Objectives
The objective of this study was to identify novel serum biomarkers specific to postoperative
delirium after major cardiac surgery to provide insight into the pathologic processes
involved in delirium and its sequelae.
Design
Nested, case-control study.
Setting
Cardiac surgical intensive care unit in a single-site hospital setting.
Participants
The study comprised 24 older adults (aged >60 years) undergoing major cardiac surgery
with cardiopulmonary bypass.
Interventions
None.
Measurements and Main Results
The primary outcome was a positive screen for delirium from postoperative days one
through three based on criteria included in the long form of the Confusion Assessment
Method. A multiplexed proteomic approach was applied using proximity extension assays
to identify and quantify proteins found in serum collected on the day of surgery and
postoperative day one in delirious and nondelirious patient cohorts. An increase in
serum fibroblast growth factor (FGF)-21 levels was identified in the delirious cohort
from a presurgery baseline of (mean ± standard deviation) 5.0 ± 1.1 log2 abundance
(95% confidence interval [CI], 4.3-5.7) to 6.7 ± 1.6 log2 abundance (95% CI, 5.7-7.7;
p = 0.01) postsurgery. A similar increase was identified in FGF-23 from a presurgery
baseline of 1.7 ± 1.3 log2 abundance (95% CI, 0.8-2.5) to 3.4 ± 2.2 log2 abundance
(95% CI, 2.0-4.8; p = 0.06) postsurgery. An increase in interleukin-6 serum levels also was identified
in the delirious cohort from a presurgery baseline of 3.8 ± 1.1 log2 abundance (95%
CI, 3.1-4.5) to 8.7 ± 1.9 log2 abundance (95% CI, 7.5-9.9; p < 0.0001) postsurgery. However, the increase in interleukin-6 serum levels of the
nondelirious cohort also met the study's threshold for statistical significance (p < 0.0001). Finally, an increase in monocyte chemotactic protein-3 serum levels was
identified in the delirious cohort from a presurgery baseline of 4.1 ± 0.9 log2 abundance
(95% CI, 3.6-4.7) to 6.1 ± 2.0 log2 abundance (95% CI, 4.8-7; p = 0.009) postsurgery.
Conclusions
FGF-21, FGF-23, interleukin-6, and monocyte chemotactic protein-3 serum levels were
increased postoperatively in patients who developed delirium after major cardiac surgery.
This study identified two members of the FGF family as potential putative systemic
biomarkers for postoperative delirium after cardiac surgery, suggesting a possible
role for metabolic recovery in the pathophysiologic mechanisms underlying neurocognitive
dysfunction.
Key Words
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Article info
Publication history
Published online: May 12, 2021
Footnotes
The project was supported by the National Institutes of Health and National Institute on Aging (R01AG053582) (O.A.) and research funds from the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital (O.A.).
Identification
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