Effect of intravenous versus inhaled anesthetics on blood-brain barrier dysfunction and neuroinflammation in elderly patients undergoing major surgery: study protocol of a randomized controlled trial.
Humans
Blood-Brain Barrier
/ drug effects
Aged
Anesthetics, Inhalation
/ administration & dosage
Randomized Controlled Trials as Topic
Postoperative Cognitive Complications
/ prevention & control
Sevoflurane
/ administration & dosage
Neuroinflammatory Diseases
/ blood
Anesthetics, Intravenous
/ administration & dosage
Male
Female
Middle Aged
Propofol
/ administration & dosage
S100 Calcium Binding Protein beta Subunit
/ blood
Biomarkers
/ blood
Treatment Outcome
Inflammation Mediators
/ blood
Blood-brain barrier
Cerebrospinal fluid
Inhaled anesthetics
Intravenous anesthetics
Neuroinflammation
Postoperative cognitive dysfunction
Postoperative delirium
S100 calcium binding protein β (S100β)
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
16 Oct 2024
16 Oct 2024
Historique:
received:
19
06
2024
accepted:
27
09
2024
medline:
17
10
2024
pubmed:
17
10
2024
entrez:
16
10
2024
Statut:
epublish
Résumé
Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery. One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb. The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD. The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.
Sections du résumé
BACKGROUND
BACKGROUND
Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery.
METHODS
METHODS
One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb.
DISCUSSION
CONCLUSIONS
The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD.
TRIAL REGISTRATION
BACKGROUND
The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.
Identifiants
pubmed: 39415284
doi: 10.1186/s13063-024-08515-w
pii: 10.1186/s13063-024-08515-w
doi:
Substances chimiques
Anesthetics, Inhalation
0
Sevoflurane
38LVP0K73A
Anesthetics, Intravenous
0
Propofol
YI7VU623SF
S100 Calcium Binding Protein beta Subunit
0
Biomarkers
0
Inflammation Mediators
0
S100B protein, human
0
Types de publication
Journal Article
Clinical Trial Protocol
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
684Informations de copyright
© 2024. The Author(s).
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