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

Anesthesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01879865
• Other study ID #: Dex-PKPD/01
• Status: Completed
• Phase: N/A
• Start date: June 2013
• Est. completion date: November 2013

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 72 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia
• Sedation

Intervention

Other:
• Non-stimulation
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.
• Stimulation
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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect of dexmedetomidine on cardiac output		190 minutes infusion (maximum), 5 hours recovery (maximum)
Primary	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	Effect of auditory stimulation on EEG-monitoring.		190 minutes infusion (maximum); recovery 5 hours (maximum)