BACKGROUND: Agitated delirium frequently poses management challenges in palliative care. Interventions are needed to manage delirium yet allow meaningful end-of-life communication. Dexmedetomidine can provide wakeful sedation and may fill this therapeutic need. Our objectives were to study the safety and efficacy of using dexmedetomidine in inpatients with agitated delirium. METHODS: In a prospective study, ten adult patients received a dexmedetomidine infusion for agitated delirium in the Bruyère Health inpatient Palliative Care Unit. Following the introduction of an approved subcutaneous dexmedetomidine protocol, doses (range, 0.2-0.7 mcg/kg/h) were titrated to achieve wakeful sedation, targeting a Richmond Agitation-Sedation Scale Palliative version (RASS-PAL) level of -1 to +1. RESULTS: Seventy percent (7/10), 50% (4/8), and 83% (5/6) of patients achieved the RASS-PAL target sedation level at least once per day on Days 1, 2, and 3 of dexmedetomidine infusion, respectively. Those who did not consistently achieve target sedation typically died in less than 3 days. Most patients (n=7) received a maximum dexmedetomidine dose of 0.4-0.5 mcg/kg/h. Dexmedetomidine was discontinued prior to death in five cases due to perceived ineffectiveness (n=1), family requesting deeper sedation (n=1), asymptomatic hypotension (n=2), or bradycardia (n=1). In patients with transient hypotension or bradycardia, death occurred 19 h to 18 days following dexmedetomidine discontinuation. CONCLUSIONS: Subcutaneous dexmedetomidine infusion may be a safe and effective way of providing wakeful sedation for patients with agitated delirium in palliative care. However, prospective, controlled studies with standardized approaches to co-sedative and analgesia management are needed to better determine efficacy, adverse effects, and inform patient selection.