The latest trial by Taylor et al provides further support for the efficacy of droperidol and midazolam coadministration in sedating agitated emergency department (ED) patients. The authors’ detailed reporting of randomization and allocation concealment was exemplary, and we believe that many clinicians without access to droperidol will regard this study with envy. We also commend the authors for their broad inclusion criteria, which enrolled patients with drug-induced agitation and alcohol intoxication, and those who had received sedative medications in the previous 12 hours. Given that 88 of 349 study subjects (25%) were in the latter group, we are curious to know more about the type, dose, and timing of drugs administered during the earlier, unsuccessful attempts at sedation and specifically how they factored into the multivariate Cox analyses. Local sedation practice patterns may affect the generalizability of the authors’ results because of the delayed effects of previously administered drugs and their interactions with droperidol, olanzapine, and midazolam.

The choice of “adequate sedation at 10 minutes” as a primary outcome shows remarkable consideration for ED time and resource constraints. Unfortunately, we were surprised to find no mention of this measure when reviewing the study’s Australian New Zealand Clinical Trials Registry file (trial ID ACTRN12614000980639) at letter submission. Rather, the prespecified primary outcome “time to sedation” in the registry file was downgraded to a secondary outcome in this publication. Given the assiduous documentation of mental status at 5-minute intervals, there was a clear opportunity for exploratory analysis of sedation scores at different points. Thus, we ask Taylor et al to clarify whether the discrepancy in this report was due to clerical oversight or an undeclared change in the primary outcome after trial registration.

Last, we would like to highlight the 9% risk of airway obstruction in the midazolam-droperidol group, which was more than twice that of patients receiving droperidol or olanzapine alone. Although the risks of a threatened airway are statistically nonsignificant, readers are reminded to consider whether they outweigh the benefits of more rapid sedation in each agitated patient. Perhaps a clearer risk assessment of airway obstruction could be made if the authors reported on its observed associations with alcohol intoxication or other distinct diagnoses presenting with agitation.