Changes in Free and Total Remimazolam Concentrations During Cardiopulmonary Bypass: A Randomized Dose-Comparison Trial.

In 30 seconds

This randomized, controlled, parallel-group trial studied 36 adults undergoing cardiac surgery with cardiopulmonary bypass (CPB), comparing remimazolam at 1 mg/kg/h with a reduction to 0.7 mg/kg/h at CPB initiation. Free remimazolam concentrations increased over time with the unchanged infusion but remained stable after dose reduction; the time-by-group interaction was significant (p interaction = 0.001). The largest adjusted between-group difference occurred 30 minutes after CPB termination (mean difference [95% CI], 89 [58-120] ng/mL; p < 0.001). Bispectral index values were not linearly associated with free or total concentrations.

Key findings

• Free remimazolam increased over time with the 1 mg/kg/h infusion, while concentrations remained stable after reduction to 0.7 mg/kg/h at CPB initiation.
• The time-by-group interaction for baseline-adjusted free concentrations was significant (p interaction = 0.001).
• At 30 minutes after CPB termination, the largest adjusted between-group difference was 89 [58-120] ng/mL (p < 0.001).
• Bispectral index values showed no linear association with free or total remimazolam concentrations.

Why it matters

CPB-related changes may alter free remimazolam concentrations even when infusion is unchanged, while bispectral index values did not track those concentrations in this trial. The findings highlight a potential mismatch between administered dose, pharmacologically active drug levels, and this monitoring measure during bypass, and provide evidence about a dose-adjustment strategy in this setting.

What to keep in mind

The trial included 36 adults at a university hospital; the abstract does not report clinical outcomes beyond drug concentrations and bispectral index associations.