Nashville, TN—Dexmedetomidine and propofol were equally effective for light sedation of mechanically ventilated adults and led to similar outcomes, according to a new study.

The increased use of mechanical ventilation during the COVID-19 pandemic has put extra focus on sedative medications used in intensive care because they are associated with increased delirium. That can lead to higher mortality rates and ICU-related dementia, as well as higher medical costs.

The report in the New England Journal of Medicine gave the most definitive answer yet to which of the drugs is safer or more effective.

The Vanderbilt University Medical Center–led, double-blinded, randomized, controlled trial enrolled 422 mechanically ventilated adults at 13 U.S. medical centers. The patients, all of whom had sepsis, were placed on ventilators and almost evenly divided between the two sedatives.

“We found very similar patient outcomes with the two drugs for brain function, ventilator times and death. From a critical care outcomes perspective, our results show that these two sedatives are equally effective when performing up-to-date ICU care,” said study coleader Christopher Hughes, MD, professor of anesthesiology.

While clinical guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation, the authors point out that the two sedatives differ in arousability, immunity, and inflammation. They sought to determine if that meant a difference in outcomes.

The 422 patients were randomly assigned to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation–Sedation Scale (RASS, on which scores range from −5 [unresponsive] to +4 [combative]). The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0).

Defined as the primary end point was days alive without delirium or coma during the 14-day intervention period, while secondary end points included ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.

The authors report that they essentially found no difference between dexmedetomidine and propofol. Specifically, here is what they determined:
• During the 14 days from the start of mechanical ventilation, the median total days alive without delirium or coma was 10.7 in the dexmedetomidine group, 10.8 in the propofol group.
• During the 28 days from the start of ventilation, the median of ventilator-free days was 23.7 in the dexmedetomidine group, 24.0 in the propofol group.
• Death occurred within 90 days for 38% of those who had received dexmedetomidine and 39% of those who had received propofol.
• The median cognitive status score at 6 months was 40.9 in the dexmedetomidine group and 41.4 in the propofol group, although researchers note that, in both drug groups, at 6 months following their illness, approximately one in four patients appeared to exhibit clinically important cognitive dysfunction, with cognitive scores two standard deviations below population norms.

“For this critical care application, statistically speaking, there’s nothing in our results to distinguish the safety and patient outcome profiles of these two drugs,” colead researcher Pratik Pandharipande, MD, said.

Dexmedetomidine, the newer of the sedative drugs, didn’t support better patient outcomes, even though it is known to have advantages such as better sleep and better anti-inflammatory properties, the authors reveal.

“Our findings [...] strongly reinforce current guidelines recommending either dexmedetomidine or propofol use for light sedation when continuous sedation is needed for adults requiring mechanical ventilation, with or without sepsis,” the authors write, concluding, “Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol.”

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
 « Click here to return to Weekly News Update.