Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia

Pediatr Res. 2023 Jun;93(7):1899-1906. doi: 10.1038/s41390-023-02491-8. Epub 2023 Feb 1.

Abstract

Background: Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited.

Methods: This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses.

Results: Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05-4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11-5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use.

Conclusions: Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration.

Impact: Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited. The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use. Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use. Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.

Publication types

  • Multicenter Study

MeSH terms

  • Administration, Inhalation
  • Autonomic Nervous System Diseases*
  • Cohort Studies
  • Hernias, Diaphragmatic, Congenital* / complications
  • Humans
  • Hypertension, Pulmonary* / complications
  • Hypertension, Pulmonary* / drug therapy
  • Infant
  • Nitric Oxide
  • Retrospective Studies

Substances

  • Nitric Oxide