ABSTRACT
OBJECTIVE: To evaluate the real-world safety and effectiveness of inhaled nitric oxide (INOflo® for Inhalation 800 ppm) for perioperative pulmonary hypertension associated with cardiac surgery in Japan. METHODS: This was a prospective, non-interventional, all-case, post-marketing study of pediatric and adult patients who received perioperative INOflo with cardiac surgery from November 2015-December 2020. Safety and effectiveness were monitored from INOflo initiation to 48 h after treatment completion or withdrawal. Safety outcomes included adverse drug reactions, blood methemoglobin concentrations, and inspired nitrogen dioxide concentrations over time. Effectiveness outcomes included changes in central venous pressure among pediatrics, mean pulmonary arterial pressure among adults, and the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) in both populations. RESULTS: The safety analysis population included 2,817 Japanese patients registered from 253 clinical sites (pediatrics, n = 1375; adults, n = 1442). INOflo was generally well tolerated; 15 and 20 adverse drug reactions were reported in 14 pediatrics (1.0%) and 18 adults (1.2%), respectively. No clinically significant elevations in blood methemoglobin and inspired nitrogen dioxide concentrations were observed. INOflo treatment was associated with significant reductions in both central venous pressure among pediatrics and mean pulmonary arterial pressure among adults, and significant improvements in PaO2/FiO2 among pediatrics and adults with PaO2/FiO2 ≤ 200 at baseline. CONCLUSIONS: Perioperative INOflo treatment was a safe and effective strategy to improve hemodynamics and oxygenation in patients with pulmonary hypertension during cardiac surgery. These data support the use of INOflo for this indication in Japanese clinical practice.
