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Remifentanil Effect-site Prediction by Algometry

Sponsor
Hospital Universitari Vall d'Hebron Research Institute (Other)
Overall Status
Completed
CT.gov ID
NCT05115578
Collaborator
(none)
100
Enrollment
1
Location
43
Actual Duration (Months)
2.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Remifentanil 1 MG Injection [Ultiva]
  • Drug: Midazolam 1 MG/ML Prefilled Syringe
  • Drug: Saline solution
  • Device: Algometry

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.

Study Design

Study Type:
Observational
Actual Enrollment :
100 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Remifentanil Pharmacodynamics During Conscious Sedation From the Algometry Perspective. An Essential Standpoint to be Considered in Opioids Time-course Modelling Validation
Actual Study Start Date :
Mar 1, 2017
Actual Primary Completion Date :
May 15, 2020
Actual Study Completion Date :
Sep 30, 2020

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: Remifentanil 1 MG Injection [Ultiva]
Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil.
Other Names:
  • Opioid

    • Device: Algometry
    The algometry technique is used to assess the pain pressure threshold as an analgesic effect of remifentanil concerning Minto's model prediction.
    Other Names:
  • Somedic Type II®, Sweden

    		•
    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

    Drug: Remifentanil 1 MG Injection [Ultiva]
    Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil.
    Other Names:
  • Opioid

    • Drug: Midazolam 1 MG/ML Prefilled Syringe
    Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv
    Other Names:
  • Benzodiazepine

    • Device: Algometry
    The algometry technique is used to assess the pain pressure threshold as an analgesic effect of remifentanil concerning Minto's model prediction.
    Other Names:
  • Somedic Type II®, Sweden

    		•
    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

    Drug: Saline solution
    Group III Control
    Other Names:
  • 0.9% Sodium Chloride Injection

    • Device: Algometry
    The algometry technique is used to assess the pain pressure threshold as an analgesic effect of remifentanil concerning Minto's model prediction.
    Other Names:
  • Somedic Type II®, Sweden

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pressure pain threshold (PPT) Baseline [Baseline]

      Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry before starting the administration of remifentanil.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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

    1. 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.

    2. Mean arterial pressure (MAP) Baseline [Baseline]

      Baseline mean arterial pressure (mmHg) from standard hemodynamic monitor.

    3. 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.

    4. Mean arterial pressure (MAP) 5 min [5 minutes]

      Measurement of mean arterial pressure (mmHg) 5 minutes after starting the administration of remifentanil.

    5. Mean arterial pressure (MAP) 10 min [10 minutes]

      Measurement of mean arterial pressure (mmHg) 10 minutes after starting the administration of remifentanil.

    6. Mean arterial pressure (MAP) 15 min [15 minutes]

      Measurement of mean arterial pressure (mmHg) 15 minutes after starting the administration of remifentanil.

    7. Mean arterial pressure (MAP) 18 min [18 minutes]

      Measurement of mean arterial pressure (mmHg) 18 minutes after starting the administration of remifentanil.

    8. Mean arterial pressure (MAP) 20 min [20 minutes]

      Measurement of mean arterial pressure (mmHg) 20 minutes after starting the administration of remifentanil.

    9. Mean arterial pressure (MAP) 25 min [25 minutes]

      Measurement of mean arterial pressure (mmHg) 25 minutes after starting the administration of remifentanil.

    10. Heart Rate (HR) Baseline [Baseline]

      Baseline measurement of heart rate (beats/min)

    11. Heart Rate (HR) 1.5 min [1.5 minutes]

      Measurement of heart rate (beats/min) 1.5 minutes after starting the administration of remifentanil.

    12. Heart Rate (HR) 5 min [5 minutes]

      Measurement of heart rate (beats/min) 5 minutes after starting the administration of remifentanil.

    13. Heart Rate (HR) 10 min [10 minutes]

      Measurement of heart rate (beats/min) 10 minutes after starting the administration of remifentanil.

    14. Heart Rate (HR) 15 min [15 minutes]

      Measurement of heart rate (beats/min) 15 minutes after starting the administration of remifentanil.

    15. Heart Rate (HR) 18 min [18 minutes]

      Measurement of heart rate (beats/min) 18 minutes after starting the administration of remifentanil.

    16. Heart Rate (HR) 20 min [20 minutes]

      Measurement of heart rate (beats/min) 20 minutes after starting the administration of remifentanil.

    17. Bispectrum (BIS) Baseline [Baseline]

      Baseline measurement of EEG Bispectral index (adimensional index from 0- to 100).

    18. 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.

    19. Bispectrum (BIS) 5 minutes [5 minutes]

      EEG Bispectral index (adimensional index from 0- to 100) 5 minutes after starting the administration of remifentanil.

    20. Bispectrum (BIS) 10 minutes [10 minutes]

      EEG Bispectral index (adimensional index from 0- to 100) 10 minutes after starting the administration of remifentanil.

    21. Bispectrum (BIS) 15 minutes [15 minutes]

      EEG Bispectral index (adimensional index from 0- to 100) 15 minutes after starting the administration of remifentanil.

    22. Bispectrum (BIS) 20 minutes [20 minutes]

      EEG Bispectral index (adimensional index from 0- to 100) 20 minutes after starting the administration of remifentanil.

    23. Bispectrum (BIS) 25 minutes [25 minutes]

      EEG Bispectral index (adimensional index from 0- to 100) 25 minutes after starting the administration of remifentanil.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ana Abad-Torrent Barcelona Spain 08035

    Sponsors and Collaborators

    • Hospital Universitari Vall d'Hebron Research Institute

    Investigators

    • Principal Investigator: Ana Abad-Torrent, M.D, University Vall d'Hebron Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hospital Universitari Vall d'Hebron Research Institute
    ClinicalTrials.gov Identifier:
    NCT05115578
    Other Study ID Numbers:
    • EPA (AG) 33/2017 (5097)
    First Posted:
    Nov 10, 2021
    Last Update Posted:
    Nov 10, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hospital Universitari Vall d'Hebron Research Institute
    Remifentanil
    Algometry
    Pharmacodynamics
    TCI Infusion system
    Conscious Sedation
    Additional relevant MeSH terms:
    Midazolam
    Remifentanil

    Study Results

    No Results Posted as of Nov 10, 2021