Cytokines and inflammatory biomarkers and their association with post-operative delirium: a meta-analysis and systematic review

Abstract

Delirium is a prevalent cognitive disorder among older patients and a common phenomenon following major surgical procedures. This study aimed to identify the significant proteomic biomarkers and examine their association with postoperative delirium (POD). Four electronic databases were used to identify the published articles between 1st January 2000 and 31st December 2023. Among the included 40 studies, the meta-analysis investigated 13 potential cytokines and inflammatory biomarker proteins linked with postoperative delirium. The Hedge's g standardized mean difference (SMD) was applied to calculate the effect size, with 95% confidence intervals (CIs), under the fixed effect or random effect model based on the heterogeneity index of I². Patients with POD exhibited significantly higher elevated levels of inflammatory biomarkers IL-6 (SMD = 1.45), CRP (SMD = 1.26), GFAP (SMD = 1.15), IL-1B (SMD = 0.95), IL-10 (SMD = 0.57), IL-8 (SMD = 0.56), MCP-1 (SMD = 0.39), and NFL (SMD = 0.44), suggesting that these proteins may play an inevitable role in delirium-associated cytokines and inflammatory response, development and progression of delirium. Conversely, a reduction in IGF-1 protein level (SMD = - 0.24) was also significantly associated with POD, suggesting a potential vulnerability to delirium. This study paves the way for future research aimed at early diagnosis, personalized treatment, and the development of novel therapeutic strategies to manage delirium effectively.

Keywords: C-reactive proteins; Cytokines and inflammatory proteins; Interleukins; Post-operative delirium; Systematic review and meta-analysis.

Fig. 1

The PRISMA flowchart of this study.

Fig. 2

(A) The distribution of delirium assessment methods reported in the included studies. (B) Country of Study and (C) The distribution of study types.

Fig. 3

Meta-analysis results (forest plot) for the association of the cytokines and inflammatory biomarkers proteins with delirium. The positive overall effect-size values indicate greater concentration levels among the delirium patients and negative values indicate higher concentration levels among the non-delirium. More detailed outcomes are provided in Supplementary File 3. The vertical red line (at zero point) shows the no-effect line and I² (> 50%) represents heterogeneity.

Fig. 4

The forest plot of subgroup analysis of proteins IL-6, CRP, IL-8, IL-10 and S100B (A) based on study type and (B) based on delirium assessment methods.

Fig. 4

The forest plot of subgroup analysis of proteins IL-6, CRP, IL-8, IL-10 and S100B (A) based on study type and (B) based on delirium assessment methods.