The Controversy Persists: Is There a Qualification Criterion to Utilize Inhaled Nitric Oxide in Pre-term Newborns?

Abstract

Inhaled nitric oxide (iNO) use in premature newborns remains controversial among clinicians. In 2014, the American Academy of Pediatrics, Committee on Fetus and Newborn released a statement that the available data do not support routine iNO use in pre-term newborns. Despite the absence of significant benefits, 2016 California data showed that clinicians continue to utilize iNO in pre-term infants. With studies as recent as January 2017, the Cochrane review confirmed no major advantages of iNO in pre-term newborns. Still, it recognized that a subset of pre-term infants with pulmonary hypertension (PHTN) had not been separately investigated. Furthermore, recent non-randomized controlled trials have suggested that iNO may benefit specific subgroups of pre-term newborns, especially those with PHTN, prolonged rupture of membranes, and antenatal steroid exposure. Those pre-term infants who showed a clinical response to iNO had increased survival without disability. These findings underscore the need for future studies in pre-term newborns with hypoxemic respiratory failure and PHTN. This review will discuss the rationale for using iNO, controversies regarding the diagnosis of PHTN, and additional novel approaches of iNO treatment in perinatal asphyxia and neonatal resuscitation in the pre-term population < 34 weeks gestation.

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

“…Moreover, higher doses do not provide any additional advantages. The absolute contra-indication of iNO is methemoglobinemia (36,37).…”

Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

“…Although inhaled NO has been successfully tested in neonates and adult patients with acute respiratory distress syndrome (Feng et al, 2021;Lotz et al, 2021;Safaee Fakhr et al, 2021), the clinical benefit of intrapulmonary administration is still subject to much debate (Sokol et al, 2016;Vieira et al, 2021). In this line, the oxygenation of the tissues is a main factor when the rather controversial results of gasotransmitter reactions are discussed.…”

Management Practices During Perinatal Respiratory Transition of Very Premature Infants

“…In our practice, iNO treatment is not attempted when an extremely immature infant (21–23 weeks of gestation) fails to respond to resuscitation. On the other hand, according to therapeutic trials, iNOS treatment has no significant beneficial effects to VLGA infants with uncomplicated respiratory distress ( 120 , 130 ). The controversy on the indications and potential beneficial effects of iNO will likely continue.…”

“…According to meta-analysis, no increase in survival without BPD was observed, with an apparent exception of infants with African-American background. According to cohort studies, most patients with iNO treatment of early PPHN have survived, whereas the untreated historical controls almost exclusively died ( 118 , 130 ).…”