(P079) SANGUINEOUS CARDIOPULMONARY BYPASS PRIME ACCELERATES THE INFLAMMATORY RESPONSE DURING PEDIATRIC CARDIAC SURGERY

Background:

Background: The inflammatory response to cardiopulmonary bypass (CPB) in pediatric patients contributes to post-operative morbidity and remains an unresolved challenge. Sanguineous prime, composed of donated red blood cells and fresh frozen plasma, is used for small patients to prevent excessive hemodilution at CPB initiation. This study aims to identify prevalent inflammatory mediators in sanguineous CPB prime and the corresponding immunologic impact at CPB initiation.

METHODS AND RESULTS: A post-hoc analysis of a prospective observational cohort study (NCT05154864) investigating pediatric patients undergoing cardiac surgery with CPB. This retrospective analysis compared patients by CPB prime type (sanguineous vs. crystalloid). In the sanguineous group, CPB prime samples were collected before CPB initiation. Patient arterial samples were collected post-sternotomy as a baseline and again at CPB initiation from all patients. Luminex® determined concentrations of twenty-four inflammatory mediators. Mediator concentrations in the crystalloid prime were assumed to be 0. Data are presented as median [IQR]. Statistical comparisons were made using the Mann-Whitney test and Wilcoxon signed-rank test.

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 x 10-7), smaller (4.9 [34 – 6.6] vs. 17.2 [14.9 – 19.6] kg; p = 2.6 x 10-7) and had a higher proportion of STAT 3 & 4 pathologies (58% vs. 0%; p = 1.5 x 10-3) than the crystalloid group (n=14). Despite these demographic differences, baseline concentrations of C1q, C2, C3, C3a, C3b, C4, C5, C5a, CFB, CFH, TNF, IL-1α, IL-1β, IL-10, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL8 were comparable between groups (p > 0.05). Baseline C4b and CFI were higher in the crystalloid group, while baseline IL-6 and IL-1RA were more prominent in the sanguineous group (p < 0.05). The sanguineous prime contained supraphysiologic concentrations of complement mediators: C2, C3, C3a, C3b, C5, and C5a. Correspondingly, upon CPB initiation, patients receiving sanguineous prime exhibited a significantly larger complement burden relative to the crystalloid group (Figure 1). Cytokine and chemokine mediators were present at trace levels in the sanguineous prime and underwent hemodilution upon CPB initiation in both groups.

Conclusion: Sanguineous prime contains an enormous burden of activated complement, accelerating the inflammatory reaction at CPB initiation. Prior research has suggested that complement activation is associated with post-operative morbidity and prolonged recovery. Therefore, developing complement-specific immunomodulatory interventions during CPB prime preparation could offer substantial clinical benefits and enhanced recovery for these vulnerable patients.