Pharmacokinetics and Pharmacodynamics of Analgesic and Anesthetic Drugs in Patients During Cardiac Surgery With Cardiopulmonary Bypass: A Narrative Review.

Cardiopulmonary bypass (CPB) impacts pharmacokinetics and -dynamics of drugs used during cardiac surgery. These alterations can lead to changes in drug efficacy resulting in under- or overdosing. This review summarizes current knowledge on the effects of CPB on commonly used intraoperative and continuously administered anesthetics and analgesics. Out of 197 articles initially identified, 22 were included in the final review. The breakdown of studies by main topic was as follows: propofol (9 articles), sevoflurane (4), remifentanil (3), isoflurane (2), fentanyl (2), and sufentanil (2), and alfentanil (1). The initiation of CPB typically results in hemodilution and hypothermia, leading to a decrease in total plasma concentration combined with an increase in unbound plasma concentrations. This phenomenon has varying implications for different drugs: For propofol and sevoflurane, lower doses may be required during CPB to achieve the same anesthetic effect. Fentanyl and sufentanil plasma concentrations decrease by 25% on average at CPB initiation due to an increased volume of distribution, followed by an increase during CPB, with sufentanil, showing an almost 50% increase post-CPB. This implies that an additional bolus before CPB initiation should be considered, followed by a reduction of the maintenance dose to prevent prolonged sedation. Remifentanil plasma concentration decreases at CPB initiation, which implies that higher initial- or adjusted maintenance dose should be considered in normothermic patients. However, under hypothermic conditions, infusion rates should be decreased by 30% for every 5°C decrease in temperature. Alfentanils, total plasma concentration decreases during CPB, while its free fraction remains unaltered, indicating that no further adjustments are necessary. Target-controlled infusion (TCI) models for propofol (Schnider, Marsh, and PGIMER [Postgraduate Institute of Medical Education and Research]) and remifentanil (Minto) were found to be inaccurate in the context of CPB. Based on the included studies, the use of these pharmacokinetic models is not recommended. In conclusion, dosing inaccuracies resulting in adverse events in on-pump cardiac surgery underscore the importance of understanding the pharmacokinetics and -dynamics of anesthetic and analgesic drugs during CPB. The clinical implication of the altered drug responses after CPB remains challenging in this high-risk population. Key takeaways include the necessity of considering patient-specific factors, utilizing objective monitoring tools, and recognizing potential drug alterations due to CPB.