Population pharmacokinetic-pharmacodynamic modeling to quantify haemodynamic effects during anaesthesia
Population pharmacokinetic-pharmacodynamic modeling to quantify haemodynamic effects during anaesthesia
Intraoperative hypotension is increasingly recognized as a cause of postoperative complications. This thesis of Hong Su investigates the dose-exposure-response relationships of anaesthetic drugs on the haemodynamic side effects using pharmacokinetic-pharmacodynamic modelling. Empirical pharmacodynamic models identified synergistic interactions in mean arterial pressure (MAP) and stroke volume index (SVI) between dexmedetomidine and remifentanil.
We established mechanism-based models for propofol and remifentanil, that adapted from existing preclinical frameworks, enabled the characterization of inherent interactions within the cardiovascular system. The mechanism-based haemodynamic interaction model revealed that combined administration of propofol and remifentanil exhibits complex interaction on haemodynamic effects: antagonistic interaction on heart rate (HR), a synergistic interaction on SV and a mixed synergistic antagonistic interaction on MAP that depends on the propofol concentration.
These findings closely aligned with published data, suggesting reliable predictive performance of the model. This work provides critical insight into how anaesthetic drugs and their combinations affect haemodynamic variables, enabling more precise and individualized drug administration. Our model offers a robust framework for quantitatively understanding the mechanisms underlying haemodynamic changes, potentially enabling a transition from reactive management of hypotension to proactive prevention strategies.