A. Sescleifer1, C. Chidiac1, Z. Hellman2, D. Solomon2, S. Kunisaki1 1Johns Hopkins University School Of Medicine, Pediatric Surgery, Baltimore, MD, USA 2Yale University School Of Medicine, Pediatric Surgery, New Haven, CT, USA
Introduction: Inhaled nitric oxide (iNO) is a pulmonary vasodilator commonly used to treat severe pulmonary arterial hypertension in infants with congenital diaphragmatic hernia (CDH). However, the therapeutic benefit of iNO in CDH remains controversial, with prior publications suggesting higher mortality with iNO use. In this study, we employed a national pediatric database to evaluate contemporary trends in iNO in CDH and to determine its association with resource utilization and mortality.
Methods: In this IRB-exempt study, the Pediatric Health Information System (PHIS) database was queried for infants with a diagnosis of CDH at 47 major children’s hospitals (2016-2023). Normally distributed data were reported as mean +/- standard deviation, and non-normally distributed data reported as median [interquartile range]. Data was analyzed with students t-test and chi-squared tests. Analyses were conducted using RStudio v4.2.2.
Results: Of 4886 CDH infants identified, 487 (10.0%) received iNO during their index hospital admission. Use of iNO by institution was highly variable, with 42.6% of children’s hospitals not using iNO in any patients over the course of the study period, and the remainder of institutions utilizing iNO only in select patients (range 1% to 61%). Rates of iNO utilization did not change over the study period (p=0.18). Female patients were significantly more likely to receive iNO compared to their male counterparts (female: 11.3% versus male: 9.0%, p=0.008). There was no significant difference in iNO use by birthweight (iNO: 2851 +/- 705 grams versus non-iNO: 2867 +/- 738 grams, p=0.64), gestational age (iNO: 38 weeks [IQR 35-39] versus non-iNO: 38 weeks [IQR 36-39], p=0.14), or race (p=0.07). iNO was more likely to be used in patients undergoing open cardiac repair (cardiac repair: 13.1% versus no cardiac repair: 8.7%, p=0.06); however, medically managed congenital heart disease (CHD) was not predictive of iNO use (CHD: 10.1% versus non-CHD: 9.0%, p=0.64). Rates of ECMO utilization were not different at institutions using iNO (p>0.9999), although patients requiring ECMO support were significantly more likely to receive iNO (ECMO: 43.1% versus non-ECMO: 21.1%, p<0.0001) and require a longer duration of ECMO support (iNO: 14 days [IQR 10-21] versus non-iNO: 12 days [IQR 7-20], p=0.19). iNO patients had a longer NICU length of stay (iNO: 50.5 days [IQR 22-96.25] versus non-iNO: 30 days [IQR 13-68], p<0.0001). Overall, mortality was significantly higher in patients receiving iNO (iNO: 27.1% versus non-iNO: 18.8%, p<0.0001) (Figure).
Conclusion: Over the study period, 57.4% of hospitals used iNO in the management of CDH, with rates of iNO utilization remaining stable over the past decade. Patients receiving iNO had higher resource utilization, with more frequent and longer duration of ECMO, prolonged NICU length of stay, and higher mortality. Further study of the utility of iNO in the management of CDH is warranted.