The immunomodulatory effect of continuous ultrafiltration during pediatric cardiac surgery

Background Cardiopulmonary bypass is associated with systemic inflammation during pediatric cardiac surgery and features elevated systemic concentrations of complement, cytokines and chemokines. The objective of this study is to quantify the immunologic efficacy of ultrafiltration (UF) used continuously throughout CPB. Methods Pediatric patients were enrolled in a single-arm prospective clinical study (NCT05154864) and received standard cardiac operations, CPB and subzero-balance ultrafiltration (SBUF) with an effluent extraction rate of 30 mL/kg/hr and conventional ultrafiltration (CUF). Paired arterial and UF effluent samples were taken at regular intervals during CPB and the concentration of 33 inflammatory mediators were measured. An exploratory counterfactual analysis assessed whether UF removed a significant amount of mediator mass using area under the curve (AUC), generalized linear mixed-effects models (GLMEM), and median fold change [95% CI] comparisons between observed data (UF) and reconstructed counterfactual data (no UF). Results Forty consecutive eligible consenting patients participated; the majority were male (58%), age of 7.3 (1.7 – 39.0) months and weight of 6.7 (4.6 – 14.9) kg. All patients received UF therapy with effluent extraction of 155 (100 – 185) ml/kg during CPB. C3a, C5a, TNF, IL-1α, IL-1β, IL-1Ra, IL-2, IL-6, IL-10, CCL2, CCL3, CCL4, CXCL1, CXCL2, CXCL8, ET1, GM-CSF and TRAIL were detected in the UF effluent. In the counterfactual analysis, only C3a was significantly extracted by UF using AUC ( p = 3.5 × 10 −12 ), GLMEM ( p = 2.3 × 10 −87 ), and median fold change [95% CI] as C3a showed a decrease of −0.2 [−0.3 to 0] relative to CPB initiation, in the observed data, compared to the counterfactual with a median fold increase of 4.3 [3.1 – 5.3]. Conclusions Ultrafiltration during pediatric CPB extracts cytokines and chemokines continuously throughout CPB with relatively low effectiveness. In an exploratory counterfactual analysis, C3a was the only inflammatory mediator meaningfully removed from the circulation by UF.