Effects of different sedation regimens on delirium in ICU patients.

Background: Delirium is common among ICU patients and worsens outcomes. The comparative effectiveness of sedatives remains uncertain. Methods: We conducted a single-center, prospective cohort study using a prespecified 48-h landmark. Adults (≥18 years) with an expected ICU stay ≥24 h and continuous intravenous sedation ≥6 h were enrolled. The predominant sedative used during the first 48 h (dexmedetomidine, midazolam, or remimazolam) was recorded. Predominance was defined Results: Of the 506 patients who were screened, 426 were included in the landmark cohort (dexmedetomidine = 162, midazolam = 192, and remimazolam = 72). Incident delirium occurred in 108 (25.4%) of the 426 patients. After overlap weighting, dexmedetomidine was associated with a lower risk of delirium versus midazolam (RR 0.70, 95% CI 0.52-0.92) and a similar, although not significant, pattern versus remimazolam (RR 0.74, 95% CI 0.52-1.03). Dexmedetomidine had a higher time-in-target sedation and more ventilator-free days, with more bradycardia, but no apparent increase in hypotension or hypertension. Mortality did not differ. The findings were directionally consistent in the time-varying analysis (HR 0.76, 95% CI 0.58-0.99). Conclusion: In this prospective cohort, dexmedetomidine-predominant sedation was associated with a lower risk of post-landmark delirium and better sedation quality than midazolam, at the cost of more bradycardia and without differences in mortality. These findings warrant multicenter confirmation and randomized evaluation.