Association of preoperative to postoperative change in cerebrospinal fluid fibrinogen with postoperative delirium

Thomas Payne; Jennifer Taylor; David Kunkel; Katherine Konieczka; Frankie Ingram; Kaj Blennow; Henrik Zetterberg; Robert A Pearce; Anke Meyer-Franke; Niccolò Terrando; Katerina Akassoglou; Robert D Sanders; Richard C Lennertz

doi:10.1016/j.bjao.2024.100349

Association of preoperative to postoperative change in cerebrospinal fluid fibrinogen with postoperative delirium

BJA Open. 2024 Oct 5:12:100349. doi: 10.1016/j.bjao.2024.100349. eCollection 2024 Dec.

Authors

Thomas Payne^{1

2}, Jennifer Taylor^{1

2}, David Kunkel³, Katherine Konieczka³, Frankie Ingram³, Kaj Blennow^{4

5

6

7}, Henrik Zetterberg^{4

5

8

9

10

11}, Robert A Pearce³, Anke Meyer-Franke^{12

13}, Niccolò Terrando¹⁴, Katerina Akassoglou^{12

13

15}, Robert D Sanders^{1

2

16

17}, Richard C Lennertz³

Affiliations

¹ Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
² Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia.
³ Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁶ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
⁷ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, China.
⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹² Gladstone UCSF Center for Neurovascular Brain Immunology, San Francisco, CA, USA.
¹³ Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
¹⁴ Department of Anesthesiology, Cell Biology, and Immunology, Duke University Medical Center, Durham, NC, USA.
¹⁵ Department of Neurology and Weill Institute of Neuroscience, University of California San Francisco, San Francisco, CA, USA.
¹⁶ Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, New South Wales, Australia.
¹⁷ NHMRC Clinical Trials Centre, The University of Sydney, New South Wales, Australia.

Abstract

Background: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity.

Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair. CSF samples were obtained before (n=24) and after surgery (n=13), with some participants having multiple postoperative samples. Our primary outcome was the perioperative change in CSF fibrinogen. Delirium was assessed using the Delirium Rating Scale-Revised-98.

Results: CSF fibrinogen increased after surgery (P<0.001), and this was associated with an increase in CSF/plasma albumin ratio (β=1.09, 95% CI 0.47-1.71, P=0.004). The peak change in CSF fibrinogen was associated with the change in CSF interleukin (IL)-10 and IL-12p70. The peak change in CSF fibrinogen was associated with the change in CSF total tau (β=0.47, 95% CI 0.24-0.71, P=0.002); however, we did not observe an association with postoperative delirium severity (incidence rate ratio = 1.20, 95% CI 0.66-2.17, P=0.540).

Conclusions: Our preliminary findings support the hypothesis that fibrinogen enters the brain via blood-brain barrier disruption, promoting neuroinflammation and neuronal injury. However, we did not observe an association between cerebrospinal fluid fibrinogen and peak delirium severity in this limited cohort.

Keywords: anaesthesia; cerebrospinal fluid; delirium; fibrinogen; neurocognitive disorders; surgery.

Abstract

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