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NCT Number: NCT05115578

Remifentanil Effect-site Prediction by Algometry

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.

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Key information

Conditions

Conscious Sedation Failure During Procedure

Age range

18 year–80 year

Sex eligibility

Female

Study type

Observational

Primary location

Ana Abad-Torrent

Barcelona, 08035, Spain

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Remifentanil 1 MG Injection [Ultiva]

Drug

Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil.

Other names: Opioid

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

Other names: Benzodiazepine

Saline Solution

Drug

Group III Control

Other names: 0.9% Sodium Chloride Injection

Algometry

Device

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

Primary outcomes

  1. Pressure pain threshold (PPT) Baseline

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 25 minutes

    Measurement of pressure pain threshold (0 - 1.000 kPa) by algometry 25 minutes after starting the administration of remifentanil.

  9. Infusion rate

    Time frame: 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)

    Time frame: 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)

    Time frame: 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 outcomes

  1. Age

    Time frame: 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

    Time frame: Baseline

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

  3. Mean arterial pressure (MAP) 1.5 min

    Time frame: 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

    Time frame: 5 minutes

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

  5. Mean arterial pressure (MAP) 10 min

    Time frame: 10 minutes

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

  6. Mean arterial pressure (MAP) 15 min

    Time frame: 15 minutes

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

  7. Mean arterial pressure (MAP) 18 min

    Time frame: 18 minutes

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

  8. Mean arterial pressure (MAP) 20 min

    Time frame: 20 minutes

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

  9. Mean arterial pressure (MAP) 25 min

    Time frame: 25 minutes

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

  10. Heart Rate (HR) Baseline

    Time frame: Baseline

    Baseline measurement of heart rate (beats/min)

  11. Heart Rate (HR) 1.5 min

    Time frame: 1.5 minutes

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

  12. Heart Rate (HR) 5 min

    Time frame: 5 minutes

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

  13. Heart Rate (HR) 10 min

    Time frame: 10 minutes

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

  14. Heart Rate (HR) 15 min

    Time frame: 15 minutes

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

  15. Heart Rate (HR) 18 min

    Time frame: 18 minutes

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

  16. Heart Rate (HR) 20 min

    Time frame: 20 minutes

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

  17. Bispectrum (BIS) Baseline

    Time frame: Baseline

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

  18. Bispectrum (BIS) 1.5 minutes

    Time frame: 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

    Time frame: 5 minutes

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

  20. Bispectrum (BIS) 10 minutes

    Time frame: 10 minutes

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

  21. Bispectrum (BIS) 15 minutes

    Time frame: 15 minutes

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

  22. Bispectrum (BIS) 20 minutes

    Time frame: 20 minutes

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

  23. Bispectrum (BIS) 25 minutes

    Time frame: 25 minutes

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

Sponsors and collaborators

Lead sponsor

Hospital Universitari Vall d'Hebron Research Institute

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Nov 10, 2021
Registry last updated
Nov 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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