Cardiopulmonary bypass (CPB) provokes a systemic inflammatory response with important consequences for infants and children undergoing repair of congenital heart disease [[1], [2], [3]]. Inflammation engages overlapping coagulation and immune cascades that can culminate in endothelial dysfunction, vasoplegia, and organ injury, contributing to postoperative morbidity and delayed recovery in a substantial subset of patients [[4], [5], [6], [7], [8], [9]].

Efforts to blunt the postoperative inflammatory response in children have largely used global modulation strategies—biocompatible, heparin-coated circuits, nitric oxide delivered into the circulation, perioperative corticosteroids, and modified ultrafiltration—but clinical benefits have been inconsistent . By contrast, targeted cytokine therapies in other hyperinflammatory conditions—tocilizumab (Interleukin (IL)-6 receptor blockade) [15], anakinra (IL-1 receptor antagonist) [16], and infliximab or etanercept (Tumor necrosis factor alpha (TNF-α) inhibitors) —show clear clinical utility. These successes highlight the promise of precision immunomodulation in pediatric cardiac surgery, if relevant pathways are delineated.

We therefore conducted a systematic review to synthesize cytokine measurements after pediatric cardiopulmonary bypass, characterize temporal patterns across prespecified postoperative windows, and evaluate certainty of evidence. Our aim was to identify reliable postoperative signals—particularly potential anchor biomarkers—that could inform standardized measurement, link profiles to outcomes, and enable rational design and timing of mechanism-based anti-inflammatory trials.