Toxicology/original researchRandomized Controlled Trial of Intramuscular Droperidol Versus Midazolam for Violence and Acute Behavioral Disturbance: The DORM Study
Introduction
Violence and aggression in the emergency department (ED) is a difficult and dangerous problem that can result in harm to the patient or staff. The majority of cases are due to acute delirium from alcohol intoxication, are due to psychostimulant toxicity, or are associated with deliberate self-harm and drug overdose.1, 2 Many of these patients will not respond to verbal de-escalation or accept oral medications, and some arrive in police custody already restrained. To allow the safe assessment, diagnosis, and treatment of these patients, parenteral sedation and physical restraint are usually required.
There is ongoing controversy about the safest and most effective medications for sedation of violence and acute behavioral disturbance in the ED.3 There is no type of medication that provides sedation in all patients with no adverse effects. Currently, the 2 major groups of medications used are benzodiazepines (midazolam, diazepam, and lorazepam) and antipsychotics (haloperidol, droperidol, and olanzapine). There is increasing evidence that the benzodiazepines fail to sedate a proportion of these patients because of benzodiazepine tolerance, and when larger doses are used a proportion are oversedated.4 Antipsychotics have been associated with cardiac dysrhythmias and QT prolongation,5, 6 and some are only mildly sedating, such as haloperidol.
Droperidol is a highly sedative antipsychotic that was widely used until the Food and Drug Administration in the United States issued a black box warning in 2001 because of concerns about QT prolongation and torsades des pointes. This was based on little evidence7 and an unusual number of spontaneous reports on 1 day, mainly from outside the United States.8 A systematic review of droperidol use failed to support a strong association with QT prolongation and torsades des pointes,7 and droperidol was not found to be commonly associated with torsades des pointes in a systematic review of torsades des pointes cases.9 However, the use of droperidol has fallen out of favor since the black box warning despite decades of its effective use in EDs and psychiatric units around the world.10, 11 Few controlled trials have been reported assessing its effectiveness for sedation and safety compared with that of other agents in the ED.
There is limited information about the intramuscular route for sedative drugs in violent and acute behavioral disturbance,2 which is often the only possible route of administration for these patients. Intravenous sedation requires increased staffing; otherwise, it is effectively impossible and potentially dangerous to attempt to gain intravenous access. There is a real risk of needlestick injuries or other physical injuries to the staff, and most guidelines suggest intramuscular sedation in this setting. Antipsychotic medications such as droperidol are an option to benzodiazepines for intramuscular sedation, but there are few studies comparing intramuscular benzodiazepines with antipsychotics. To our knowledge, there is only 1 trial of intramuscular droperidol that compared it with midazolam and ziprasidone.2 This showed that droperidol was at least as effective as midazolam, whereas midazolam required more rescue sedation. Studies of intravenous droperidol suggest it has a longer duration of action compared with that of benzodiazepines2, 12 but potentially a slower onset of action.13 All of these previous trials have used low doses, with many patients requiring further sedation. No previous trial has investigated the combination of intramuscular benzodiazepines and droperidol.
This study aimed to determine whether intramuscular droperidol, midazolam, or the combination results in a shorter duration of the violent and acute behavioral disturbance episode defined by the time security staff are required. In addition, the study aimed to determine for each drug treatment the requirement for additional sedation, staff and patient injuries, further episodes of violent and acute behavioral disturbance, and drug-related adverse effects, including the occurrence of QT prolongation with droperidol.
Section snippets
Study Design and Setting
We undertook a blinded randomized controlled trial of intramuscular droperidol versus midazolam versus a combination of both for the sedation of violent and acute behavioral disturbance in the ED. The patients, the health care providers, and the investigators were blinded to the treatment arms. The primary outcome was the duration of the violent and acute behavioral disturbance.
The study was undertaken from August 2008 to July 2009 in a hospital with a large number of patients who had violent
Results
There were 223 ED patient presentations with violence and acute behavioral disturbance during the 1-year study period. Of these, 121 were excluded and a further 11 were missed (Figure 1), resulting in 91 patient presentations being included. All 91 presentations received the trial medication and had data collected for at least 90 minutes, and 79 presentations remained in the ED until the completion of the trial at 6 hours. Of 79 patients involved, 69 presented on 1 occasion, 8 presented on 2
Limitations
A concern with any study of sedative medications in this patient population is the possibility of interaction between the drugs being administered in the trial and any drugs or alcohol that the patients have already ingested. For example, patients intoxicated with alcohol may be more likely to become oversedated with benzodiazepines. Figure 5 is an attempt to address this issue. It suggests that alcohol is associated with a larger number of adverse effects, and this appears to be mainly with
Discussion
This study shows that intramuscular droperidol is effective and safe for the sedation of violence and acute behavioral disturbance in the ED. In comparison with intramuscular midazolam, droperidol resulted in a similar security-duration requirement, required less additional sedation, and had a lower rate of adverse effects. Most revealing was the predictable response to droperidol according to the Altered Mental Status Scale, with rapid and then persistent sedation but not oversedation (Figure 4
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Please see page 393 for the Editor's Capsule Summary of this article.
Supervising editor: Debra E. Houry, MD, MPH
Author contributions: GKI and MAD designed the study. LAC coordinated recruitment. GKI, LAC, CBP, and JLB undertook data collection. GKI, LAC, and BS undertook the analysis. GKI wrote the article, and LAC, CBP, BS, JLB, and MAD and reviewed drafts. GKI takes responsibility for the paper as a whole.
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The study was funded by NSW Health Drug and Alcohol Research Grants Program 2007/08, Australia. Dr. Isbister is funded by an NHMRC Clinical Career Development Award ID300785.
Eam CME Credit: Continuing Medical Education is available for this article at http://www.ACED-EMedHome.com.
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