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

NCT01879865 | Completed

• 1 other identifier: Dex-PKPD/01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Anesthesia; Sedation

Keywords

PKPD; Dexmedetomidine; Auditory Stimulation; Cardiac Output

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Effect of auditory stimulation on EEG-monitoring.

  190 minutes infusion (maximum); recovery 5 hours (maximum)

Other Outcomes (1)

• Effect of dexmedetomidine on cardiac output

  190 minutes infusion (maximum), 5 hours recovery (maximum)

Study Arms (2)

Non-stimulation

OTHER

No auditory stimulation during dexmedetomidine infusion and recovery.

Other: Non-stimulation

Stimulation

OTHER

Auditory stimulation during dexmedetomidine infusion and recovery.

Other: Stimulation

Interventions

Non-stimulation OTHER

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.

Non-stimulation

Stimulation OTHER

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.

Stimulation

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713EZ, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 28854543 DERIVED

• 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.

  PMID: 28854538 DERIVED

Study Officials

• Michel MRF Struys, MD, PhD

  University of Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: June 18, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

NL (1)