Modelling of Blood Loss Influence on Propofol Concentrations and Anesthetic States in Critical Responses

This work studies the classical pharmacokinetic-pharmacodynamic (PK-PD) model of Propofol for total intravenous anesthesia in response to intraoperative blood loss. Anesthetic and hemodynamic stability are impaired in the setting of trauma surgeries or major procedures with high hemorrhage risk. Blood loss has immediate effects on the cardiovascular system, but also affects the plasma concentration of the perioperatively infused drugs. During perioperative transition periods, when fast blood losses occur, the PK models on which the target-controlled infusion (TCI) is based should be updated. Then, the population-based parameters move towards an individualized strategy that accounts also for the actual blood volume in the patient. This paper evaluates the influence of changing blood volume on the PK model of Propofol, hence on the anesthesia state of the patient. The simulations also account for the hemodynamic responses due to the conflicting interactions of both hemorrhage and anesthetic drug infusion. This model has great potential for inclusion in multiple-closed loop control strategies of anesthesia-hemodynamic states, as it is simple and adapted from well-known PK models, for which control strategies are already mature.