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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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The Association of Postoperative Cognitive Dysfunction With Glymphatic Function and Neuroinflammation, The Association of Postoperative Cognitive Dysfunction With CSF Metabolomic Change

Intervention / Treatment
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* Drug: Dexmedetomidine
* Device: anesthesia depth monitoring


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two interventional group with BIS group and DEX group all receive BIS monitoring, and DEX group receive dexmedetomidine infusion.
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative cognitive function | MMSE, MoCA, CAM-ICU score | postoperative 2 hours, postoperative day 1, postoperative day 2, postoperative day 3 | 
| NMR amd LC-MS CSF and plasma metabolomics | NMR and LC-MS metabolomics of CSF and plasma samples | preoperative, postoperative 2 hours, postoperative day 1 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anesthesia depth monitoring, postoperative cognitive dysfunction, metabolomics, cerebrospinal fluid, glymphatic function