Differential Associations of Postoperative Plasma and Cerebrospinal Fluid Albumin Changes with Delirium Following Non-Cardiac Surgery
- 1Department of Anesthesiology, Duke University School of Medicine
Abstract
BACKGROUNDPostoperative increases in cerebrospinal fluid (CSF) to plasma albumin ratio (CPAR), a blood-brain barrier dysfunction marker, have been associated with postoperative delirium (POD) and prolonged hospital stay. However, the contributions of plasma versus CSF albumin changes remain unclear.
AIMTo determine whether 24-hour postoperative changes in plasma and CSF albumin are independently associated with POD and hospital length of stay.
METHODSPlasma and CSF albumin concentrations were measured before and 24-hours postoperatively in older non-cardiac surgery patients. Multivariable logistic and negative binomial regression models evaluated associations between albumin changes and POD or hospital length of stay, adjusting for age, baseline cognition, surgery type, and fluid administration.
RESULTSOf 240 patients, 31 (13.3%) developed POD. From before to 24-hours after surgery, both plasma albumin (median 3.95 to 3.43 g/dL, p<0.001) and CSF albumin decreased (median 22.68 to 20.43 mg/dL, p<0.001). Greater plasma albumin decreases (per 0.43 g/dL) were independently associated with POD (OR 2.14, 95% CI 1.28-3.58; p=0.004) and longer hospital stay (mean ratio 1.44, 95% CI 1.26-1.64; p<0.001). In contrast, CSF albumin changes (per 5.8 mg/dL higher) were not associated with POD (OR 0.97, 95% CI 0.60-1.58; p=0.91) but were modestly associated with longer hospital stay (mean ratio 1.17, 95% CI 1.04-1.32; p=0.01).
CONCLUSIONSPlasma and CSF albumin decreased postoperatively, but only plasma decreases were associated with POD. These results suggest that associations between CPAR increases and POD may be due to postoperative plasma albumin decreases and highlight limitations of CPAR as a standalone marker of postoperative BBB dysfunction.
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BibTeX
@misc{hassan2026differential,
title = {{Differential Associations of Postoperative Plasma and Cerebrospinal Fluid Albumin Changes with Delirium Following Non-Cardiac Surgery}},
author = {R. Hassan and L. Sant'Ana Dumont and M. Cooter Wright and J. Takla and K. Monten and S. Teshome and E. R. Marcantonio and N. Terrando and J. N. Browndyke and H. E. Whitson and H. J. Cohen and A. G. Nackley and M. K. Wong and M. E. Klein and P. C. Boykin and N. J. Timko and M. Muehlbauer and E. W. Ely and J. P. Mathew and M. Berger and M. Devinney},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.26363418},
url = {https://www.medrxiv.org/content/10.64898/2026.09.18.26363418v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Differential Associations of Postoperative Plasma and Cerebrospinal Fluid Albumin Changes with Delirium Following Non-Cardiac Surgery
AU - R. Hassan
AU - L. Sant'Ana Dumont
AU - M. Cooter Wright
AU - J. Takla
AU - K. Monten
AU - S. Teshome
AU - E. R. Marcantonio
AU - N. Terrando
AU - J. N. Browndyke
AU - H. E. Whitson
AU - H. J. Cohen
AU - A. G. Nackley
AU - M. K. Wong
AU - M. E. Klein
AU - P. C. Boykin
AU - N. J. Timko
AU - M. Muehlbauer
AU - E. W. Ely
AU - J. P. Mathew
AU - M. Berger
AU - M. Devinney
PY - 2026
DA - 2026/09/18
PB - medRxiv
DO - 10.64898/2026.09.18.26363418
UR - https://www.medrxiv.org/content/10.64898/2026.09.18.26363418v1
AB - BACKGROUNDPostoperative increases in cerebrospinal fluid (CSF) to plasma albumin ratio (CPAR), a blood-brain barrier dysfunction marker, have been associated with postoperative delirium (POD) and prolonged hospital stay. However, the contributions of plasma versus CSF albumin changes remain unclear. AIMTo determine whether 24-hour postoperative changes in plasma and CSF albumin are independently associated with POD and hospital length of stay. METHODSPlasma and CSF albumin concentrations were measured before and 24-hours postoperatively in older non-cardiac surgery patients. Multivariable logistic and negative binomial regression models evaluated associations between albumin changes and POD or hospital length of stay, adjusting for age, baseline cognition, surgery type, and fluid administration. RESULTSOf 240 patients, 31 (13.3%) developed POD. From before to 24-hours after surgery, both plasma albumin (median 3.95 to 3.43 g/dL, p<0.001) and CSF albumin decreased (median 22.68 to 20.43 mg/dL, p<0.001). Greater plasma albumin decreases (per 0.43 g/dL) were independently associated with POD (OR 2.14, 95% CI 1.28-3.58; p=0.004) and longer hospital stay (mean ratio 1.44, 95% CI 1.26-1.64; p<0.001). In contrast, CSF albumin changes (per 5.8 mg/dL higher) were not associated with POD (OR 0.97, 95% CI 0.60-1.58; p=0.91) but were modestly associated with longer hospital stay (mean ratio 1.17, 95% CI 1.04-1.32; p=0.01). CONCLUSIONSPlasma and CSF albumin decreased postoperatively, but only plasma decreases were associated with POD. These results suggest that associations between CPAR increases and POD may be due to postoperative plasma albumin decreases and highlight limitations of CPAR as a standalone marker of postoperative BBB dysfunction.
ER -