“Accordingly, dexmedetomidine may provide clinically relevant benefits compared with standard sedation, even when measures to reduce the risks of oversedation are implemented,” the authors comment.
Dr. Jukka Takala, at Bern University Hospital, Switzerland and colleagues point out that benzodiazepines and propofol are problematic for long-term sedation, and that dexmedetomidine may have advantages in this setting. They conducted two multicenter randomized trials of dexmedetomidine in mechanically ventilated adult ICU patients – one comparing it to midazolam in 500 patients, and the other comparing dexmedetomidine to propofol in 500 other patients.
The main outcome measures in both trials were the proportion of time at target sedation levels and duration of mechanical ventilation.
The dexmedetomidine/midazolam ratio in time at target sedation was 1.07 and the dexmedetomidine/propofol ratio was 1.00, the investigators report – demonstrating noninferiority of dexmedetomidine in this regard.
While median duration of ventilation was significantly shorter with dexmedetomidine (123 hours) than midazolam (164 hours; p=0.03), the difference was not significant with dexmedetomidine (97 hours) vs propofol (118 hours; p=0.24), the authors report. However, the difference in time to extubation favored dexmedetomidine in both trials: 147 hours for midazolam vs 101 hours for dexmedetomidine, (p=0.01), and 93 hours for propofol vs 69 hours for dexmedetomidine (p=0.04)
As secondary measures, “Patients receiving dexmedetomidine were more arousable, more cooperative, and better able to communicate their pain than patients receiving either midazolam or propofol,” the report indicates.
Overall, dexmedetomidine was associated more adverse effects. For example, comparing dexmedetomidine with midazolam, rates of hypotension were higher (20.6% vs 11.6%; p=0.007) as was the incidence of bradycardia (14.2% vs 5.2%; p=0.001).
“We conclude,” write Dr. Takala and colleagues, “that dexmedetomidine is feasible for long-term sedation in intensive care patients and may provide clinically relevant benefits by reducing the duration of invasive ventilation and improving comfort.”
In an editorial, Dr. Hannah Wunsch, with Columbia University in New York, notes that dexmedetomidine was approved in 1999 for sedation of ventilated patients. One reason it is not more widely used, she explains, is cost.
“Dexmedetomidine is substantially more expensive than off-patent sedatives, such as propofol and midazolam (median per-patient drug acquisition cost was reported as $1166 for dexmedetomidine vs $60 for midazolam in one study),” she notes.
However, dexmedetomidine comes off patent in 2013 in the US. “When there is no longer a need to weigh the drug acquisition costs, even uncertain improvements in the patient experience should be justification enough for broader use of dexmedetomidine in the ICU,” Dr. Wunsch concludes.
JAMA. 2012;307(11):1151-1160, 1195-1197.