Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery

Recruiting

• Conditions: Thoracic Aortic Aneurysm; Postoperative Cognitive Dysfunction; Postoperative Delirium
• Interventions: Diagnostic Test: Trajectory of neuroinflammatory proteins in CSF and blood

• Registration Number: NCT04523909
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Observational prospective pilot study to analyze the trajectory of neuroinflammatory protein expression in cerebrospinal fluid (CSF) in relation to systemic compartment in patients undergoing thoracic aortic surgery.

The aim of this study is to identify and unravel the biochemical (neuroinflammatory) pathways involved in postoperative delirium.

Patient undergoing thoracic aortic surgery will have an external lumbar drain (ELD) in situ on the day before surgery. This ELD remains in place during and three days after surgery to reduce the risk on periprocedural spinal cord ischemia. Paired measurements of CSF and blood will be analyzed.

Detailed Description

Major (cardiovascular) surgery is frequently associated with cerebral dysfunction postoperatively. Major surgical procedures account for substantial systemic inflammatory activation. Interestingly, animal models have shown that surgery rather than anaesthetics trigger a neurocognitive decline. An increase of pro-inflammatory cytokines and activation of immune cells mediate this post operative cognitive decline. There is growing support that systemic inflammation can activate the innate immune system of the brain leading to inflammation in the brain ('neuroinflammation'). This neuroinflammation is suggested to play a pivotal role in postoperative delirium and postoperative cognitive decline due to surgery-related systemic inflammation. However little evidence is available on the extend of the neuroinflammation and which biochemical pathways are dysregulated in the brain after surgery.

Thoracic aortic surgery offers the unique opportunity to study the trajectory of protein expression in CSF prior to and after surgery in a non-invasive matter. It is standard of care that an external lumbar drain (ELD) is placed the day prior to surgery and this ELD will remain in place during three postoperative days.

To advance the understanding of the impact of major surgery to the brain, the investigators wish to study the trajectory of protein expression prior to and after thoracic aortic surgery.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2017-12-18
• Study First Submitted: 2019-05-06
• Study First Submitted QC: 2020-08-19
• Study First Posted: 2020-08-24
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-28
• Last Update Posted: 2023-03-31
• Primary Completion: 2025-12-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Competent patients ≥ 18 years
• Patients who will undergo thoracic aortic surgery and will therefore receive an external lumbar drain as a standard of care procedure.

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Exclusion Criteria

• Patients with meningitis/encephalitis/brain abscess within the last 6 months
• Patients with other neurological conditions: brain injury (acute stroke, brain trauma or cerebral haemorrhage) within the last 3 months, known brain tumours, neurodegenerative disease or known pre-existing cognitive impairment (to a degree that would be compatible with mild cognitive impairment or more).
• Brain or spinal surgery within the last 3 months
• Active infection <2 weeks before surgery
• Patients who object against storage of their body material for scientific reasons

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Thoracic aortic surgery patients	Trajectory of neuroinflammatory proteins in CSF and blood	-

Primary Outcome Measures

Name	Time	Method
Trajectory of the concentration of a panel of inflammatory proteins in CSF	9 timepoints: Baseline (immediately before surgery); Start extracorporeal circulation; Stop extracorporeal circulation (ECC); 2 hours (h) after stop ECC; 4h after stop ECC; 6h after stop ECC; 24h after baseline; 48h after baseline; 72h after baseline	Changes in CSF cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.

Secondary Outcome Measures

Name	Time	Method
Trajectory of brain injury markers in CSF	9 timepoints: Baseline to 72 hours after surgery	Changes in brain injury markers will be determined (including NFL, S100B, GFAP, UCHL1, NSE)
Trajectory of brain injury markers in plasma	9 timepoints: Baseline to 72 hours after surgery	Changes in brain injury markers will be determined (including S100B, GFAP, UCHL1, NSE)
Occurence of postoperative delirium	14-day incidence of delirium	Yes or No
Changes in ex vivo cytokine production after whole blood stimulation	5 timepoints: Baseline to 48 hours after surgery	TNF-a,IL6, IL10
Changes in mHLA-DR expression	5 timepoints: Baseline to 48 hours after surgery	monocytic HLA-DR expression assessed by flowcytometry
Trajectory of the concentration of a panel of inflammatory proteins in plasma	9 timepoints: Baseline to 72 hours after surgery	Changes in plasma cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.
Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio	9 timepoints: Baseline to 72 hours after surgery	CSF/Plasma albumine ratios will be measured for all timepoints where paired CSF/plasma samples are present

Trial Locations

Locations (1)

Department of Intensive Care Medicine, Radboud university medical center; 🇳🇱 Nijmegen, Netherlands