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Safety and acceptability of sedative selfadministration by patients receiving mechanical ventilation is unknown.To determine if self-administration of dexmedetomidine by patients is safe and acceptable for selfmanagement of anxiety during ventilatory support.In a pilot trial in 3 intensive care units, 17 intubated patients were randomly assigned to dexmedetomidine and 20 to usual care. Dexmedetomidine was administered via standard pumps for patient-controlled analgesia, with a basal infusion (0.1–0.7 μg/kg per hour) titrated by the number of patient-triggered doses (0.25 μg/kg per dose). Safety goals were heart rate greater than 40/min, systolic blood pressure greater than 80 mm Hg, and diastolic blood pressure greater than 50 mm Hg. Acceptability was based on patients’ self-reported satisfaction and ability to administer the sedative. A 100-mm visual analog scale was used daily to assess patients’ anxiety.The sample was 59% male and 89% white. Mean values were age, 50.6 years; score on the Acute Physiology and Chronic Health Evaluation, 60.1; and protocol duration, 3.4 days. Five dexmedetomidine patients had blood pressure and/or heart rate lower than safety parameters, necessitating short-term treatment. Nurses’ adherence to reporting of safety parameters was 100%; adherence to the dexmedetomidine titration algorithm was 73%. Overall baseline anxiety score was 38.4 and did not change significantly (βday = 2.1; SE, 2.5; P = .40). Most dexmedetomidine patients (92%) were satisfied or very satisfied with their ability to self-administer medication.For select patients, self-administration of dexmedetomidine is safe and acceptable.