Re-evaluation of the Effect Site Model of the PKPD Propofol Eleveld Model (Eleved PD)

the BIS Index Response is Poorly Described by Propofol Effect Site Eleveld's Model After Applying a Perturbation

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Chile
  • Osorno, Chile
    • Recruiting
    • Hospital Base san José de Osorno
    • Contact: Pablo O Sepulveda, Dr. Med; Phone Number: 056994793336; Email: pasevou@gmail.com
    • Contact: Ignacio Barra, Dr. Med; Phone Number: 056951883419; Email: ignaciobarrac@icloud.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BIS predicted vs real; 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.

Drug: fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio); after a slow induction with propofol to loss of consiousness (LOC), we proceed to give remifentanil TCI and rocuronium and intubate the patient. After 5 min we infuse 15 mg/kg/h until 1%BSR observe in the BIS monitor. Then we reduce the TCI LOC predicted concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predicted BIS index vs real BIS index	we compare the BIS predicted from the Eleveld model vs the response of our patients uring all the anesthesia procedure	anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of the evolution of the EEG frequency bands	Evaluate the differents EEG frequency bands at LOC, at maximal perturbation and when we reach again the LOC predicted concentration	anesthesia

Collaborators and Investigators

• Sponsor: Universidad del Desarrollo
• Collaborators: Technical University of Munich

Publications and helpful links

General Publications

• Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12. Erratum In: Br J Anaesth. 2018 Aug;121(2):519.
• Sepulveda PO, Mora X. [Reevaluation of the time course of the effect of propofol described with the Schnider pharmacokinetic model]. Rev Esp Anestesiol Reanim. 2012 Dec;59(10):542-8. doi: 10.1016/j.redar.2012.07.019. Epub 2012 Oct 4. Spanish.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): September 15, 2023
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: May 11, 2024
• First Submitted That Met QC Criteria: May 11, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 11, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: propofol, Eleveld, BIS, predicted effect site model, non-lineal behavior
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: CEC-SSLR ord: 459

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No