Dexmedetomidine PKPD Modeling and the Influence of Auditory Stimulation on Dexmedetomidine Effect

Study Overview
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Brief Summary
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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.

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

Conditions
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Anesthesia, Sedation

Intervention / Treatment
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* Other: Non-stimulation
* Other: Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) Physical Status 1 No medical history of significance No chronic use of medication, alcohol, drugs or tobacco (oral contraceptives excluded) Exclusion Criteria: Contraindications for use of dexmedetomidine Known intolerance to dexmedetomidine Body mass index (BMI) <18 or >30 kg/m2 Volunteer refusal Pregnancy, or currently nursing Bilateral non-patent ulnar artery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Non-stimulation<br>No auditory stimulation during dexmedetomidine infusion and recovery. | Other: Non-stimulation<br>* The volunteers will be wearing noise-cancelling headphones (silent) and will be stimulated as little as possible. The volunteer will be instructed to keep his/her eyes closed.<br>|
| Other: Stimulation<br>Auditory stimulation during dexmedetomidine infusion and recovery. | Other: Stimulation<br>* The volunteers will be wearing noise-cancelling headphones, through which they will hear a continuous loop of recorded operating room noise (monitor beeps, talking), to simulate operating room conditions. The volunteer will be instructed to keep his/her eyes closed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic/pharmacodynamic (PKPD) model | Development of a pharmacokinetic/pharmacodynamic model during dexmedetomidine infusion and recovery using plasma concentrations, EEG-monitoring and sedation scales as endpoints. | 190 minutes infusion (maximum); 5 hours recovery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of auditory stimulation on EEG-monitoring. |  | 190 minutes infusion (maximum); recovery 5 hours (maximum) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PKPD, Dexmedetomidine, Auditory Stimulation, Cardiac Output