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

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.

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huan-Tang Lin, MD; Phone Number: 2324 +886-33281200; Email: sanctuary12@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
    • Contact: Huan-tang Lin; Phone Number: 2324 033281200; Email: sanctuary12@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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.	Device: anesthesia depth monitoring; intraoperative anesthesia depth monitoring to keep BIS 40-60; Other Names: BIS; Drug: Dexmedetomidine; dexmedetomidine infusion; Other Names: DEX
No Intervention: Usual group; usual care with 1 MAC sevoflurane maintainance.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Huan-tang Lin, Department of anesthesiology, Linkou Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: cerebrospinal fluid; postoperative cognitive dysfunction; metabolomics; anesthesia depth monitoring; glymphatic function
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Inflammation; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications; Neuroinflammatory Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: CMRPG3N0591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: personal data is encrypted

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No