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

Healthy Clinical Trial

— Eleved PD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06417645
• Other study ID #: CEC-SSLR ord: 459
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2013
• Est. completion date: September 15, 2024

Study information

• Verified date: May 2024
• Source: Universidad del Desarrollo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: September 15, 2024
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Surgery

Intervention

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.

Locations

Country	Name	City	State
Chile	Hospital Base san José de Osorno	Osorno

Sponsors (2)

Lead Sponsor	Collaborator
Universidad del Desarrollo	Technical University of Munich

Country where clinical trial is conducted

Chile, 

References & Publications (2)

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 A — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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