麻豆传媒

Among mechanically ventilated adults with sepsis being treated with light sedation, no differences were observed between dexmedetomidine, an alpha-2 receptor agonist, and propofol, a randomized trial found.

There was no difference in days alive without delirium or coma between patients treated with dexmedetomidine versus propofol at 14 days (adjusted median 10.7 vs 10.8 days; OR 0.96, 95% CI 0.74-1.26), reported Christopher Hughes, MD, of Vanderbilt University Medical Center in Nashville, and colleagues.

Moreover, there were no differences between groups in ventilator-free days at 28 days (adjusted median 23.7 vs 24.0 days; OR 0.98, 95% CI 0.63-1.51), nor death at 90 days (38% vs 39%; HR 1.06, 95% CI 0.74-1.52).

These results were presented at the virtual Society of Critical Care Medicine's (SCCM) Critical Care Congress, and published simultaneously in the .

During the presentation, Hughes noted that prior studies showed improvement with dexmedetomidine compared with lorazepam and midazolam with regard to delirium, coma, time receiving mechanical ventilation, and cost, though noninferiority studies found no significant impact on duration of mechanical ventilation, length of stay, or short-term mortality.

Researchers said SCCM recommends sedation with either light levels of dexmedetomidine or propofol for adults receiving mechanical ventilation and continuous sedation. The authors noted that dexmedetomidine has anti-inflammatory and bacterial properties superior to gamma-aminobutyric acid (GABA) agonists such as propofol and "reduces neuronal apoptosis and promotes biomimetic sleep," which could improve clinical outcomes.

Hughes also reported lower rates of subsequent infection versus midazolam and reduced 28-day mortality in sepsis patients versus lorazepam.

The (MENDS2) trial examined mechanically ventilated adults with sepsis at 13 medical centers from May 2013 to December 2018. They were randomized to receive either dexmedetomidine or propofol. Participants were eligible if they were admitted to a medical or surgical ICU, had suspected or known infection, and were treated with continuous sedation for invasive mechanical ventilation.

The primary outcome was days alive without delirium or coma during the 14-day intervention. Delirium was assessed via the (RASS), with a score ranging from -5 (unresponsive) to +4 (combative).

Overall, 422 patients were assigned to a trial drug. During the presentation, Hughes said that bedside nurses obscured treatment from clinicians by covering the IV bag and intravenous tubing with black coverings prior to clinicians entering patient rooms.

Median receipt of trial drugs was 3 days, and median RASS score was -2.0.

A secondary endpoint was age-adjusted total score on the Telephone Interview for Cognitive Status (TICS-T) at 6 months, and there was no difference between groups (adjusted median score 40.9 vs 41.4; OR 0.94, 95% CI 0.66-1.33). Safety was also comparable between groups, with similar proportions of patients with organ dysfunction, hypotension, or severe lactic acidosis, as well as symptomatic bradycardia.

Fewer patients in the dexmedetomidine group had acute respiratory distress syndrome (ARDS) or signs of trial drug withdrawal, and fewer patients in the propofol group extubated themselves, the authors noted.

Limitations to the data include unmasking of group assignment in 14% of patients, as well as some cross-contamination of sedative use. Researchers also had a slower than anticipated enrollment, requiring an adjustment of the sample size, though they said they had "adequate power to study the questions of interest."

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