Remifentanil Effect-site Prediction by Algometry

NCT ID: NCT05115578

Last Updated: 2021-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-01

Study Completion Date

2020-09-30

Brief Summary

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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

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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.

Conditions

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Conscious Sedation Failure During Procedure

Keywords

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Remifentanil Algometry Pharmacodynamics TCI Infusion system Conscious Sedation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Remifentanil 1 MG Injection [Ultiva]

Intervention Type DRUG

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

Algometry

Intervention Type DEVICE

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

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

Remifentanil 1 MG Injection [Ultiva]

Intervention Type DRUG

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

Midazolam 1 MG/ML Prefilled Syringe

Intervention Type DRUG

Group II TCI effect-site target infusion of 1.5 ng/ml of remifentanil + 1 mg Midazolam iv

Algometry

Intervention Type DEVICE

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

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

Saline solution

Intervention Type DRUG

Group III Control

Algometry

Intervention Type DEVICE

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

Interventions

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Remifentanil 1 MG Injection [Ultiva]

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

Intervention Type 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

Intervention Type DRUG

Saline solution

Group III Control

Intervention Type DRUG

Algometry

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

Intervention Type DEVICE

Other Intervention Names

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Opioid Benzodiazepine 0.9% Sodium Chloride Injection Somedic Type IIĀ®, Sweden

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ana Abad-Torrent, M.D

Role: PRINCIPAL_INVESTIGATOR

University Vall d'Hebron Hospital

Locations

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Ana Abad-Torrent

Barcelona, , Spain

Site Status

Countries

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Spain

Other Identifiers

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EPA (AG) 33/2017 (5097)

Identifier Type: -

Identifier Source: org_study_id