Medical Student Dalhousie University Halifax, Nova Scotia, Canada
Background: Cardiopulmonary bypass (CPB) during cardiac surgery is associated with systemic inflammation and coagulopathy, contributing to post-operative morbidity. The role of modified ultrafiltration (MUF) as an effective immunomodulatory therapy is unclear. This study aims to examine inflammatory mediator concentration changes through MUF in a pediatric cardiac surgery population.
METHODS AND RESULTS:
Methods: This sub-analysis of a prospective study (NCT05154864) on 40 pediatric cardiac surgery patients using CPB and sub-zero balance continuous ultrafiltration. Concentrations of 33 inflammatory mediators (complement, chemokines, cytokines, adhesion molecules) were analyzed by Luminex. Patient serum(s) and MUF effluent were examined Pre-MUF and Post-MUF. Within-individual magnitude of mediator concentration change of s-Post-MUF relative to s-Pre-MUF baseline was expressed as a median fold-change (FC), ([s-Post-MUF]–[s-Pre-MUF]/[s-Pre-MUF]) with [95% confidence interval] estimated by 1000 non-parametric bootstrap samples. Adjusting for hemoconcentration alone, predicted s-Post-MUF mediator concentration change (Figure1 red line) was calculated with C1V1=C2V2 principle, multiplying the observed s-Pre-MUF concentrations by MUF hemoconcentration factor (Estimated Patient Circulating Blood Volume/(Estimated Patient Circulating Blood Volume–MUF Volume)). For mediators extracted during MUF, mediator mass extraction fraction was calculated using measured concentrations and estimated patient circulating blood volumes: (Mediator Mass in MUF Effluent/(Mediator Mass in MUF Effluent + Mediator Mass in Patient Serum)). Statistical analysis used Wilcoxon signed rank test with alpha p=0.05.
Results: C3a concentration was the only decreased serum mediator after MUF (FC=-0.11[-0.21–0.00](p=0.02)). C2(FC=0.22 [0.05–0.35]), CCL2(FC=0.59 [0.33–0.78]), CCL4(FC=0.16 [0.02–0.35]), IL-1Ra(FC=0.28 [0.10–0.48]), IL-6(FC=1.28 [0.82–1.91]), IL-8(FC=0.70 [0.34–1.06]), P-selectin(FC=0.21 [0.04–0.27]), and ICAM1(FC=[0.02–0.24]) had statistically significant increase after MUF. Most mediators had observed- [Post-MUF] within the predicted-[Post-MUF] ranges, while mediators IL-6, IL-8, and CCL2 increased more than predicted(Figure1). C3a mediator extraction fraction was 71%[62%–79%]; all other mediators were < 11%.
Conclusion: Inflammatory mediator concentrations primarily increased in patients post-MUF due to hemoconcentration; IL-6, IL-8 and CCL2 increased substantially more than expected through the systemic inflammatory reaction to CPB and myocardial ischemia-reperfusion. Only C3a was meaningfully extracted in the MUF effluent, with a corresponding decrease in circulating concentration following the therapy. A minuscule amount of the other 32 mediators were extracted by MUF and lacked a correlated reduction in circulating concentration. Our findings challenge the popular opinion that MUF has a broad immunomodulatory effect.
