CSF Metabolomics and Glymphatic Function in Patients Receiving VP- Shunt Surgery.

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT06005363

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this randomized control study, the investigators intended to evaluate the influence of different anesthetics on postoperative cognitive dysfunction, neuroinflammation, CSF metabolomics, and glymphatic function in patients with normal pressure hydrocephalus for VP shunt surgery. The investigators assume that the use of dexmedetomidine infusion and proper anesthsia depth during general anesthesia, in addition to multi-model analgesia, might be helpful to enhance glymphatic function, reduce neuroinflammation, and decrease postoperative cognitive dysfunction.

Condition or Disease	Intervention/Treatment	Phase
The Association of Postoperative Cognitive Dysfunction With Glymphatic Function and Neuroinflammation The Association of Postoperative Cognitive Dysfunction With CSF Metabolomic Change	Drug: Dexmedetomidine Device: anesthesia depth monitoring	N/A

Detailed Description

In this prospective randomized controlled study, 48 patients with communicating hydrocephalus will be enrolled in the study and these patients will be divided into 3 groups in which intervention group received anesthesia depth monitoring (BIS group and DEX group) and dexmedetomidine infusion (DEX group), while the controlled group received usual anesthesia care without dexmedetomidine during VP shunt surgery. The participant's intraoperative CSF and plasma samples will be collected for biochemical analysis and metabolomic analysis. The investigators will use two analytical metabolomic platforms, including nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), to execute quantitative metabolomics on human CSF and plasma samples. These metabolomic data will be compared with previous established human aging CSF Metabolome Database. After VP shunt surgery, these patient's glymphatic function will be evaluated with 3T functional MRI. The postoperative cognitive function and delirium status of these patients will be evaluated for the following 3 days using MMSE score, Montreal Cognitive Assessment, and CAM-ICU score. During analysis, the pre-operative metabolomic signature of patients with postoperative cognitive dysfunction(POCD) will be compared with patients without POCD to profile the metabolomics of POCD. Besides, the investigators could examine the correlation of glymphatic function and POCD. By comparing the CSF metabolomic change in these three groups, the investigators could evaluate the the efficacy of anesthesia depth monitoring and dexmedetomidine to reduce POCD development during VP shunt surgery. The result of this study might be able to explain the brain pathophysiology of POCD, the role of glymphatic function in POCD, metabolomic signature of POCD, and establish a better anesthesia regimen to reduce the development of POCD.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two interventional group with BIS group and DEX group all receive BIS monitoring, and DEX group receive dexmedetomidine infusion.Two interventional group with BIS group and DEX group all receive BIS monitoring, and DEX group receive dexmedetomidine infusion.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Participants receive randomized allocation to BIS, DEX, or usual care group before VP shunt surgery. Outcome assessor evaluate the preoperative and postoperative cognitive function, delirium status, and evaluate glymphatic function with functional MRI.

Primary Purpose:

Diagnostic

Official Title:

The Application of Anesthesia Depth Monitoring on Post-operative Cognitive Dysfunction for Patients With Hydrocephalus Receiving Ventricular-peritoneal Shunt Surgery and Associated Change in CSF Metabolomics and Glymphatic Function.

Actual Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2026

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BIS group Use BIS monitoring to adjust intraoperative anesthetics.	Device: anesthesia depth monitoring intraoperative anesthesia depth monitoring to keep BIS 40-60 Other Names: BIS
Experimental: DEX group use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.	Drug: Dexmedetomidine dexmedetomidine infusion Other Names: DEX Device: anesthesia depth monitoring intraoperative anesthesia depth monitoring to keep BIS 40-60 Other Names: BIS
No Intervention: Usual group usual care with 1 MAC sevoflurane maintainance.

Arm

Intervention/Treatment

Experimental: BIS group

Use BIS monitoring to adjust intraoperative anesthetics.

Device: anesthesia depth monitoring

intraoperative anesthesia depth monitoring to keep BIS 40-60

Other Names:

BIS

Experimental: DEX group

use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.

Drug: Dexmedetomidine

dexmedetomidine infusion

Other Names:

DEX

Device: anesthesia depth monitoring

intraoperative anesthesia depth monitoring to keep BIS 40-60

Other Names:

BIS

No Intervention: Usual group

usual care with 1 MAC sevoflurane maintainance.

Outcome Measures

Primary Outcome Measures

Postoperative cognitive function [postoperative 2 hours, postoperative day 1, postoperative day 2, postoperative day 3]
MMSE, MoCA, CAM-ICU score
NMR amd LC-MS CSF and plasma metabolomics [preoperative, postoperative 2 hours, postoperative day 1]
NMR and LC-MS metabolomics of CSF and plasma samples

Secondary Outcome Measures

Neuroinflammation parameters [preoperative, postoperative 2 hours, postoperative day 1]
lactate, tau protein, amyloid beta, orexin, IL-6, IL-10, TNF-alpha, s100b
Glymphatic function [preoperative, postoperative day 1]
evaluate DTI-ALPS index in 3T functional MRI

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with communicating hydrocephalus for elective VP shunt surgery under general anesthesia
age> 60 y/o
conscious clear
fluency in Chinese
anticipated hospital stay ≥ 3 days after surgery

Exclusion Criteria:

unstable preoperative condition (unstable angina, CHF, asthma attack) within 4 weeks before surgery,
severe hepatic dysfunction or renal failure
history of neuropsychological diseases such as schizophrenia, Parkinson's disease, dementia, stroke,
pre-op cognitive impairment,
preoperative delirium,
preoperative depression,
allergy to contrast medium of MRI.