Sanguineous cardiopulmonary bypass prime accelerates the inflammatory response during pediatric cardiac surgery

Background: The inflammatory response to cardiopulmonary bypass (CPB) in pediatric patients remains an unresolved challenge. Sanguineous CPB prime, composed of allogenic blood products, is one potentially important stimulus. This study aims to identify specific inflammatory mediators active in sanguineous CPB prime and their impact on the inflammatory response at CPB initiation.

Methods: In a post-hoc analysis of a prospective observational cohort study (NCT05154864), where pediatric patients undergoing cardiac surgery with CPB were enrolled after informed consent, patients were grouped by CPB prime type (sanguineous vs crystalloid). Arterial samples were collected post-sternotomy as a baseline and again at CPB initiation from all patients. In the sanguineous group, CPB prime samples were also collected after buffered ultrafiltration but before CPB initiation. Luminex® measured concentrations of 24 inflammatory mediators for comparison between groups. Statistical analyses were by Mann-Whitney test and Wilcoxon signed-rank test. Data are presented as median [IQR].

Results: Forty consecutive pediatric patients participated. The sanguineous group (n = 26) was younger (4.0 [0.2 - 6.0] vs 48.5 [39.0 - 69.5] months; p = 2.6 × 10^-7) and smaller (4.9 [34 - 6.6] vs 17.2 [14.9 - 19.6] kg; p = 2.6 × 10^-7) than the crystalloid group (n = 14). Despite this, baseline concentrations of 20 complement and cytokine concentrations were comparable between groups (p > 0.05) while four showed differences between groups (p < 0.05). The sanguineous prime contained supraphysiologic concentrations of complement mediators: C2, C3, C3a, C3b, and C5a. Correspondingly, upon CPB initiation, patients receiving sanguineous prime exhibited a significantly larger burden of C2, C3, C3b, C5, and C5a (p < 0.001) relative to the crystalloid group. Cytokine and chemokine mediators were present at trace levels in the sanguineous prime.

Conclusions: Sanguineous prime contains activated complement that accelerates the inflammatory response at CPB initiation in neonates and infants. Immunomodulatory interventions targeting complement during CPB prime preparation could offer substantial benefits for these vulnerable patients.