The significance of S100β and neuron-specific enolase (NSE) in postoperative cognitive dysfunction following cardiac surgery: a systematic review and meta-analysis

Abstract

Abstract Background Postoperative cognitive dysfunction (POCD) significantly affects recovery, hospitalization duration, and quality of life following cardiac surgery. Identifying reliable biomarkers for predicting POCD could improve patient outcomes and perioperative care. Among these, S100 calcium-binding protein beta (S100β) and neuron-specific enolase (NSE) have emerged as promising indicators of cerebral injury and neurocognitive dysfunction. Objectives This systematic review and meta-analysis aimed to assess within-subject perioperative changes in S100β and NSE levels among patients who developed POCD after cardiac surgery, to evaluate whether these biomarkers consistently rise in association with POCD. Methods Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science up to October 2024. Studies included peer-reviewed articles evaluating S100β and NSE levels in relation to POCD in cardiac surgery patients. Two reviewers independently extracted data and assessed the quality using the ROBINS-I tool. Meta-analyses were conducted using a random-effects model. Results Thirty studies were included. Among patients who developed POCD, both S100β and NSE levels were significantly elevated postoperatively compared to preoperative baselines. The pooled standardized mean difference (SMD) was 1.52 (95% CI 0.57–2.48; I 2 = 93.1%) for S100β and 1.19 (95% CI 0.42–1.96; I 2 = 88.7%) for NSE, indicating large effect sizes. Sensitivity analyses confirmed the robustness of these findings despite substantial heterogeneity. Conclusions Among patients who developed POCD, S100β and NSE levels significantly increased from preoperative to postoperative measurements, indicating a potential association with cerebral injury. However, as non-POCD patients were not analyzed for the same biomarker changes, causality or specificity to POCD cannot be confirmed and future research should be directed toward between group changes.

Keywords

• Postoperative cognitive dysfunction (POCD)
• S100β protein
• Neuron-specific enolase (NSE)
• Cardiac surgery
• Biomarkers
• Neurocognitive disorders