Gupta P, Richardson T, Hall M, Bertoch D, Hebbar KB, Fortenberry JD, Wetzel
RC. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. Crit Care Med. 2016 Oct;44(10):1901-9.

OBJECTIVES: To evaluate the effect of inhaled nitric oxide on outcomes in children with acute lung injury.

DESIGN: Retrospective study with a secondary data analysis of linked data from two national databases. Propensity score matching was performed to adjust for potential confounding variables between patients who received at least 24 hours of inhaled nitric oxide (inhaled nitric oxide group) and those who did not receive inhaled nitric oxide (no inhaled nitric oxide group).

SETTING: Linked data from Virtual Pediatric Systems (LLC) database and Pediatric Health Information System.

PATIENTS: Patients less than 18 years old receiving mechanical ventilation for acute lung injury at nine participating hospitals were included (2009-2014).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: A total of 20,106 patients from nine hospitals were included. Of these, 859 patients (4.3%) received inhaled nitric oxide for at least 24 hours during their hospital stay. Prior to matching, patients in the inhaled nitric oxide group were younger, with more comorbidities, greater severity of illness scores, higher prevalence of cardiopulmonary resuscitation, and greater resource utilization. Before matching, unadjusted outcomes, including mortality, were worse in the inhaled nitric oxide group (inhaled nitric oxide vs no inhaled nitric oxide; 25.7% vs 7.9%; p < 0.001; standardized mortality ratio, 2.6 [2.3-3.1] vs 1.1 [1.0-1.2]; p < 0.001). Propensity score matching of 521 patient pairs revealed no difference in mortality in the two groups (22.3% vs 20.2%; p = 0.40; standardized mortality ratio, 2.5 [2.1-3.0] vs 2.3 [1.9-2.8]; p = 0.53). However, the other outcomes such as ventilation free days (10.1 vs 13.6 d; p < 0.001), duration of mechanical ventilation (13.8 vs 10.1 d; p < 0.001), duration of ICU and hospital stay (15.5 vs 12.2 d; p < 0.001 and 28.0 vs 24.1 d; p < 0.001), and hospital costs ($150,569 vs $102,823; p < 0.001) were significantly worse in the inhaled nitric oxide group.

CONCLUSIONS: This large observational study demonstrated that inhaled nitric oxide administration in children with acute lung injury was not associated with improved mortality. Rather, it was associated with increased hospital utilization and hospital costs.