Comparison of Inhaled Epoprostenol and Inhaled Nitric Oxide for COVID-19 Induced ARDS in Critically Ill Adults: A Multicenter Observational Study

Objectives To compare the clinical impact of inhaled epoprostenol (iEPO) and inhaled nitric oxide (iNO) in mechanically ventilated patients with COVID-19 induced acute respiratory distress syndrome (ARDS). The primary outcome was the difference in the maximum change in PaO2:FiO2 during the initial 24 hours after study group initiation between iEPO and iNO. Secondary outcomes included differences in inpatient mortality and hospital length of stay. Design Multicenter, observational cohort study. Setting Eleven hospitals in Arizona, Colorado, and Wyoming. Patients Adult patients with a documented diagnosis of COVID-19 admitted between January 2020 and January 2022 who received continuous administration of inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) and moderate to severe ARDS, defined as a partial pressure of oxygen to fraction of inspired oxygen (PaO2:FiO2) ratio of < 150 mmHg. Interventions None Measurements and Main Results A total of 200 patients were enrolled in the study with equal distribution of patients in the iEPO and iNO groups. The maximum change in PaO2:FiO2 ratio within 24 hours from baseline in the iEPO and iNO groups was 40.7 ± 57.1 and 62.7 ± 74.0 mmHg, respectively (p = 0.0194). Inpatient mortality was higher in the iEPO group compared to the iNO group (91% vs 72%, p = 0.001). The mean length of stay was longer in the iNO group compared to the iEPO group (28.3 days vs 18 days, p = 0.0002). Multivariate logistic regression analysis revealed that variables associated with increased mortality included use of iEPO (OR, 0.25; 95% CI, 0.113 to 0.645), norepinephrine dose (OR, 1.05; 95% CI, 1.004 to 1.090), and use of extracorporeal membrane oxygenation (OR, 0.133, 95% CI, 0.028 to 0.636). Conclusions In patients with moderate to severe COVID-19 induced ARDS, use of iNO was associated with greater improvements in PaO2:FiO2 ratio and lower inpatient mortality.