Clinical Status of Inhaled Nitric Oxide Treatment in Infants with Persistent Pulmonary Hypertension of the Newborn in Korea: Post-Marketing Surveillance Results

Abstract

Purpose: Inhaled nitric oxide (iNO) is a potent selective pulmonary vasodilator and an important treatment for newborn infants with hypoxic respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN). The Ministry of Food and Drug Safety of Korea first approved iNO in 2009 for use as a new drug to treat hypoxic respiratory failure with PPHN. A post-marketing surveillance study (PMSS) was conducted to assess the effectiveness and safety of the iNO treatment. We evaluated the clinical status of the iNO treatment currently available in Korea by using the PMSS data. Methods: We retrospectively reviewed the PMSS data from 22 hospitals in Korea from October 2014 to September 2018. Altogether, 97 infants were enrolled and divided into early response (ER), delayed response (DR), no response (NR), and death groups according to their response to the iNO treatment. Results: The ER group included 52 infants (53.6%); DR group, 33 (34.0%); NR group, seven (7.2%); and death group, five (5.2%). The iNO treatment was initiated within 14 days after birth at a concentration of 20 ppm. The median treatment duration was 91.5 hours (69.0 to 134.3) in all the infants. Of the infants, 43 (44.3%) received the treatment for >96 hours. Fifty-one infants (52.6%) needed >20 ppm of iNO, and 10 (10.5%) needed a maximum of 80 ppm of iNO. None of the infants had hypermethemoglobinemia or an alarm report of NO2. Conclusion: Korean neonatologists reported that a large proportion of the infants with PPHN showed improvement in oxygenation after treatment with the approved iNO. These infants received relatively longer durations and higher concentrations of the iNO treatment than the current recommendations, without any side and adverse effect.