Changes in the plasma protein‐binding rate of remifentanil during cardiopulmonary bypass

Abstract Aims Cardiopulmonary bypass (CPB) reduces the plasma protein‐binding rate of some anaesthetics and can enhance their pharmacological effects by increasing the unbound drug fraction. However, whether these changes occur with remifentanil remains to be explored. We investigated the changes in the protein‐binding rate of remifentanil during CPB compared with propofol. Methods Thirteen patients (≥18 years old) who were scheduled to undergo cardiovascular surgery with CPB were included. Arterial blood samples were collected to measure the plasma concentrations of remifentanil and propofol before CPB (T1), 30 (T2) and 60 (T3) minutes after the start of CPB, and 30 min after CPB discontinuation (T4). The samples were immediately centrifuged to separate the plasma after blood collection. Equilibrium dialysis was used to separate the unbound fraction. The remifentanil and propofol concentrations were measured by liquid chromatography‐mass spectrometry. The protein‐binding rate was calculated based on the total and unbound fraction of each drug. Results The remifentanil protein‐binding rates at each time point were 27.9% ± 11.2% (T1), 13.5% ± 4.4% (T2), 14.0% ± 3.3% (T3) and 24.5% ± 6.9% (T4). The propofol protein‐binding rates were 97.5% ± 0.7% (n = 4; T1), 95.8% ± 1.4% (T2), 95.3% ± 1.3% (T3) and 95.8% ± 1.1% (T4). The protein binding rates of both drugs decreased during CPB and reversed after CPB. The change in the unbound fraction was 1.2‐fold for remifentanil and 1.7‐1.9‐fold for propofol. Conclusions Unlike propofol, remifentanil might not demonstrate significantly enhanced pharmacological effects during CPB.