Anesthetic Management Considerations During Cardiopulmonary Bypass
Volatile Anesthetics
End-tidal sevoflurane concentrations can be used as a reliable surrogate for plasma levels and may guide anesthetic depth during CPB. High concentrations of sevoflurane or isoflurane that produce burst suppression should be avoided, as burst suppression may impair cerebral blood flow autoregulation and increase neurologic risk.
Fentanyl and Sufentanil
An additional opioid bolus before initiation of CPB may help blunt the abrupt decline in plasma concentration that occurs with bypass onset. This strategy should be balanced carefully, as hemodilution during CPB can increase the free fraction of opioids. If an extra bolus is administered, dose reduction should be considered to avoid excessive sedation when pulmonary blood flow is restored and redistribution occurs later in the case.
Remifentanil
Because remifentanil clearance is reduced during hypothermia, infusion rates should be decreased by approximately 30 percent for every 5°C reduction in core temperature to maintain stable plasma levels. Conversely, the increased volume of distribution associated with CPB may necessitate higher initial dosing or adjusted maintenance rates in normothermic patients to ensure adequate analgesia.
Alfentanil
At CPB initiation, alfentanil demonstrates a reduction in total plasma concentration with a concurrent increase in the unbound fraction. Given these opposing effects, maintaining a constant infusion rate throughout CPB without dose adjustment appears appropriate.
Recommendations for Further Research
Future investigations should account for the confounding effects of coadministered anesthetic and vasoactive agents when analyzing plasma drug concentrations. Larger, sex-balanced, and weight-matched study populations are needed to clarify clinically relevant differences, including potential sex-specific pharmacokinetic and pharmacodynamic effects. Comparative studies involving age-matched male and postmenopausal female patients may help isolate hormonal and physiologic contributors.
Standardization of CPB priming volumes, depth-of-anesthesia monitoring, and hemodynamic targets would improve interpretability across studies. The pharmacology of midazolam during on-pump cardiac surgery remains underreported and warrants focused evaluation. Additionally, anesthetic drug behavior during extracorporeal membrane oxygenation in critically ill patients represents an important and largely unexplored area.
Conclusions
Management of anesthetic pharmacokinetics during CPB remains complex and requires individualized strategies informed by physiologic changes, temperature, and circuit-related drug sequestration. Current practice relies on processed electroencephalogram monitoring, careful dose adjustments, and thoughtful anesthetic selection to mitigate these challenges. Although intraoperative awareness remains uncommon, its continued occurrence reinforces the importance of understanding drug behavior during bypass.
Key priorities include individualized dosing, objective depth-of-anesthesia monitoring, and anticipation of CPB-related alterations in drug distribution and clearance. Substantial knowledge gaps persist regarding optimal anesthetic concentrations, the impact of modern CPB techniques, sex-specific responses, and long-term neurologic outcomes. Addressing these gaps offers an opportunity to improve safety, precision, and outcomes in cardiac anesthesia.