A target trial emulation of dexmedetomidine to treat agitation in the intensive care unit

Abstract

Objective: Agitation is a major problem in the intensive care unit. However, no treatment has clearly emerged as effective and safe. Using target trial emulation, we aimed to test the hypothesis that early intervention with dexmedetomidine would accelerate agitation resolution. Methods: We read clinical notes in an electronic medical records system with natural language processing to identify patients with agitation. We obtained their demographics, trajectories, associations, and outcomes. We used g-formulas to study the possible effects of dexmedetomidine on agitation resolution and key outcomes. Results: We screened 7525 patients. Overall, 2242 patients (29.8%) developed within-intensive care unit agitation, and 2052 (27.3%) were eligible for inclusion in the target trial emulation, with 314 treated with dexmedetomidine. Dexmedetomidine-treated patients had more severe illness and were more likely to have unplanned emergency admissions with medical diagnoses. However, they achieved higher rates of resolution of within-intensive care unit agitation (94% versus 72%; p < 0.001) and lower 30-day mortality (5% versus 9%; p = 0.033). Early initiation of dexmedetomidine accelerated the resolution of agitation (risk ratio [RR] 1.13 [95%CI 1.03-1.21]; risk difference [RD] 9.8% [95%CI 2.6%-15.4%]); extubation by Day 30 (RR 1.03 [95%CI 1.02-1.04]; RD 3.1% [95%CI 2.2%-4.2%]); and reduced the chance of having a tracheostomy by Day 30 (RR 0.67 [95%CI 0.34-0.99]; RD-3.5% [95%CI-7.0%--0.0%]) Conclusion: Through target trial emulation analysis, early dexmedetomidine was associated with an increased rate of resolution of agitation and extubation and decreased tracheostomy risk.