Pharmacodynamic Interactions Between Remifentanil and Dexmedetomidine (PIRAD)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Tolerance of Laryngoscopy (TOL)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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/m
- •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
研究组 & 干预措施
Dexmedetomidine only
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).
干预措施: Dexmedetomidine (Drug)
Remifentanil only
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).
干预措施: Remifentanil (Drug)
Dexmedetomidine-Remifentanil interaction
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.
干预措施: Dexmedetomidine (Drug)
Dexmedetomidine-Remifentanil interaction
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.
干预措施: Remifentanil (Drug)
结局指标
主要结局
Tolerance of Laryngoscopy (TOL)
时间窗: 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).
次要结局
- Electroencephalogram (EEG)(During anesthesia sessions day 1 and day 2)
- Modified observer's assessment of alertness and sedation scale (MOAA/s)(During anesthesia sessions day 1 and day 2)
- Electrical stimulus(During anesthesia sessions day 1 and day 2)