Clinical trial NCT06417645: Re-evaluation of the Effect Site Model of the PKPD Propofol Eleveld Model
Official title: the BIS Index Response is Poorly Described by Propofol Effect Site Eleveld's Model After Applying a Perturbation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Healthy
Surgery
Keywords: propofol, Eleveld, BIS, predicted effect site model, non-lineal behavior
Lead sponsor: Universidad del Desarrollo
Sponsor class: OTHER
Collaborators: name: Technical University of Munich
First posted: 2024-05-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: healthy patients proposed for elective surgery longer than 60 min, received a standard protocol TCI iv anesthesia with EEG BIS index monitoring
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: predicted BIS index vs real BIS index
timeFrame: anesthesia
Secondary outcomes:
measure: evaluation of the evolution of the EEG frequency bands
timeFrame: anesthesia
Other outcomes:
Locations:
city: Osorno
country: Chile
facility: Hospital Base san José de Osorno
Study officials:
References:
citation: 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.
citation: 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.