Remifentanil Effect-site Prediction by Algometry

Vall d'Hebron University Hospital (HUVH)

Status: Completed

Conditions: Conscious Sedation Failure During Procedure

Treatments: Drug: Remifentanil 1 MG Injection [Ultiva]; Device: Algometry; Drug: Midazolam 1 MG/ML Prefilled Syringe; Drug: Saline solution

Study type: Observational

Funder types: Other

Identifiers

NCT05115578

EPA (AG) 33/2017 (5097)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: Female

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

100 participants in 3 patient groups

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

Description:

Group I of 35 patients received a constant TCI effect-site target infusion of 1.5 ng/ml of remifentanil for 25 min.

Treatment:

Device: Algometry

Drug: Remifentanil 1 MG Injection [Ultiva]

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

Description:

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

Treatment:

Drug: Midazolam 1 MG/ML Prefilled Syringe

Device: Algometry

Drug: Remifentanil 1 MG Injection [Ultiva]

Group III Control

Description:

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

Treatment:

Drug: Saline solution

Device: Algometry