IV droperidol or olanzapine as adjuncts to midazolam for the acutely agitated patient: a multi-centre, randomised, double-blind, placebo-controlled, clinical trial

Abstract

OBJECTIVES: To determine if IV droperidol or olanzapine, as adjuncts to midazolam administration, improve sedation quality for the acutely agitated ED patient METHODS: We undertook a randomised, double-blind, placebocontrolled, double-dummy, clinical trial in three EDs (August 2009 to March 2011). Adult patients requiring IV drug sedation for acute agitation were enrolled. Each was randomised to receive an IV bolus of either saline (control), droperidol (5 mg) or olanzapine (5 mg). This bolus was immediately followed by an IV midazolam bolus (2.5–5 mg) then additional boluses until sedation to a predetermined endpoint was achieved. The primary outcome was time to sedation. Secondary outcomes were the need for ‘rescue’ sedation and adverse events. RESULTS: 336 patients were enrolled. The baseline characteristics of the groups did not differ (p > 0.05). However, the median (IQR) times to sedation (min) differed signifi cantly (p < 0.001): control group 10 (4–25), droperidol 6 (3–10), olanzapine 5 (3–10). At any time point, patients in the droperidol and olanzapine groups were ∼1.6 times more likely to be sedated compared to controls: droperidol and olanzapine group hazard ratios (95%CI) were 1.58 (1.21–2.06) and 1.64 (1.25–2.15), respectively, (p = 0.001). The droperidol and olanzapine groups required less rescue sedation and alternative drug use at any time after initial sedation had been achieved (p < 0.05). The group adverse event profi les and lengths of stay did not differ (p = 0.21 and 0.32, respectively). CONCLUSION: Droperidol or olanzapine administration, as adjuncts to midazolam, is safe and signifi cantly improves sedation quality. These fi ndings will inform best-practice for sedation of the acutely agitated ED patient.