidol to ketamine which has been very popular these days or to a combination of drugs like the B52?

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions.

SGEM Bottom Line: Consider droperidol as a therapeutic option for agitated patients requiring parenteral sedation.

Case Resolution: You ask the nurse to prepare for parenteral sedation with droperidol while you initially apply your techniques of verbal de-escalation.

Dr. Kirsty Challen

Clinical Application: In my UK practice droperidol still isn’t widely available, so I will reach for haloperidol, but if droperidol becomes available I am likely to use it.

What Do I Tell My Patient?  When you were first brought in, you were very distressed and a threat to yourself and others. We gave you an injection of sedative so we could treat you safely with a low risk of causing side-effects.

Keener Kontest: Last weeks’ winner was Dr. Dennis Ren a PEM fellow in Washington DC. He knew the “P” in PRAM initially was for “preschool”.

Listen to the podcast this week to hear the trivia question. Email your answer to with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

SGEMHOP: Now it is your turn SGEMers. What do you think of this episode on droperidol for acute agitation? Tweet your comments using #SGEMHOP.  What questions do you have for Marc and his team? Ask them on the SGEM blog. The best social media feedback will be published in AEM.

Also, don’t forget those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article. We will put the process on the SGEM blog:

  • Go to the Wiley Health Learning website
  • Register and create a log in
  • Search for Academic Emergency Medicine – “April”
  • Complete the five questions and submit your answers

Those who are not AEM members can also claim CME credits for this SGEM episode. The content is always free but there is a small fee for the CME. This will help support this Free Open Access Project and your support is greatly appreciated.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.