Background:We conducted a randomized trial to evaluate the efficacy and safety of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy. Methods:From June 2012 to July 2014, 150 patients with delayed extubation after craniotomy were randomized 1:1 and were assigned to the dexmedetomidine group that received a continuous infusion of 0.6 mg/kg/h (10 mg/mL) or the control group that received a maintenance infusion of 0.9% sodium chloride for injection. The mean percentage of time under optimal sedation (SAS3-4), the percentage of patients who required rescue with propofol/fentanyl, and the total dose of propofol/ fentanyl required throughout the course of drug infusion, as well as VAS, HR, MAP, and SpO(2) were recorded. Results:The percentage of time under optimal sedation was significantly higher in the dexmedetomidine group than in the control group (98.4% +/- 6.7% vs. 93.0% +/- 16.2%, P=0.008). The VAS was significantly lower in the dexmedetomidine group than in the control group (1.0 vs. 4.0, P=0.000). The HR and mean BP were significantly lower in the dexmedetomidine group than in the control group at all 3 time points (before endotracheal suctioning, immediately after extubation, and 30min after extubation). No significant difference in SpO(2) was observed between the 2 groups. For hemodynamic adverse events, patients in the dexmedetomidine group were more likely to develop bradycardia (5.3% vs. 0%, P=0.043) but had a lower likelihood of tachycardia (2.7% vs. 18.7%, P=0.002). Conclusions:Dexmedetomidine may be an effective prophylactic agent to induce sedation and analgesia in patients with delayed extubation after craniotomy. The use of dexmedetomidine (0.6 mg/kg/h) infusion does not produce respiratory depression, but may increase the incidence of bradycardia.