Clinical trial NCT04523909: Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery
Official title: Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery: the TURBO Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Postoperative Delirium
Postoperative Cognitive Dysfunction
Thoracic Aortic Aneurysm
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients undergoing thoracic aortic surgery who will therefore receive an external lumbar drain as a standard of care procedure.

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.

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

Primary outcomes:
measure: Trajectory of the concentration of a panel of inflammatory proteins in CSF
timeFrame: 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 outcomes:
measure: Trajectory of the concentration of a panel of inflammatory proteins in plasma
timeFrame: 9 timepoints: Baseline to 72 hours after surgery
measure: Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio
timeFrame: 9 timepoints: Baseline to 72 hours after surgery
measure: Occurence of postoperative delirium
timeFrame: 14-day incidence of delirium
measure: Trajectory of brain injury markers in CSF
timeFrame: 9 timepoints: Baseline to 72 hours after surgery
measure: Trajectory of brain injury markers in plasma
timeFrame: 9 timepoints: Baseline to 72 hours after surgery
measure: Changes in ex vivo cytokine production after whole blood stimulation
timeFrame: 5 timepoints: Baseline to 48 hours after surgery
measure: Changes in mHLA-DR expression
timeFrame: 5 timepoints: Baseline to 48 hours after surgery
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Department of Intensive Care Medicine, Radboud university medical center
Study officials:
References: