Effect of nitric oxide on renal injury in children undergoing surgical correction of congenital septal heart defects under cardiopulmonary bypass: a singlecenter randomized prospective pilot clinical trial

Acute kidney injury (AKI) remains a common and prognostically unfavorable complication of cardiac surgery in children performed under cardiopulmonary bypass (CPB). Nitric oxide (NO), a universal endogenous vasodilator and cytoprotector, has the potential to mitigate key mechanisms of AKI. However, in pediatric practice data are lacking regarding the safety and efficacy of targeted intraoperative NO delivery into the CPB circuit for AKI prevention.

Aim: To assess the safety and potential nephroprotective effect of delivering nitric oxide (80 ppm) directly into the cardiopulmonary bypass circuit during surgical correction of congenital septal heart defects in children.

Material and Methods. A pilot randomized study was conducted. Thirty patients were divided into two groups: the study group (n = 15) received 80 ppm NO during CPB, and the control group (n = 15) did not receive NO. Safety was assessed by methemoglobin levels and clinical course. Efficacy was analyzed by the dynamics of specific AKI biomarkers (NGAL, IL-18) in blood and urine before surgery, after CPB, and at 16 hours, by changes in urinary oxygen tension (PuO2), and by postoperative stratification using the pRIFLE criteria.

Results. Nitric oxide delivery into the extracorporeal circuit during cardiopulmonary bypass is recognized as safe: the methemoglobin level in the NO group did not exceed reference values (1.5% [1.35; 1.62]). No statistically significant differences were found in intraand postoperative clinical outcomes between the groups. Preliminary signs of potential nephroprotective efficacy were demonstrated: despite a comparable distribution of patients by pRIFLE stages (p > 0.05), the NO group showed significantly lower concentrations of blood NGAL after CPB (352.4 [254.3; 417.1] vs. 599 [430.6; 676.7] ng/ml, p = 0.03) and at 16 hours (p = 0.01), as well as in urine at all postoperative time points (p = 0.001). The interleukin-18 (IL-18) level at 16 hours was also significantly lower in the intervention group, both in blood (4.14 [2.49; 6.01] vs. 7.4 [4.56; 7.58] pg/ml, p = 0.02) and in urine (8.31 [7.57; 10.28] vs. 13.2 [8.57; 16.2] pg/ml, p = 0.047). The urinary oxygen tension (PuO2) after CPB was significantly higher in the NO group (138.0 [96.5; 151.6] vs. 60.7 [57.2; 97.4] mmHg, p = 0.03).

Conclusion. Intraoperative donation of nitric oxide at a concentration of 80 ppm is a safe technique in children. The obtained data on its positive effect on a panel of early renal injury biomarkers (NGAL, IL-18) and renal oxygenation (PuO2) against a comparable clinical pRIFLE profile suggest it is a promising nephroprotective method, warrants further investigation in larger trials.

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