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

Universidad del Desarrollo

Status and phase: Enrolling; Phase 4

Conditions: Healthy; Surgery

Treatments: Drug: fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)

Study type: Interventional

Funder types: Other

Identifiers

NCT06417645

CEC-SSLR ord: 459

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

BIS predicted vs real

Experimental group

Description:

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.

Treatment:

Drug: fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)