Remifentanil Pharmacodynamics During Conscious Sedation From the Algometry Perspective. An Essential Standpoint to be Considered in Opioids Time-course Modelling Validation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Pressure pain threshold (PPT) 5 minutes
研究概览
简要总结
This study validates the pharmacodynamic analgesic predictions (effect) given by Minto's remifentanil pharmacokinetic and dynamic model in conscious sedation. This standard model is based on the electroencephalogram (EEG) changes induced by this opioid as a proxy for describing the remifentanil analgesic effect, which might be only valid for high concentrations. Validation of the standard remifentanil model for low concentrations under sedation is needed for safer remifentanil administration.
详细描述
According to pharmacokinetic and-dynamic (PK/PD) models, the proper use of anesthetics depends on the effect-sites mechanisms and the time-courses of action. This aspect is crucial for the practitioners to target the desired effect-site concentrations of the drugs (drug concentration at brain) by optimizing the drug administration using target control infusion (TCI) systems operating under these model predictions.
For more than two decades, the pharmacodynamic properties of remifentanil relied on Minto's model, which is based on processed EEG as the reference to quantify the analgesic effect and effect-site concentration estimate. This remifentanil pharmacodynamic was modeled under conditions administered to volunteers rapidly and at very high doses to induce substantial changes in the spontaneous processed EEG. The experimental concentrations and infusion rates are far from sedative levels, where the EEG has shown a clear response to hypnosis but not to analgesia or nociception.
Under the hypothesis that pharmacological models should predict equally well the effects induced by drugs at different concentrations levels, the purpose of this study is to evaluate and validate the pharmacodynamic predictions given by Minto's model in patients under conscious sedation using the algometry as a reference of nociception.
The study recruits 100 female patients scheduled for benign gynecological surgery divided into three groups. A group of 35 patients receives a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min. The second group of 35 follow the same protocol with a bolus of 1 mg of midazolam before the remifentanil infusion. The rest configures the control group under saline solution.
Experimental data consist of basal algometry (pressure pain threshold) aside from BIS index, blood pressure, and heart rate values and at time-points of 1.5, 5, 10, 15, 18, 20, and 25 minutes after induction.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Female patients scheduled for benign gynaecological surgery
- •18-80 years old
- •ASA I-III
排除标准
- •Morbid obesity
- •Conduct disorder or anxiety-depressive syndrome
- •Chronic treatment with psychotropic drugs or opiates
- •Pregnancy
- •Alcohol abuse
- •Documented allergy to remifentanil or midazolam
- •Refusal to participate in the study
研究组 & 干预措施
Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil
Group I of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min.
干预措施: Remifentanil 1 MG Injection [Ultiva] (Drug)
Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil
Group I of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min.
干预措施: Algometry (Device)
Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv
Group II of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min with a bolus of 1 mg of midazolam previous to the remifentanil infusion
干预措施: Remifentanil 1 MG Injection [Ultiva] (Drug)
Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv
Group II of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min with a bolus of 1 mg of midazolam previous to the remifentanil infusion
干预措施: Midazolam 1 MG/ML Prefilled Syringe (Drug)
Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv
Group II of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min with a bolus of 1 mg of midazolam previous to the remifentanil infusion
干预措施: Algometry (Device)
Group III Control
Group III of 30 patients. The same TCI system provided the saline solution in the control group under an equivalent simulation profile to the remifentanil administration
干预措施: Saline solution (Drug)
Group III Control
Group III of 30 patients. The same TCI system provided the saline solution in the control group under an equivalent simulation profile to the remifentanil administration
干预措施: Algometry (Device)
结局指标
主要结局
Pressure pain threshold (PPT) 5 minutes
时间窗: 5 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 5 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) Baseline
时间窗: Baseline
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry before starting the administration of remifentanil.
Pressure pain threshold (PPT) 1.5 minutes
时间窗: 1.5 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 1.5 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) 10 minutes
时间窗: 10 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 10 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) 15 minutes
时间窗: 15 minutes
Measurement of pressure pain threshold(0 - 1.000 kPa) by algometry 15 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) 18 minutes
时间窗: 18 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 18 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) 20 minutes
时间窗: 20 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 20 minutes after starting the administration of remifentanil.
Pressure pain threshold (PPT) 25 minutes
时间窗: 25 minutes
Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 25 minutes after starting the administration of remifentanil.
Infusion rate
时间窗: Continous measurements every 1 second for the whole experiment of 25 minutes
Remifentanil infusion rate (ml/h) administered during the experiment to the patient provided by the TCI system.
Remifentanil Plasma Concentration (Cp)
时间窗: Continous measurements every 1 second for the whole experiment of 25 minutes
Patient's remifentanil plasma concentration (ng/ml) evolution during the experiment given by Minto's model implemented in the TCI system.
Remifentanil Effect Concentration (Ce)
时间窗: Continous measurements every 1 second for the whole experiment of 25 minutes
Patient's remifentanil effect concentration (ng/ml) evolution during the experiment given by Minto's model implemented in the TCI system.
次要结局
- Age(Single annotation.)
- Mean arterial pressure (MAP) Baseline(Baseline)
- Mean arterial pressure (MAP) 1.5 min(1.5 minutes)
- Mean arterial pressure (MAP) 5 min(5 minutes)
- Mean arterial pressure (MAP) 10 min(10 minutes)
- Mean arterial pressure (MAP) 15 min(15 minutes)
- Mean arterial pressure (MAP) 18 min(18 minutes)
- Mean arterial pressure (MAP) 20 min(20 minutes)
- Mean arterial pressure (MAP) 25 min(25 minutes)
- Heart Rate (HR) Baseline(Baseline)
- Heart Rate (HR) 1.5 min(1.5 minutes)
- Heart Rate (HR) 5 min(5 minutes)
- Heart Rate (HR) 10 min(10 minutes)
- Heart Rate (HR) 15 min(15 minutes)
- Heart Rate (HR) 18 min(18 minutes)
- Heart Rate (HR) 20 min(20 minutes)
- Bispectrum (BIS) Baseline(Baseline)
- Bispectrum (BIS) 1.5 minutes(1.5 minutes)
- Bispectrum (BIS) 5 minutes(5 minutes)
- Bispectrum (BIS) 10 minutes(10 minutes)
- Bispectrum (BIS) 15 minutes(15 minutes)
- Bispectrum (BIS) 20 minutes(20 minutes)
- Bispectrum (BIS) 25 minutes(25 minutes)