Preliminary Study of Serum Biomarkers Associated With Delirium After Major Cardiac Surgery

OBJECTIVES: The objective of this study was to identify novel serum biomarkers specific to postoperative delirium following major cardiac surgery to provide insight into the pathological 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: Twenty-four older adults (>60 years old) undergoing major cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a positive screen for delirium from postoperative day 1 through 3 based on criteria included in the long form of the Confusion Assessment Method. We applied a multiplexed proteomic approach using proximity extension assays to identify and quantify proteins found in serum collected on the day of surgery and postoperative day 1 in delirious and non-delirious patient cohorts. We identified an increase in serum fibroblast growth factor (FGF)-21 levels in the delirious cohort from a pre-surgery baseline of (mean ±stdev) 5.0 (±1.1) log2 abundance (95% confidence interval (CI) [4.3 to 5.7]) to 6.7 (±1.6) log2 abundance (95% CI [5.7 to 7.7], p=0.01) post-surgery. We identified a similar increase in FGF-23 from a pre-surgery baseline of 1.7 (±1.3) log2 abundance (95% CI [0.8 to 2.5]) to 3.4 (±2.2) log2 abundance (95% CI [2.0 to 4.8]), p=0.06) post-surgery. We also identified an increase in interleukin-6 serum levels in the delirious cohort from a pre-surgery baseline of 3.8 (±1.1) log2 abundance (95% CI [3.1 to 4.5]) to 8.7 (±1.9) log2 abundance (95% CI [7.5 to 9.9], p