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

Area of Science:

• Anesthesiology
• Pharmacology
• Cardiovascular Surgery

Background:

• Remimazolam is used in cardiac surgery for hemodynamic stability.
• Cardiopulmonary bypass (CPB) may alter remimazolam's free fraction due to hemodilution and hypoalbuminemia.
• The impact of CPB on free remimazolam concentrations requires further investigation.

Purpose of the Study:

• To investigate the temporal profile of free remimazolam concentrations during CPB.
• To determine if a pragmatic dose adjustment can maintain stable free remimazolam levels.
• To assess the safety and efficacy of adjusted remimazolam dosing during CPB.

Main Methods:

• A randomized, controlled, parallel-group trial was conducted at a university hospital.
• Thirty-six adult patients undergoing cardiac surgery with CPB were enrolled.
• Patients received either a normal dose (1 mg/kg/h) or a reduced dose (0.7 mg/kg/h) of remimazolam during CPB.

Main Results:

• Free remimazolam concentrations increased over time in the normal-dose group but remained stable in the low-dose group (p_interaction = 0.001).
• A significant difference in free remimazolam was observed post-CPB (mean difference [95% CI], 89 [58-120] ng/mL; p < 0.001).
• No correlation was found between bispectral index values and remimazolam concentrations.

Conclusions:

• Constant remimazolam infusion during CPB leads to increasing free concentrations.
• Reducing the remimazolam infusion rate to 70% at CPB initiation effectively stabilizes free concentrations.
• This dose adjustment strategy may prevent remimazolam overexposure during CPB in cardiac surgery.