Remifentanil Effect-site Prediction by Algometry

Conscious Sedation Failure During Procedure Clinical Trial

Official title:

Remifentanil Pharmacodynamics During Conscious Sedation From the Algometry Perspective. An Essential Standpoint to be Considered in Opioids Time-course Modelling Validation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05115578
• Other study ID #: EPA (AG) 33/2017 (5097)
• Status: Completed
• Start date: March 1, 2017
• Est. completion date: September 30, 2020

Study information

• Verified date: October 2021
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 30, 2020
• Est. primary completion date: May 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Female patients scheduled for benign gynaecological surgery

• 18-80 years old

• ASA I-III

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Conscious Sedation Failure During Procedure

Intervention

Drug:
• Remifentanil 1 MG Injection [Ultiva]
Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil.
• Midazolam 1 MG/ML Prefilled Syringe
Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv
• Saline solution
Group III Control

Device:
• Algometry
The algometry technique is used to assess the pain pressure threshold as an analgesic effect of remifentanil concerning Minto's model prediction.

Locations

Country	Name	City	State
Spain	Ana Abad-Torrent	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pressure pain threshold (PPT) Baseline	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry before starting the administration of remifentanil.	Baseline
Primary	Pressure pain threshold (PPT) 1.5 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 1.5 minutes after starting the administration of remifentanil.	1.5 minutes
Primary	Pressure pain threshold (PPT) 5 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 5 minutes after starting the administration of remifentanil.	5 minutes
Primary	Pressure pain threshold (PPT) 10 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 10 minutes after starting the administration of remifentanil.	10 minutes
Primary	Pressure pain threshold (PPT) 15 minutes	Measurement of pressure pain threshold(0 - 1.000 kPa) by algometry 15 minutes after starting the administration of remifentanil.	15 minutes
Primary	Pressure pain threshold (PPT) 18 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 18 minutes after starting the administration of remifentanil.	18 minutes
Primary	Pressure pain threshold (PPT) 20 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 20 minutes after starting the administration of remifentanil.	20 minutes
Primary	Pressure pain threshold (PPT) 25 minutes	Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 25 minutes after starting the administration of remifentanil.	25 minutes
Primary	Infusion rate	Remifentanil infusion rate (ml/h) administered during the experiment to the patient provided by the TCI system.	Continous measurements every 1 second for the whole experiment of 25 minutes
Primary	Remifentanil Plasma Concentration (Cp)	Patient's remifentanil plasma concentration (ng/ml) evolution during the experiment given by Minto's model implemented in the TCI system.	Continous measurements every 1 second for the whole experiment of 25 minutes
Primary	Remifentanil Effect Concentration (Ce)	Patient's remifentanil effect concentration (ng/ml) evolution during the experiment given by Minto's model implemented in the TCI system.	Continous measurements every 1 second for the whole experiment of 25 minutes
Secondary	Age	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.	Single annotation.
Secondary	Mean arterial pressure (MAP) Baseline	Baseline mean arterial pressure (mmHg) from standard hemodynamic monitor.	Baseline
Secondary	Mean arterial pressure (MAP) 1.5 min	Measurement of mean arterial pressure (mmHg) 1.5 minutes after starting the administration of remifentanil.	1.5 minutes
Secondary	Mean arterial pressure (MAP) 5 min	Measurement of mean arterial pressure (mmHg) 5 minutes after starting the administration of remifentanil.	5 minutes
Secondary	Mean arterial pressure (MAP) 10 min	Measurement of mean arterial pressure (mmHg) 10 minutes after starting the administration of remifentanil.	10 minutes
Secondary	Mean arterial pressure (MAP) 15 min	Measurement of mean arterial pressure (mmHg) 15 minutes after starting the administration of remifentanil.	15 minutes
Secondary	Mean arterial pressure (MAP) 18 min	Measurement of mean arterial pressure (mmHg) 18 minutes after starting the administration of remifentanil.	18 minutes
Secondary	Mean arterial pressure (MAP) 20 min	Measurement of mean arterial pressure (mmHg) 20 minutes after starting the administration of remifentanil.	20 minutes
Secondary	Mean arterial pressure (MAP) 25 min	Measurement of mean arterial pressure (mmHg) 25 minutes after starting the administration of remifentanil.	25 minutes
Secondary	Heart Rate (HR) Baseline	Baseline measurement of heart rate (beats/min)	Baseline
Secondary	Heart Rate (HR) 1.5 min	Measurement of heart rate (beats/min) 1.5 minutes after starting the administration of remifentanil.	1.5 minutes
Secondary	Heart Rate (HR) 5 min	Measurement of heart rate (beats/min) 5 minutes after starting the administration of remifentanil.	5 minutes
Secondary	Heart Rate (HR) 10 min	Measurement of heart rate (beats/min) 10 minutes after starting the administration of remifentanil.	10 minutes
Secondary	Heart Rate (HR) 15 min	Measurement of heart rate (beats/min) 15 minutes after starting the administration of remifentanil.	15 minutes
Secondary	Heart Rate (HR) 18 min	Measurement of heart rate (beats/min) 18 minutes after starting the administration of remifentanil.	18 minutes
Secondary	Heart Rate (HR) 20 min	Measurement of heart rate (beats/min) 20 minutes after starting the administration of remifentanil.	20 minutes
Secondary	Bispectrum (BIS) Baseline	Baseline measurement of EEG Bispectral index (adimensional index from 0- to 100).	Baseline
Secondary	Bispectrum (BIS) 1.5 minutes	EEG Bispectral index (adimensional index from 0- to 100) 1.5 minutes after starting the administration of remifentanil.	1.5 minutes
Secondary	Bispectrum (BIS) 5 minutes	EEG Bispectral index (adimensional index from 0- to 100) 5 minutes after starting the administration of remifentanil.	5 minutes
Secondary	Bispectrum (BIS) 10 minutes	EEG Bispectral index (adimensional index from 0- to 100) 10 minutes after starting the administration of remifentanil.	10 minutes
Secondary	Bispectrum (BIS) 15 minutes	EEG Bispectral index (adimensional index from 0- to 100) 15 minutes after starting the administration of remifentanil.	15 minutes
Secondary	Bispectrum (BIS) 20 minutes	EEG Bispectral index (adimensional index from 0- to 100) 20 minutes after starting the administration of remifentanil.	20 minutes
Secondary	Bispectrum (BIS) 25 minutes	EEG Bispectral index (adimensional index from 0- to 100) 25 minutes after starting the administration of remifentanil.	25 minutes