Role of Blood–Brain Barrier Dysfunction in Delirium following Non‐cardiac Surgery in Older Adults

Author:

Devinney Michael J.123ORCID,Wong Megan K.4,Wright Mary Cooter1,Marcantonio Edward R.5,Terrando Niccolò167,Browndyke Jeffrey N.8ORCID,Whitson Heather E.239,Cohen Harvey J.239,Nackley Andrea G.1,Klein Marguerita E.1,Ely E. Wesley10,Mathew Joseph P.1,Berger Miles123,

Affiliation:

1. Department of Anesthesiology Duke University School of Medicine Durham NC USA

2. Duke Center for the Study of Aging and Human Development Duke University Medical Center Durham NC USA

3. Duke/University of North Carolina Alzheimer's Disease Research Center Duke University Durham NC USA

4. School of Medicine Duke University Durham NC USA

5. Division of General Medicine and Gerontology, Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School Boston MA USA

6. Department of Cell Biology Duke University School of Medicine Durham NC USA

7. Department of Immunology Duke University School of Medicine Durham NC USA

8. Department of Psychiatry and Behavioral Sciences Duke University School of Medicine Durham NC USA

9. Division of Geriatric Medicine, Department of Medicine Duke University School of Medicine Durham NC USA

10. Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Tennessee Valley Veteran's Affairs Geriatric Research Education Clinical Center Nashville TN USA

Abstract

ObjectiveAlthough animal models suggest a role for blood–brain barrier dysfunction in postoperative delirium‐like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood–brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.MethodsCognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non‐cardiac, non‐neurologic surgery. Blood–brain barrier dysfunction was assessed using the cerebrospinal fluid‐to‐plasma albumin ratio (CPAR).ResultsOf 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = −0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [−0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03–1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09–1.22, p < 0.001).InterpretationPostoperative increases in blood–brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood–brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024–1035

Funder

National Institutes of Health

Society for Neuroscience in Anesthesiology and Critical Care

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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