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

Not Applicable

Recruiting

• Conditions: The Association of Postoperative Cognitive Dysfunction With CSF Metabolomic Change; The Association of Postoperative Cognitive Dysfunction With Glymphatic Function and Neuroinflammation
• Interventions: Device: anesthesia depth monitoring; Drug: Dexmedetomidine

• Registration Number: NCT06005363
• Lead Sponsor: Chang Gung Memorial Hospital

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.

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 Timeline

• Study Start: 2023-07-01
• Status Verified: 2023-08
• Study First Submitted: 2023-08-07
• Study First Submitted QC: 2023-08-17
• Last Update Submitted: 2023-08-17
• Study First Posted: 2023-08-22
• Last Update Posted: 2023-08-22
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIS group	anesthesia depth monitoring	Use BIS monitoring to adjust intraoperative anesthetics.
DEX group	Dexmedetomidine	use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.
DEX group	anesthesia depth monitoring	use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.

Primary Outcome Measures

Name	Time	Method
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
Postoperative cognitive function	postoperative 2 hours, postoperative day 1, postoperative day 2, postoperative day 3	MMSE, MoCA, CAM-ICU score

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taoyuan, Taiwan