Original ResearchRandomized Clinical Trial Comparing Intravenous Midazolam and Droperidol for Sedation of the Acutely Agitated Patient in the Emergency Department
Introduction
The management of acutely agitated patients, whether because of psychiatric illness or drug or alcohol intoxication, results in a disproportionate use of emergency department (ED) resources. A number of techniques are used to placate such patients, including setting limits, clear explanations of procedures, and chemical and physical restraint. Restraints are used only when individuals are at risk of harming themselves or those around them, including staff and other patients, and is required in 0.3% to 2% of all ED presentations.1, 2
Reviews of Australasian, United Kingdom, and US restraint practices indicate that the drugs used for restraint in the ED are neuroleptics and short-acting benzodiazepines.1, 3, 4 The majority of acute sedation studies has examined the management of acute agitation in psychiatric wards or ICUs. These settings often require long sedation times, often measured in hours, and either lack applicability to the general ED population or lack the power to exclude differences between agents.5, 6, 7, 8
Benzodiazepines are effective sedatives, with midazolam and diazepam (but not lorazepam) available parenterally in Australasia, and are used frequently as first-line agents.1 Alternatives include the neuroleptics; droperidol has been shown to be more effective as a sedative compared with haloperidol.7, 9 For rapid tranquillization requiring intravenous administration, midazolam and droperidol have gained ascendancy in Australasian EDs.1, 2
The decision to sedate an acutely agitated patient requires a rapid response to prevent harm. Because of the complex issues surrounding the treatment of these individuals, the best available evidence-based therapy should be used in their treatment.
Midazolam and droperidol have not been compared for treatment of acutely agitated patients. The aim of this study is to compare these agents with respect to time to adequate sedation, the need for subsequent sedation within 60 minutes, and adverse event rates. We hypothesized that there would be no difference between the drugs with respect to these outcomes.
Section snippets
Study Design and Setting
The study was a double-blind, randomized, clinical trial of intravenous midazolam versus droperidol conducted in the ED of a large Australian metropolitan university hospital with approximately 50,000 attendances annually.
Selection of Participants
Patients were eligible for enrollment if they were aged 18 to 65 years (inclusive) and exhibited marked agitation that required chemical restraint as deemed by a consultant (attending) emergency physician or a senior accredited resident of the Australasian College for
Characteristics of Study Subjects
One hundred seventy patients were enrolled by study-pack allocation. Of these, 17 packs were lost so that data on 153 patients were available for analysis (Figure 1). Table 1 shows patient characteristics; there were no significant differences between the patients in each arm of the trial. A number of patients sedated before their full details became available were subsequently found to be outside the age inclusion criteria (18 to 65 years). Six patients in the midazolam arm were aged 15, 17,
Limitations
A number of limitations in this study have been identified.
Selection bias may have occurred if physicians failed to enroll patients for whom they had a particular preference in terms of pharmacologic management. It was difficult to determine the number of eligible patients not enrolled. In our department, it is likely to be low because midazolam and droperidol are the preferred sedation agents and used interchangeably on an ad hoc basis; it is uncommon for a particular preference for either
Discussion
We believe this to be the first blinded, randomized, clinical study comparing midazolam and droperidol for rapid sedation of agitated patients in a general ED. There was no difference in the time to sedation; however, more patients were sedated in the first 5 minutes when midazolam was used.
The TREC collaborative group14 (Rio) and Nobay et al15 found midazolam results in a shorter time to sedation than a neuroleptic. However, those studies used intramuscular haloperidol, and haloperidol has
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Supervising editor: Steven M. Green, MD
Author contributions: JK was principal investigator. JK, DT, and DC were responsible for initial study design. JK conducted the study and collected the data. JK, DT, and DC conducted data analysis and manuscript preparation. JK was principally responsible for the statistical analysis of the data. JK takes responsibility for the paper as a whole.
Funding and support: This study was supported by a postgraduate scholarship from the National Health and Medicine Research Council and a research grant from the Australasian College for Emergency Medicine (Morson Taylor Award).
Presented at the 8th International Conference for Emergency Medicine, June 2004, Cairns, Queensland, Australia.
Reprints not available from the authors.