Pharmacodynamic Interaction of REMI and DMED (PIRAD)

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 4

Conditions: Anesthesia

Treatments: Drug: Dexmedetomidine; Drug: Remifentanil

Study type: Interventional

Funder types: Other

Identifiers

NCT03143972

PIRAD-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Dexmedetomidine only

Experimental group

Description:

Dexmedetomidine will be administered by effect-site TCI according to the Hannivoort model extended with an effect-site rate constant of 0.0428min-1. A stepwise increasing dosing regimen will be given, with concentrations targeting an effect site concentration of 1 ng/ml (40 min), 3 ng/ml (50 min), 4 ng/ml (40 min), 5 ng/ml (40 min) and 8 ng/ml (70 min).

Treatment:

Drug: Dexmedetomidine

Remifentanil only

Experimental group

Description:

Remifentanil will be administered by effect-site TCI according to the Eleveld model. A stepwise increasing dosing regimen will be given, with concentrations targeting an effect site concentration of 1 ng/ml (12 min), 2 ng/ml (12 min), 3 ng/ml (12 min), 5 ng/ml (12 min) and 7 ng/ml (12 min).

Treatment:

Drug: Remifentanil

Dexmedetomidine-Remifentanil interaction

Experimental group

Description:

A fixed background dose of dexmedetomidine will be given, this will be calculated after the first 5 subjects completed the dexmedetomidine only session. It will be set to 50% of the observed mean EC50TOL (Tolerance of Laryngoscopy). Remifentanil infusion will be administered by effect site TCI with stepwise increasing targets of 0.5 - 1.0 - 1.5 - 2.0 - 2.5 - 3.0 - 4.0 ng/ml, each lasting for 15 minutes.

Treatment:

Drug: Remifentanil

Drug: Dexmedetomidine