Development of a Pharmacokinetic/Pharmacodynamic Model of Dexmedetomidine, and the Effect of Repeated Auditory Stimulation on Pharmacodynamics of Dexmedetomidine.

Dexmedetomidine is an α2-adrenoceptor agonist that has only recently been registered for human use in Europe. It has sedative, analgesic and anxiolytic properties, but patients remain arousable. This makes it an ideal drug for procedures which require the patient to perform tasks, or for light sedation during procedures or in the Intensive Care Unit. Pharmacokinetic models of (anaesthetic) drugs can be used in target controlled infusions (TCI), to deliver stable plasma concentrations of drug during anaesthesia or sedation. There are several models available for dexmedetomidine at this time, but the most often used models (Dyck and Talke) underpredict the plasma concentration at higher concentrations. Also, plasma concentrations aren't what the clinician is interested in, but in the effect. Therefore, pharmacokinetic/pharmacodynamic (PKPD) models can be developed to titrate the drug to effect instead of plasma concentration, using TCI. This has been done for many anaesthetic drugs, but not for dexmedetomidine. Additionally, we want to investigate the effect of stimulation on the pharmacodynamic effect of dexmedetomidine. The reason for this is that patients under dexmedetomidine sedation are arousable by noises or touch. An operating room or ICU is never quiet, and there are always sounds of monitors, alarms, and talking between team members or activity around another patient in the same room, therefore the stimulation of the patient in such an environment may have a profound effect on the sedative effect of dexmedetomidine.