Clinical trial NCT01879865: Dexmedetomidine PKPD Modeling and the Influence of Auditory Stimulation on Dexmedetomidine Effect
Official title: Development of a Pharmacokinetic/Pharmacodynamic Model of Dexmedetomidine, and the Effect of Repeated Auditory Stimulation on Pharmacodynamics of Dexmedetomidine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia
Sedation
Keywords: PKPD
Dexmedetomidine
Auditory Stimulation
Cardiac Output
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2013-06-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic/pharmacodynamic (PKPD) model
timeFrame: 190 minutes infusion (maximum); 5 hours recovery
Secondary outcomes:
measure: Effect of auditory stimulation on EEG-monitoring.
timeFrame: 190 minutes infusion (maximum); recovery 5 hours (maximum)
Other outcomes:
measure: Effect of dexmedetomidine on cardiac output
timeFrame: 190 minutes infusion (maximum), 5 hours recovery (maximum)
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University of Groningen
name: Michel MRF Struys, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, Struys MMRF. Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile. Br J Anaesth. 2017 Aug 1;119(2):211-220. doi: 10.1093/bja/aex086.
citation: Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, Struys MMRF. Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation. Br J Anaesth. 2017 Aug 1;119(2):200-210. doi: 10.1093/bja/aex085.