NCT05115578

Remifentanil Effect-site Prediction by Algometry

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 100 (actual)
• Sponsor: Hospital Universitari Vall d'Hebron Research Institute · Academic / Other
• Sex: Female
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

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.

Conditions

• Conscious Sedation Failure During Procedure

Interventions

Type	Name	Description
DRUG	Remifentanil 1 MG Injection [Ultiva]	Group I TCI effect-site target infusion of 1.5 ng/ml of remifentanil.
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
DRUG	Saline solution	Group III Control
DEVICE	Algometry	The algometry technique is used to assess the pain pressure threshold as an analgesic effect of remifentanil concerning Minto's model prediction.

Timeline

• Start date: 2017-03-01
• Primary completion: 2020-05-15
• Completion: 2020-09-30
• First posted: 2021-11-10
• Last updated: 2021-11-10

Locations

1 site across 1 country: Spain

Regulatory

• FDA-regulated drug study