Abstract
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.