Alterations in Total and Unbound Remimazolam Concentrations During Cardiac Surgery Requiring Cardiopulmonary Bypass:...

To monitor temporal changes in total and unbound remimazolam concentrations during cardiac surgery requiring cardiopulmonary bypass (CPB).

Single-center, prospective, observational study.

Operating rooms of a university hospital.

Adult patients aged ≥20 years, weighing ≤90 kg, undergoing elective cardiac surgery with CPB.

Remimazolam was initiated at 12 mg·kg⁻¹·h⁻¹ until loss of responsiveness to verbal stimuli and then maintained at 1 mg·kg⁻¹·h⁻¹ throughout surgery.

Blood samples were collected at eight time points (T1-T8). Concentrations measured at the end of anesthetic induction (T1) and immediately after CPB initiation (T3) were analyzed, with T1 defined as the baseline. Total and unbound concentrations were quantified using ultrahigh-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The Wilcoxon signed-rank test was used to compare total and unbound concentrations between baseline (T1) and each subsequent time point (T2-T8). The total concentration at T3 was significantly lower than that at T1 (median: 761 ng·mL⁻¹ v 560 ng·mL⁻¹; p < 0.001), whereas the unbound concentration at T3 was significantly higher (median: 7.1 ng·mL⁻¹ v 23.5 ng·mL⁻¹; p < 0.001). Although the unbound concentration gradually declined thereafter, it remained elevated above the baseline throughout surgery.

An increase in unbound concentration and a transient decrease in total concentration occurred at CPB initiation. Under the present dosing protocol, unbound remimazolam concentrations remained elevated throughout surgery.