Clinical trial NCT05115578: Remifentanil Effect-site Prediction by Algometry
Official title: Remifentanil Pharmacodynamics During Conscious Sedation From the Algometry Perspective. An Essential Standpoint to be Considered in Opioids Time-course Modelling Validation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Conscious Sedation Failure During Procedure
Keywords: Remifentanil
Algometry
Pharmacodynamics
TCI Infusion system
Conscious Sedation
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2021-11-10
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We enrolled 100 female patients scheduled for benign gynaecological surgery. A group of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min. The second group of 35 followed the same protocol with a bolus of 1 mg of midazolam previous to the remifentanil infusion to evaluate potential anxiolysis effects. The rest configured to the control group.

Algometry was used to quantify pressure pain thresholds regarding basal measurements at time-points of 1.5, 5, 10, 15, 18, 20, and 25 min after induction began beside the blood pressure and heart rate.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pressure pain threshold (PPT) Baseline
timeFrame: Baseline
measure: Pressure pain threshold (PPT) 1.5 minutes
timeFrame: 1.5 minutes
measure: Pressure pain threshold (PPT) 5 minutes
timeFrame: 5 minutes
measure: Pressure pain threshold (PPT) 10 minutes
timeFrame: 10 minutes
measure: Pressure pain threshold (PPT) 15 minutes
timeFrame: 15 minutes
measure: Pressure pain threshold (PPT) 18 minutes
timeFrame: 18 minutes
measure: Pressure pain threshold (PPT) 20 minutes
timeFrame: 20 minutes
measure: Pressure pain threshold (PPT) 25 minutes
timeFrame: 25 minutes
measure: Infusion rate
timeFrame: Continous measurements every 1 second for the whole experiment of 25 minutes
measure: Remifentanil Plasma Concentration (Cp)
timeFrame: Continous measurements every 1 second for the whole experiment of 25 minutes
measure: Remifentanil Effect Concentration (Ce)
timeFrame: Continous measurements every 1 second for the whole experiment of 25 minutes
Secondary outcomes:
measure: Age
timeFrame: Single annotation.
measure: Mean arterial pressure (MAP) Baseline
timeFrame: Baseline
measure: Mean arterial pressure (MAP) 1.5 min
timeFrame: 1.5 minutes
measure: Mean arterial pressure (MAP) 5 min
timeFrame: 5 minutes
measure: Mean arterial pressure (MAP) 10 min
timeFrame: 10 minutes
measure: Mean arterial pressure (MAP) 15 min
timeFrame: 15 minutes
measure: Mean arterial pressure (MAP) 18 min
timeFrame: 18 minutes
measure: Mean arterial pressure (MAP) 20 min
timeFrame: 20 minutes
measure: Mean arterial pressure (MAP) 25 min
timeFrame: 25 minutes
measure: Heart Rate (HR) Baseline
timeFrame: Baseline
measure: Heart Rate (HR) 1.5 min
timeFrame: 1.5 minutes
measure: Heart Rate (HR) 5 min
timeFrame: 5 minutes
measure: Heart Rate (HR) 10 min
timeFrame: 10 minutes
measure: Heart Rate (HR) 15 min
timeFrame: 15 minutes
measure: Heart Rate (HR) 18 min
timeFrame: 18 minutes
measure: Heart Rate (HR) 20 min
timeFrame: 20 minutes
measure: Bispectrum (BIS) Baseline
timeFrame: Baseline
measure: Bispectrum (BIS) 1.5 minutes
timeFrame: 1.5 minutes
measure: Bispectrum (BIS) 5 minutes
timeFrame: 5 minutes
measure: Bispectrum (BIS) 10 minutes
timeFrame: 10 minutes
measure: Bispectrum (BIS) 15 minutes
timeFrame: 15 minutes
measure: Bispectrum (BIS) 20 minutes
timeFrame: 20 minutes
measure: Bispectrum (BIS) 25 minutes
timeFrame: 25 minutes
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Ana Abad-Torrent
Study officials:
affiliation: University Vall d'Hebron Hospital
name: Ana Abad-Torrent, M.D
role: PRINCIPAL_INVESTIGATOR
References: