A Clinical Feasibility Study to Establish a Customized Panel of Biomarkers for Inflammation and Endothelial Dysfunction in Pediatric Cardiac Surgery

Background: Cold-inducible RNA binding Protein (CIRBP) has previously been described as novel biomarker for inflammation. As systemic inflammatory response syndrome (SIRS) and capillary leak syndrome (CLS) represent frequent complications after pediatric cardiac surgery, we aimed to analyze CIRBP as well as a panel of established markers for endothelial dysfunction and inflammation in pediatric patients undergoing cardiac surgery.

Methods: We conducted a prospective observational clinical study during a period of 9 months starting in May 2020. Patients up to 18 years of age with congenital heart disease (CHD) undergoing cardiac surgery at our center were enrolled. Serum samples were collected before the surgery, upon arrival at the pediatric intensive care unit, as well as 6 and 24 hours after surgery. Magnetic bead-based immunoassay panels were custom designed to analyze CIRBP, interleukin-1b (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), monocyte chemotactic protein 1 (MCP-1), Syndecan-1 (SDC-1), Thrombomodulin (TM), vascular endothelial growth factor (VEGF-A-A), Angiopoietin-2 (Ang-2) and fibroblast growth factor 23 (FGF-23) in 25 µL serum using the MAGPIX system. Statistical analysis was conducted using Wilcoxon rank sum test with Bonferroni correction to compare postoperative with the preoperative biomarker concentrations.

Results: A total of 19 patients were enrolled in our feasibility study including 10 males and 9 female patients (median age 2.9 years). All investigated biomarkers were detectable in the small 25 µL serum volume. We observed a trend in increased CIRBP concentrations after the operation relative to baseline but did not reach significance. Proinflammatory cytokines IL-6, IL-8, IL10, as well as biomarker for endothelial dysfunction Ang-2 concentration increased significantly after surgery, remaining elevated in all postoperative time points investigated. SDC-1, TM, and MCP-1 concentrations were also significantly elevated directly after surgery but returned to baseline levels 6h or 24 hours after surgery.

Conclusion: In this clinical feasibility study we were able to analyze CIRBP concentrations as well as a representative panel of biomarkers for inflammation and endothelial dysfunction in a minimal sample volume. Although, postoperative increase of CIRBP did not reach significancy, perhaps due to the small patient number, further investigation is warranted. To our knowledge this is the first clinical study to assess CIRBP as a potential biomarker for inflammation in a pediatric population.

Publication History

Article published online:
13 February 2024