Critically ill patients often require the administration of sedation therapy to reduce discomfort from care interventions and optimize mechanical ventilation.1 Despite these perceived advantages, long-term sedation therapy with agents such as midazolam and propofol can have deleterious effects (e.g., prolonged mechanical ventilation, coma, delirium, etc.). Studies have suggested that dexmedetomidine, an α-2 agonist, may improve patient safety and reduce the incidence of delirium and duration of mechanical ventilation when compared to propofol and benzodiazepines in the intensive care unit (ICU).2,3
A study recently published sought to compare the efficacy of dexmedetomidine vs. midazolam or propofol in maintaining sedation, reducing duration of mechanical ventilation and improving patients’ interaction with nursing care. The study consist of two-multicenter, randomized, double-blind trials that included mechanically ventilated patients who needed light to moderate sedation for more than 24 hours.4 The MIDEX trial compared midazolam (n=251) with dexmedetomidine (n=249) in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol (n=247) with dexmedetomidine (n=251) in 31 centers in 6 European countries and 2 centers in Russia. Daily awakening trials and spontaneous breathing trials were implemented in both studies.
The authors determined that the median duration of mechanical ventilation was shorter in the dexmedetomidine group compared to patients receiving midazolam (123 hours [67-337]) vs. (164 hours [92-380]; p=.03) but was not different when dexmedetomidine was compared to propofol (97 hours [45-257]) vs. (118 hours [48-327]; p=.24). Patients’ interaction (measured using visual analogue scale) was improved with dexmedetomidine when compared to both midazolam and propofol (p< 0.001). Length of ICU and hospital stay and mortality were similar. Moreover, patients receiving dexmedetomidine when compared to midazolam developed more hypotension ([20.6%] vs. [11.6%]; p=0.007) and bradycardia ([14.2%] vs. [5.2%]; p<0.001).
Despite that these two RCTs provide important evidence that dexmedetomidine is an effective sedative compared with both midazolam and propofol, and its use may be associated with decreased time to extubation, easier communication with patients, consideration of the high cost and expense may preclude its use given the lack of concrete long-term outcome data.
1. Wunsch H, Kahn JM, Kramer AA, et al. Use of intravenous infusion sedation among mechanically ventilated patients in the United States. Crit Care Med 2009 Dec;37(12):3031-9.
2. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs. lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653.
3. Ruokonen E, Parviainen I, Jakob SM, et al. “Dexmedetomidine for Continuous Sedation” Investigators. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009;35(2):282-290.
4. Jakob SM, Ruokonen E, Grounds MR, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151-1160.