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Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation with Sepsis: A Randomized Clinical Trial
Kawazoe Y, Miyamoto K, Morimoto T, et al. JAMA. 2017; 317: 1321-8.
Study Question: Does dexmedetomidine (DEX) affect 28-day mortality and ventilator-free days in patients with sepsis on mechanical ventilation (MV)?
Study Description: This was a randomized, multicenter, open-label trial comparing DEX to non-DEX sedatives, including propofol and midazolam (and/or fentanyl). Adult patients with sepsis requiring MV (invasive and non-invasive) for at least 24 hours were included. The co-primary outcomes were 28-day mortality and ventilator-free days.
Results: The study included 201 patients over a 3 year time-frame. Baseline demographics were comparable between the groups. There were no differences in 28-day mortality (19% vs. 28%; p=0.14) or median ventilator-free days (20, IQR 5-24 vs. 18, IQR 0.5-23; p=0.20) between the DEX and non-DEX groups, respectively. There were no differences in any secondary outcomes. The rate of well-controlled sedation was significantly higher in the DEX group (range 17% - 58% vs. 20% - 39%; p=0.01). The total amounts of propofol and midazolam were significant lower in the DEX group.
Conclusion(s): Sedation using DEX does not improve 28-day mortality or ventilator-free days as compared to non-DEX sedatives in patients with sepsis requiring MV.
Perspective: Although this trial did not verify the findings of the subgroup analysis from the MENDS trial, there are some key distinctions worth noting. The MENDS trial included patients on MV who received either DEX versus lorazepam with DEX doses being much lower in the current trial (maximum of 0.7 mcg/kg/hr). The current study also included patients that were older and had lower APACHE II scores.
Although not found to be statistically significant, a 9% reduction in 28-day mortality may still pose clinical importance. The possibility of being underpowered is high given that the power analysis required a 20% difference between the groups. The lack of statistical difference may also be confounded and a result of sedation, spontaneous breathing trials, ventilator-weaning, and early physical therapy protocols, which were part of routine clinical practice. Further research is warranted to assess the interplay of preferred agents and/or protocols on short- and long-term mortality.