Remifentanil Effect-site Prediction by Algometry
- Conditions
- Conscious Sedation Failure During Procedure
- Interventions
- Drug: Saline solutionDevice: Algometry
- Registration Number
- NCT05115578
- Brief Summary
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.
- Detailed Description
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.
Minto's remifentanil pharmacodynamic model validation relies on comparing the levels and temporal evolution of the algometry measurements during the whole experiment concerning the effect-site estimations provided by the TCI-pump Minto's model.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 100
- Female patients scheduled for benign gynaecological surgery
- 18-80 years old
- ASA I-III
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil Remifentanil 1 MG Injection [Ultiva] Group I of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min. Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil Algometry Group I of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min. Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv Remifentanil 1 MG Injection [Ultiva] 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 Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv Midazolam 1 MG/ML Prefilled Syringe 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 Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv Algometry 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 Group III Control Saline solution 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 Group III Control Algometry 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
- Primary Outcome Measures
Name Time Method Pressure pain threshold (PPT) 5 minutes 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 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 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 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 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 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 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 25 minutes Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 25 minutes after starting the administration of remifentanil.
Infusion rate 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) 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) 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.
- Secondary Outcome Measures
Name Time Method Age Single annotation. Apart from standard anthropometric data (Weight, Height, etc), age is of significant relevance for evaluating the possible effect of age on the pharmacodynamic properties of remifentanil and the algometry.
Mean arterial pressure (MAP) Baseline Baseline Baseline mean arterial pressure (mmHg) from standard hemodynamic monitor.
Mean arterial pressure (MAP) 1.5 min 1.5 minutes Measurement of mean arterial pressure (mmHg) 1.5 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 5 min 5 minutes Measurement of mean arterial pressure (mmHg) 5 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 10 min 10 minutes Measurement of mean arterial pressure (mmHg) 10 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 15 min 15 minutes Measurement of mean arterial pressure (mmHg) 15 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 18 min 18 minutes Measurement of mean arterial pressure (mmHg) 18 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 20 min 20 minutes Measurement of mean arterial pressure (mmHg) 20 minutes after starting the administration of remifentanil.
Mean arterial pressure (MAP) 25 min 25 minutes Measurement of mean arterial pressure (mmHg) 25 minutes after starting the administration of remifentanil.
Heart Rate (HR) Baseline Baseline Baseline measurement of heart rate (beats/min)
Heart Rate (HR) 1.5 min 1.5 minutes Measurement of heart rate (beats/min) 1.5 minutes after starting the administration of remifentanil.
Heart Rate (HR) 5 min 5 minutes Measurement of heart rate (beats/min) 5 minutes after starting the administration of remifentanil.
Heart Rate (HR) 10 min 10 minutes Measurement of heart rate (beats/min) 10 minutes after starting the administration of remifentanil.
Heart Rate (HR) 15 min 15 minutes Measurement of heart rate (beats/min) 15 minutes after starting the administration of remifentanil.
Heart Rate (HR) 18 min 18 minutes Measurement of heart rate (beats/min) 18 minutes after starting the administration of remifentanil.
Heart Rate (HR) 20 min 20 minutes Measurement of heart rate (beats/min) 20 minutes after starting the administration of remifentanil.
Bispectrum (BIS) Baseline Baseline Baseline measurement of EEG Bispectral index (adimensional index from 0- to 100).
Bispectrum (BIS) 1.5 minutes 1.5 minutes EEG Bispectral index (adimensional index from 0- to 100) 1.5 minutes after starting the administration of remifentanil.
Bispectrum (BIS) 5 minutes 5 minutes EEG Bispectral index (adimensional index from 0- to 100) 5 minutes after starting the administration of remifentanil.
Bispectrum (BIS) 10 minutes 10 minutes EEG Bispectral index (adimensional index from 0- to 100) 10 minutes after starting the administration of remifentanil.
Bispectrum (BIS) 15 minutes 15 minutes EEG Bispectral index (adimensional index from 0- to 100) 15 minutes after starting the administration of remifentanil.
Bispectrum (BIS) 20 minutes 20 minutes EEG Bispectral index (adimensional index from 0- to 100) 20 minutes after starting the administration of remifentanil.
Bispectrum (BIS) 25 minutes 25 minutes EEG Bispectral index (adimensional index from 0- to 100) 25 minutes after starting the administration of remifentanil.
Trial Locations
- Locations (1)
Ana Abad-Torrent
🇪🇸Barcelona, Spain