Revisiting Inhaled Nitric Oxide Utilization in Congenital Diaphragmatic Hernia: A National Cohort Study of Major Children's Hospitals in the United States.

PURPOSE: For over a decade, there has been evidence suggesting a lack of efficacy of inhaled nitric oxide (iNO) in the treatment of pulmonary hypertension associated with congenital diaphragmatic hernia (CDH). Our study aimed to evaluate hospital-level data on contemporary iNO use in CDH infants.

METHODS

The Pediatric Health Information System database was queried for neonates with CDH managed at 48 major children's hospitals in the United States (2016-2023). Hospitals were stratified into high-use (>75th percentile) and low-use (<25th percentile) iNO hospitals. The primary outcome was in-hospital mortality, and secondary outcomes were extracorporeal membrane oxygenation (ECMO) use, mechanical ventilation duration, hospital length of stay, and hospital charges.

RESULTS

Among 2565 CDH neonates, iNO use decreased over the study period from 51.4 % to 42.9 % (p = 0.03). iNO utilization ranged from 24 % to 100 % across hospitals. High-use hospitals had significantly higher mortality rates compared to low-use hospitals (19.9 % vs. 12.4 %, respectively; p = 0.0003). ECMO cannulation rates (p = 0.34) and duration (p = 0.61) were similar between high- and low-use hospitals. High-use hospitals had increased mechanical ventilation duration, longer length of stay, and increased hospital charges compared to low-use hospitals (all p < 0.0001). The median iNO charge was $4338 [IQR $1529-$8330] per day.

CONCLUSION

Use of iNO in CDH neonates is declining but continues to vary widely among major children's hospitals. Given the high cost and unclear efficacy of iNO on CDH outcomes, these data represent a call for more prospective trials to develop evidence-based guidelines to help manage pulmonary hypertension in this challenging patient population.

LEVEL OF EVIDENCE: Level III.