Optimal drug dosing control for intensive care unit sedation using a hybrid deterministic-stochastic pharmacokinetic and pharmacodynamic model

In clinical intensive care unit practice sedative/analgesic agents are titrated to achieve a specific level of sedation. The level of sedation is currently based on clinical scoring systems. Examples include the motor activity assessment scale (MAAS) and the modified Ramsay sedation scale (MRSS). In general, the goal of the clinician is to find the drug dose that maintains the patient at a sedation score corresponding to a moderately sedated state. This is typically done empirically, administering a drug dose that usually is in the effective range for most patients, observing the patient´s response, and then adjusting the dose accordingly. However, the response of patients to any drug dose is a reflection of the pharmacokinetic and pharmacodynamic properties of the drug and the specific patient. In this paper, we use pharmacokinetic and pharmacodynamic modeling to find an optimal drug dosing control policy to drive the patient to a desired MRSS score.