Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06346158 |
| Other study ID # |
2024-3615 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2024 |
| Est. completion date |
May 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Ciusss de L'Est de l'Île de Montréal |
| Contact |
Louis Morisson, MD, MSc |
| Phone |
514-252-3400 |
| Email |
louis.morisson[@]umontreal.ca |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The goal of this observational study is to explore the variability of the concentration at
the effect site (Ce) of propofol to reach deep anesthesia (DA) during induction of general
anesthesia in adults.
The investigators hypothesized that there is a great variability in this Ce that could be
precisely explained by
- Electroencephalographic (EEG) features available prior to induction of anesthesia
- Cognitive performance
- Patients characteristics Participants will undergo preoperative cognitive testing and
awake EEG. Then, induction of general anesthesia will be performed using continuous
infusion of propofol. The Ce at which Deep anesthesia is observed will be recorded.
Description:
Propofol is the most widely used anesthetic to induce general anesthesia (GA). However, as
opposed to volatile anesthesia, propofol concentration monitoring is not directly available
in humans. Thus, the use of a pharmacokinetic/pharmacodynamic (PK/PD) model in
target-controlled infusion (TCI) is recommended. During infusion, the concentration at
effect-site (Ce) is assumed to correlate with the level of hypnosis. However, There is a
large variability in propofol requirements in common practice. The variability in propofol
requirements is attributed to demographic factors, genetic polymorphism, procedure-related
changes, and individual sensitivity. Previous studies have shown that EEG characteristics
change with age and cognitive status.
Hypothesis : There is a large interindividual variability in patients' sensitivity to
propofol which can be precisely modeled using clinical, demographic, and
electroencephalographic (EEG) features available prior to induction of general anesthesia.
The investigators also hypothesise that this sensitivity to propofol may identify vulnerable
brain phenotype related to poor cognitive performance.
Specific objectives: Primary: to investigate the variability of Ce propofol at which deep
anesthesia (DA) occurs during induction of general anesthesia (CeDA). Secondary: to explore
the relationship between demographics, cognitive performance, and EEG variables with the
independent CeDA variable. Tertiary: to develop and validate a machine learning algorithm to
predict CeDA based on clinical, demographic and EEG features obtained prior the induction of
general anesthesia.
Methods: This prospective monocentric observational study will include 110 participants of 18
years of age or older scheduled for surgery under general anesthesia. Baseline cognitive
performance will be assessed using the Montreal Cognitive Assessment. Induction of GA will be
performed using 300ml.h-1 of 1% propofol until DA (Defined as a Patient State Index (PSI) <
30) is observed. The primary endpoint will be the Ce propofol at which deep anesthesia (CeDA)
occurs as calculated by the Eleveld PK/PD model for propofol. Preoperative raw EEG waveforms
from the SedLine monitor will be used to extract statistical, entropic, and spectral
features. High-density EEG (128 channels) will also be recorded in a subsample of 40 patients
to extract brain functional connectivity features. These features will be entered in a
generalized additive model to predict CeDA. We will also develop and validate a machine
learning algorithm to predict CeDA based on these features.
Significance/Importance: The results of this study could provide a better understanding of
the determinants of the inter-individual variability observed in the pharmacodynamic effect
of anesthetic agents. Moreover, the prediction of CeDA may help clinicians in setting the
right and safe target in target-controlled infusion of propofol during induction of general
anesthesia and further limit the occurrence of deep anesthesia during surgery. Finally, the
knowledge of the link between EEG characteristics, sensitivity to anesthetics and cognitive
performance may lead to more personalized anesthesia delivery.
