Anesthesia
Conditions
Keywords
Dexmedetomidine, Remifentanil, Pharmacodynamics, Interaction
Brief summary
The objective is to map the pharmacokinetic / pharmacodynamic interaction between dexmedetomidine and remifentanil by observing changes in anesthetic depth. These changes will be related to drug concentrations using pharmacokinetic/pharmacodynamic (PKPD) modeling.
Detailed description
This study is designed to investigate whether the use of a combination of dexmedetomidine and remifentanil is clinically useful to provide anesthesia during surgical and diagnostic procedures and whether it could be used for anesthetic induction. Furthermore the aim is to gain better insights in the required dosing regimens, the inter-individual variability in response towards the combination and the associated side effects. Better characterization of this drug-drug interaction will presumably lead to more precise dosing regimens, which in turn, will lead to a reduction in the occurrence of oversedation, side effects and recovery times. The objective is to map the pharmacokinetic / pharmacodynamic interaction between dexmedetomidine and remifentanil by observing changes in anesthetic depth, measured by hypnotic and analgesic endpoints such as modified observer's assessment of alertness and sedation scale (MOAA/S), response to electrical stimuli, response to laryngoscopy and electroencephalogram (EEG) derived indices. These effects will be related to drug concentrations using pharmacokinetic/pharmacodynamic (PKPD) modeling.
Interventions
DRUGDexmedetomidine
Single drug administration
DRUGRemifentanil
Single drug administration
Sponsors
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
All volunteers will receive 2 standardized anesthesia sessions with a washout period of at least one week between sessions. During the first session volunteers will receive dexmedetomidine, during the second session they will first receive remifentanil and afterwards the combination of drugs will be administered. Anesthetic depth will be evaluated by MOAA/S scores (see table 2), testing of tolerance to electrical stimuli and laryngoscopy. Furthermore multichannel EEG-data will be collected to get insight in the drug dependent characteristics. Measured effects will be related to drug plasma concentrations.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* American Society of Anesthesiologists (ASA) Physical Status 1 * No medical history of significance * No chronic use of medication, drugs, tobacco or more than 20 gr alcohol daily (oral contraceptives excluded). * Concerning the cognitive function: Volunteers are considered to have sufficient cognitive reserve if they are able to read and comprehend the patient information form, if they can adequately answer the anamnestic questions during the screening process and if they are allowed to provide legitimate written informed consent. * No selection will be made regarding ethnic background * No exclusion criterium is present
Exclusion criteria
* Known intolerance to dexmedetomidine or remifentanil * Volunteer refusal * Age \< 18 years or \>70 years * Pregnancy, or currently nursing * Hairstyle with dreadlocks (EEG-monitoring will not be possible) * Body mass index (BMI) \<18 or \>30 kg/m2. * Neurological disorder (epilepsy, the presence of a brain tumor, a history of brain surgery, hydrocephalic disorders, depression needing treatment with anti-depressive drugs, a history of brain trauma, a subarachnoidal bleeding, TIA or cerebral infarct, psychosis or dementia , schizophrenia, alcohol or drug abuse). * Diseases involving the cardiovascular system (hypertension, coronary artery disease, prior acute myocardial infarction, any valvular and/or myocardial disease involving
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance of Laryngoscopy (TOL) | 35 - 255 minutes | Tolerance of a laryngoscopy (yes/no) will be tested at the end of each infusion step during both studydays, when MOAA/s is 0 / 1 and will be related to the drug concentration(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified observer's assessment of alertness and sedation scale (MOAA/s) | During anesthesia sessions day 1 and day 2 | An hypnotic endpoint measuring depth of anesthesia. |
| Electrical stimulus | During anesthesia sessions day 1 and day 2 | Measuring analgesia by observing response to a standardized electrical stimulus |
| Electroencephalogram (EEG) | During anesthesia sessions day 1 and day 2 | A multichannel electroencephalogram will be recorded |
Countries
Netherlands
Outcome results
None listed