1. Treatment with dexmedetomidine was shown not to differ from propofol treatment in adult patients with sepsis who were under mechanical ventilation.
2. No significant difference was found in functional, quality-of-life, or cognitive assessment scores between the two treatment methods.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Sedative medications are often administered in mechanically ventilated adults with sepsis for patient comfort and safety; however, they may potentiate acute brain dysfunction. Dexmedetomidine, an alpha-2 receptor agonist, has anti-inflammatory and bacterial clearance properties that are superior to GABA agonists, such as propofol, which could improve clinical outcomes. As such, this trial evaluated whether dexmedetomidine leads to better short-term and long-term outcomes compared to propofol in mechanically ventilated patients with sepsis. The study determined no significant difference in the number of calendar days alive without delirium or coma during the intervention between the two treatment groups. Furthermore, no significant difference was found in key secondary outcomes such as cognition, quality-of-life, or function assessment scores between the two treatment groups. Study limitations included variability in sedation targets set by clinicians and episodes of unmasking and crossover during the trial. Nonetheless, this study’s results are significant and strongly reinforce current guidelines which recommend the use of either dexmedetomidine or propofol for light sedation in this patient population.
Click to read the study in NEJM
Relevant Reading: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials
In-Depth [randomized controlled trial]: This double-blind, randomized controlled trial enrolled 432 patients. Patients included in the study were treated with continuous sedation for invasive mechanical ventilation and suspected of known infection. Patients with a baseline severe cognitive impairment, pregnant or breastfeeding, and understand approved languages were excluded from the study. The patients were randomized in a 1:1 ratio to receive either dexmedetomidine or propofol, respectively. The primary endpoint was the number of calendar days alive without delirium or coma during the 14 days of intervention. No significant difference was found in the primary outcome between the dexmedetomidine group (adjusted median, 10.7 days; 95% confidence interval [CI], 8.5 to 12.5) and the propofol group (adjusted median, 10.8 days; 95% CI, 8.7 to 12.6) (odds ratio, 0.96; 95% CI, 0.74 to 1.26, P = 0.79). Additionally, no significant difference was found in death at 90 days in the dexmedetomidine group (81 patients, 38%) and the propofol group (82 patients, 39%) (hazard ratio, 1.06; 95% CI, 0.74 to 1.52). Key secondary outcomes including cognition, function, and quality of life. No significant difference was observed between the dexmedetomidine and propofol treatment groups in the Telephone Interview for Cognition Status score after six months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI. 0.66 to 1.33). Altogether, this trial shows that there is no difference in outcomes in mechanically ventilated adults with sepsis treated with dexmedetomidine compared to propofol.
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