Effectiveness and Safety of Nitric Oxide in Paediatric ECMO Circuits: A Systematic Review.

Abstract

Introduction: Extracorporeal membrane oxygenation (ECMO) supports neonates and children with severe cardiac or respiratory failure, but clot formation in the circuit remains a major complication. Nitric oxide (NO), with known antiplatelet and vasodilatory effects, is being explored as an adjunct to reduce thrombosis. This systematic review aimed to evaluate the effectiveness and safety of NO delivered via ECMO sweep gas in paediatric populations. Methods: This PROSPERO-registered systematic review searched Medline, PubMed, and TRIP for published studies on nitric oxide (NO) delivered via ECMO sweep gas in paediatric patients. The primary outcome was circuit clotting. Eligible designs included RCTs, cohort, pilot, and relevant animal studies. References were screened in EndNote, with duplicates removed. Quality was assessed using the Newcastle–Ottawa Scale for clinical studies and SYRCLE’s Risk of Bias tool for animal studies. Results: Four studies were included: three clinical and one preclinical. The addition of nitric oxide (NO) to the sweep gas in the ECMO circuit was associated with fewer clotting events, fewer circuit changes, and reduced use of fresh frozen plasma (FFP). Red blood cell and platelet transfusion requirements did not differ significantly between the NO-treated patients and the control group. Methaemoglobin levels were slightly elevated in the NO group but remained within safe clinical limits. Conclusion: NO may improve ECMO circuit performance and reduce clotting without increasing bleeding risk. However, existing studies are limited by small sample sizes and a lack of randomised controlled trials. Further high-quality trials are needed to confirm its clinical benefit.