Clinical outcomes of a remimazolam-based sedation regimen in patients receiving ECMO: a retrospective comparative study

Objective Recent meta-analyses have established the overall safety of remimazolam in general surgical populations, but evidence in high-risk subgroups such as patients requiring extracorporeal membrane oxygenation (ECMO) remains absent. This study aimed to compare the sedative effects of remimazolam-based vs. midazolam-based sedation regimens in adults requiring ECMO, with a focus on the incidence of delirium. Methods This single-center retrospective study included patients receiving ECMO from January 2023 to October 2025. The primary analysis cohort comprised patients receiving veno-arterial ECMO (VA-ECMO, n = 44), divided into a remimazolam group (Group R , n = 22) or a midazolam group (Group M, n = 22). The primary outcome was delirium incidence assessed by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Results For the primary outcome, delirium occurred in 0/22 (0%) patients in Group R vs. 6/22 (27.3%) in Group M (risk difference −27.3%, 95% CI −45.9% to −8.7%, p = 0.021 by Fisher's exact test). Due to zero events in Group R, Firth's penalized likelihood regression adjusting for Acute Physiology and Chronic Health Evaluation II (APACHE-II) yielded an odds ratio of 0.06 (95% CI 0.00 to 0.56, p = 0.009), and multivariable and propensity score adjustments produced consistent results. E-value analysis (point estimate 2.0, lower CI bound 1.3) indicated that a relatively modest unmeasured confounder could potentially shift the confidence interval to include the null. For secondary outcomes, Group R had shorter recovery time after decannulation (24.90 ± 3.36 h vs. 29.84 ± 4.53 h, p < 0.001), better-preserved muscle strength (median MRC grade 1 vs. 0, p < 0.001), and lower incidences of hypotension and bradycardia (both p < 0.05). Conclusion In this retrospective exploratory study, a remimazolam-based sedation regimen was associated with lower delirium incidence, faster recovery, and better-preserved muscle strength compared with a midazolam-based regimen. These findings reflect a comparison of two distinct sedation regimens rather than a head-to-head drug comparison of remimazolam vs. midazolam. These hypothesis-generating findings warrant further validation in prospective studies.