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


Correspondence to: Wassim M. Haddad, School of Aerospace Engineering, Georgia Institute of Technology, Atlanta, GA, 30332-0150, USA.

E-mail: wm.haddad@aerospace.gatech.edu


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, the Richmond agitation–sedation scale, and the modified Ramsay sedation scale. 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 modified Ramsay sedation scale score. Copyright © 2012 John Wiley & Sons, Ltd.