Introduction: Extracorporeal membrane oxygenation (ECMO) has become a valuable modality for managing pediatric patients with cardiac and/or respiratory failure that is refractory to conventional intensive care strategies. However, it is associated with aberrations in coagulation due to systemic activation of the inflammatory cascade. Nitric oxide (NO), a well-known vasodilator and anti-inflammatory mediator with anti-platelet effects, has been investigated for improving perioperative outcomes when used in cardiopulmonary bypass, showing promise in improving postoperative platelet counts and preventing significant post-surgical bleeding. Recent literature has sought to expand its use in ECMO circuitry. This review aims to synthesize the available data examining the use of nitric oxide in sweep gas in pediatric ECMO, albeit limited, to spark further prospective analysis. Methods: Studies were identified through PubMed, and preclinical studies and retrospective studies were included, while case reports and letters were excluded. Titles and abstracts were reviewed for relevance, followed by full-text review of eligible articles. Results: Overall, NO represents a promising adjunct therapy on ECMO without added risk to the patient. Limited retrospective studies have demonstrated that the addition of NO to the ECMO oxygenator in pediatric patients resulted in fewer circuit changes and a lower associated risk of neurologic injury. When used in conjunction with therapeutic bivalirudin, NO was also associated with fewer fresh-frozen plasma transfusions, without clinically significant methemoglobinemia or differences in adverse bleeding events. In vitro and animal studies further support the potential benefits of NO, demonstrating higher platelet counts and lower beta-thromboglobulin levels, without an increase in methemoglobin levels. There is no clear dosing recommendation, and some suggest that high doses (> 40 ppm) may be necessary for efficacy. Conclusions: The available evidence suggests that the addition of NO to the sweep gas in pediatric ECMO plays a role in mitigating thrombosis and inflammation, without increasing the risk of bleeding or methemoglobinemia. However, multicenter prospective studies and/or randomized controlled trials are needed to establish safety, efficacy, and accurate treatment guidelines.
Menon et al. (Sun,) studied this question.