Direct adaptive disturbance rejection control for sedation and analgesia

Patient care in intensive care units involves the combined administration of several drugs. Apart from the desired drug effect, often such drugs disturb other physiological functions of the patient. Control strategies based on nominal pharmacokinetic models cannot ideally embody interpatient and intrapatient variability. Moreover, exogenous and endogenous disturbances also alter physiological parameters of the patient which in turn affect the pharmacokinetics and phar-macodynamics of drugs. Such parameter variations directly influence the output drug effect. Thus, a direct adaptive controller that updates control gains in accordance to system uncertainty and system disturbances can account for interpatient and intrapatient variability. This paper proposes a direct adaptive disturbance rejection controller for the continuous infusion of multiple drugs that have interactive effects. As a case study, we investigate the closed-loop control of propofol infusion while considering the synergistic effect of remifentanil.