OBJECTIVE: To compare the sedative effect and safety of dexmedetomidine and midazolam in the intensive care unit (ICU) patients undergoing ventilator bundle treatment.
METHODS: A prospective single-blind randomized controlled trial (RCT) was conducted. Ninety patients receiving ICU ventilator-assisted therapy and ventilator bundle treatments for more than 3 days in the First Department of Critical Care Medicine of the Second Hospital of Lanzhou University from January 2013 to December 2014 were enrolled. The patients were randomly divided into two groups for sedative treatment. The patients in dexmedetomidine group (n = 42) were given dexmedetomidine 0.2-0.7 μg x kg(-1) x h(-1) to achieve a goal of satisfactory sedation [Richmond agitation-sedation scale (RASS) score 0 to - 2 during the day, and -1 to -3 at night). The patients in midazolam group (n = 48) were given midazolam 2-3 mg intravenously first, and then 0.05 mg x kg(-1) x h(-1) for maintenance. The drug dose was adjusted according to RASS every 4 hours to maintain the appropriate sedation depth. The patients in both groups received continuous intravenous infusion of fentanyl for analgesia. Ventilator bundle treatments included the head of a bed up 30 degrees to 45 degrees, awaken and extubation appraisal, daily use of proton pump inhibitors for peptic ulcer prevention, prevention of deep vein thrombosis (DVT), chlorhexidine mouth nursing, and removal of sputum by suction from subglottic area. When the patients in both groups obtained satisfactory target sedation, daily awakening was conducted, and spontaneous breathing test (SBT) was carried out to determine optional weaning time. When the condition was optimal, weaning was conducted, otherwise ventilator bundle treatments were continued. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), respiratory frequency (RR) were monitored before and 15, 30, 60, 120, 180 minutes after the treatment, and at the moment of extubation and 30 minutes after extubation. The duration of mechanical ventilation, extubation time, length of ICU stay, and the incidence of adverse events were also recorded.
RESULTS: Both dexmedetomidine and midazolam could give rise to sedation with same score of analgesia in patients in both groups, and similar effect of sedation and analgesia could be achieved. Compared with midazolam, dexmedetomidine could significantly reduce the duration of mechanical ventilation (hours: 108.33 ± 21.96 vs. 119.85 ± 20.29, t = -2.586, P = 0.011), earlier extubation time (hours: 112.95 ± 22.20 vs. 128.58 ± 26.18, = -3.031, P = 0.003), length of ICU stay (hours: 149.21 ± 20.47 vs. 163.88 ± 33.59, = -2.457, P = 0.016), the incidence of delirium [9.5% (4/42) vs. 31.2% (15/48 ), χ2 = 6.349, P = 0.012], but it would elevate the incidence of severe hypotension [28.6% (12/42) vs. 8.3% (4/48), χ2 = 6.277, P = 0.012] and severe bradycardia [19.0% (8/42) vs. 8.3% (4/48), χ2 = 2.225, P = 0.136]. Both drugs could lower SBP, DBP, MAP, and HR, and the effect in dexmedetomidine group was more significant from 60 minutes after treatment [SBP (mmHg, 1 mmHg = 0.133 kPa): 113.12 ± 14.42 vs. 124.40 ± 15.79, DBP (mmHg): 69.02 ± 9.62 vs. 76.94 ± 10.41, MAP (mmHg): 83.76 ± 10.50 vs. 92.77 ± 11.87, HR (bpm): 79.19 ± 12.28 vs. 87.42 ± 17.77, P < 0.05 or P < 0.01]. Both sedatives could significantly lower the rate of spontaneous breathing, and the effect of midazolam group was more significant from 60 minutes after treatment compared with dexmedetomidine group (times/min: 18.27 ± 4.29 vs. 20.07 ± 4.11, P < 0.05).
CONCLUSIONS: The sedative effects of dexmedetomidine in the ICU patients treated with ventilator bundle treatment are satisfactory, and it can shorten the duration of mechanical ventilation, extubation time and length of ICU stay, reduce the incidence of delirium. However, monitoring should be strengthened in order to prevented and control the adverse effects such as severe hypotension and severe bradycardia.
