Related Experiment Video
Updated: Aug 6, 2026
A Recovery Cardiopulmonary Bypass Model Without Transfusion or Inotropic Agents in Rats
Published on: March 23, 2018
Changes in Free and Total Remimazolam Concentrations During Cardiopulmonary Bypass: A Randomized Dose-Comparison
Sho Ohno1, Yusuke Yoshikawa1, Daiki Kurihara2
1Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Objectives:
Remimazolam is increasingly used in cardiac surgery for hemodynamic stability; however, during cardiopulmonary bypass (CPB), hemodilution and hypoalbuminemia may increase its pharmacologically active free fraction, raising concern about unrecognized overexposure under constant infusion. Yet, the temporal profile of free remimazolam during CPB has not been fully elucidated. We investigated whether a pragmatic dose adjustment could maintain free remimazolam concentrations within a stable range.
Design:
Randomized, controlled, parallel-group trial.
Setting:
A university hospital.
Participants:
Thirty-six adults undergoing cardiac surgery with CPB.
Interventions:
Patients were assigned to a normal-dose group (1 mg/kg/h) or a low-dose group in which the infusion rate of remimazolam was reduced to 70% at CPB initiation (0.7 mg/kg/h).
Measurements And Main Results:
The primary outcome was free remimazolam concentration. Secondary outcomes included total remimazolam concentration, protein binding, and associations between bispectral index values and drug concentrations. Baseline-adjusted analysis of free remimazolam concentrations showed a significant time-by-group interaction (pinteraction = 0.001), increasing over time in the normal-dose group but remaining stable in the low-dose group. The largest adjusted between-group difference was observed 30 minutes after CPB termination (mean difference [95% CI], 89 [58-120] ng/mL; p < 0.001). No linear association was observed between bispectral index values and free or total remimazolam concentrations.
Conclusion:
During CPB, free remimazolam concentrations increased over time under constant infusion without corresponding changes in bispectral index values, whereas reducing the infusion rate to 70% at CPB initiation maintained free remimazolam concentrations within a stable range.
Insights
During cardiopulmonary bypass (CPB), free remimazolam levels increase with standard infusion. Reducing the remimazolam dose by 30% at CPB initiation stabilizes these levels, preventing potential overexposure in cardiac surgery patients.
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 (pinteraction = 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.
