Re-evaluation of the Effect Site Model of the PKPD Propofol Eleveld Model

Phase 4

Recruiting

• Conditions: Surgery; Healthy
• Interventions: Drug: fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)

• Registration Number: NCT06417645
• Lead Sponsor: Universidad del Desarrollo

Brief Summary

in healthy patients undergoing elective surgery, after a very slow induction, using Eleveld's kinetics as a reference, after loss of consciousness (LOC) and intubation, proceed to infuse propofol until 1% burst suppression ratio is obtained. Then return to the LOC concentration. The BISindex predicted by the model and the real one will be evaluated. The evolution of spectral density frequencies over time will also be evaluated.

Detailed Description

Eleveld is a recently developed PKPD model of propofol, which includes multiple covariates in its pharmacokinetics.

This model, called Universal, includes data from all studies conducted with plasma levels in the world, where the principal investigator (PSV) has been directly involved.

For pharmacodynamics (PD), Eleveld, includes processed electroencephalogram (EEG) readings, but only by nominal BIS index.

The use of BIS as a unique marker of propofol hypnosis shows multiple limitations as it results from a computer algorithmic application, which can be influenced by drugs, inter-individual variability, among others.

Therefore, to determine the effect there are nowadays more accurate tools such as spectrogram processing and determination of alpha power by spectral density (PDS).

This project aims to re-evaluate the modelling of the temporal behaviour of the effect in the BIS index, using the reference of the Eleveld kinetic model, associated to a spectrogram that allows the evaluation of the alpha and delta band dynamics as a predictor of the propofol effect.

In our study we intend to replace the BIS value by the alpha and delta power progress in decibels (dB) and eventually build a pharmacodynamic (PD) model with a marker more associated to the specific cortical electrical phenomenon.

Study Timeline

• Study Start: 2013-09-01
• Primary Completion: 2023-09-15
• Status Verified: 2024-05
• Study First Submitted: 2024-05-11
• Study First Submitted QC: 2024-05-11
• Last Update Submitted: 2024-05-11
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16
• Study Completion: 2024-09-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• ASA I-II patients between 18 and 60 years of age, who undergo elective surgery in the central ward of the Hospital Base San José Osorno, Chile. Consecutive patients from the beginning of the study up to 12 months from the admission of the first patient.

Exclusion Criteria

• Emergency surgery patient.
• Patients with dementia, delirium or altered state of consciousness.
• Full stomach or risk of aspiration.
• Allergic to propofol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIS predicted vs real	fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)	After slow propofol induction and standard monitoring with BIS EEG monitor. The propofol infusion guided by iTIVA simulator (Android / iOS) using Eleveld kinetic model. LOC (defined as loss of response to loud call and shoulder movement-touch), the same concentration of propofol will be maintained for 5 minutes to assess EEG stability. .Intubation will proceed as usual, starting remifentanil at 4.5 ng/ml and rocuronium bromide 0.6 mg/kg. After 5 min and before the start of surgery, propofol will be infused at 15 mg/kg/h until 1% BSR is reached, observed on the BIS monitor, and then return to the rate that represents the LOC concentration. EEG data shall be retrieved from the BIS monitor via USB. Post hoc using the software tivatrainer.com we will simulate the Eleved calculated plasma concentration and the Bis prediction with our BIS real data.

Primary Outcome Measures

Name	Time	Method
predicted BIS index vs real BIS index	anesthesia	we compare the BIS predicted from the Eleveld model vs the response of our patients uring all the anesthesia procedure

Secondary Outcome Measures

Name	Time	Method
evaluation of the evolution of the EEG frequency bands	anesthesia	Evaluate the differents EEG frequency bands at LOC, at maximal perturbation and when we reach again the LOC predicted concentration

Trial Locations

Locations (1)

Hospital Base san José de Osorno; 🇨🇱 Osorno, Chile