Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery
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An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Trajectory of neuroinflammatory proteins in CSF and blood.
- Who it may be relevant to
- Registry conditions: Postoperative Delirium, Postoperative Cognitive Dysfunction, Thoracic Aortic Aneurysm. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery: the TURBO Study
Overview
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.
Interventions
- Diagnostic test Trajectory of neuroinflammatory proteins in CSF and blood
Kinetics of neuroinflammatory markers in CSF and blood
Primary outcome measures
- Trajectory of the concentration of a panel of inflammatory proteins in CSF [Time frame: 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]
Secondary outcome measures (7)
- Trajectory of the concentration of a panel of inflammatory proteins in plasma [Time frame: 9 timepoints: Baseline to 72 hours after surgery]
- Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio [Time frame: 9 timepoints: Baseline to 72 hours after surgery]
- Occurence of postoperative delirium [Time frame: 14-day incidence of delirium]
- Trajectory of brain injury markers in CSF [Time frame: 9 timepoints: Baseline to 72 hours after surgery]
- Trajectory of brain injury markers in plasma [Time frame: 9 timepoints: Baseline to 72 hours after surgery]
- Changes in ex vivo cytokine production after whole blood stimulation [Time frame: 5 timepoints: Baseline to 48 hours after surgery]
- Changes in mHLA-DR expression [Time frame: 5 timepoints: Baseline to 48 hours after surgery]
Eligibility criteria
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.
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Netherlands · 1 center
- Department of Intensive Care Medicine, Radboud university medical center — Nijmegen
Identifiers
NCT: NCT04523909 · CMO 2017-3774