Our 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…
ID
Source
Brief title
Condition
- Other condition
- Nervous system, skull and spine therapeutic procedures
Synonym
Health condition
gezonde vrijwiligers welk onder anesthesie worden gebracht
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary objective is to observe changes in anesthetic depth measured by
hypnotic and analgesic endpoints (MOAA/S, response to laryngoscopy and
electroencephalogram (EEG) derived indices, during administration of
dexmedetomidine or remifentanil and their combination, and to relate these
effects to drug concentrations using PKPD modeling (see ch.8 for details).
Secondary outcome
- To improve existing EEG-indices by gaining full EEG-recordings and relate
these to the anesthetic effects.
- To validate two previously developed TCI models (a dexmedetomidine model and
a remifentanil model, see references in our protocol)
- To relate ventilatory changes induced by each of the agents and by the
combination of both drugs, to the measured drug plasma concentrations.
- To relate hemodynamic changes induced by each of the agents and by the
combination of both drugs, to the measured drug plasma concentrations.
Background summary
Dexmedetomidine (DMED) is an *2-adrenoceptor agonist which is used as a
sedative in intensive care units and during surgical or diagnostic procedures.
It has sedative, analgesic and anxiolytic properties and only minimally affects
respiration. Studies investigating the analgesic properties of dexmedetomidine
found that exposure resulting in mild to deep sedation seems to lack analgesic
efficacy. This study is designed to investigate the interaction of
dexmedetomidine with the potent analgesic remifentanil (REMI). Remifentanil is
a strong analgesic, but lacks sedative potency. As such, these drugs might
prove an interesting combination.
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 we aim to gain better insights in the
required dosing regimens, the inter-individual variability in response towards
the combination and the associated side effects. We are convinced that a better
characterization of this drug-drug interaction will lead to more precise dosing
regimens, which in turn, will lead to a reduction in the occurrence of
oversedation, side effects and recovery times.
Study objective
Our 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 laryngoscopy
and electroencephalogram (EEG) derived indices. These effects will be related
to drug concentrations using pharmacokinetic/pharmacodynamic (PKPD) modeling.
Study design
Pharmacokinetic/pharmacodynamic modelling of a drug-drug interaction.
Intervention
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)
and testing of tolerance to 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.
Study burden and risks
Dexmedetomidine and remifentanil are both frequently used drugs in clinical
practice. They are safe to use in controlled settings, such as an operating
room or intensive care unit. The targets for dexmedetomidine used in this study
will be higher than the package insert indicates, but our cessation criteria
will prevent individuals from reaching dangerously high concentrations. Other
studies using similar criteria have had individuals reaching target
concentrations of up 14-16 ng/ml. Our maximum target concentration will be 8
ng/ml. An intravenous line (drug and fluid infusion) and an arterial line (for
blood sampling and blood pressure/cardiac output monitoring) will be inserted
before starting the study. Possible risks include hematoma, infiltration,
embolism and phlebitis, but these risks are considered rare, especially in
healthy volunteers. All other monitoring will be non-invasive.
hanzeplein 1
groningen 9713 EZ
NL
hanzeplein 1
groningen 9713 EZ
NL
Listed location countries
Age
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 decrease in ejection fraction, arrhythmias, which are either symptomatic or require continuous medication/pacemaker/automatic internal cardioverter defibrillator)
- Recent use of psycho-active medication (benzodiazepines, anti-epileptic drugs, parkinson medication, anti-depressant drugs, opioids) or more than 20 g of alcohol daily.
- Bilateral non-patent a. ulnaris
- Any other condition relevant to the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000945-37-NL |
| Other | na |
| CCMO | NL61190.056.17 |