Inhaled Nitric Oxide in Neonates with Pulmonary Hypertension in Amazonas, Brazil: Physiological Improvement Versus Impact on Relevant Clinical Outcomes

BackgroundInhaled nitric oxide (iNO) is a standard treatment for neonatal pulmonary hypertension in high-resource settings. Yet, its efficacy and cost-effectiveness in low- and middle-income countries (LMICs) remain underexplored. This study aimed to evaluate the impact of iNO on neonatal outcomes within a resource-limited Neonatal Intensive Care Unit (NICU) setting in Manaus, Brazil, to inform public health strategies. MethodsWe conducted a multicenter, quasi-experimental study employing a historical control design. We compared outcomes in 12 prospective neonates receiving iNO for persistent pulmonary hypertension of the newborn (PPHN) secondary to perinatal asphyxia (March-August 2018) with 12 historical controls (December 2015-December 2016). Participants were at a gestational age of more than 34 weeks with echocardiographic evidence of PPHN. Main outcomes included oxygenation parameters, mortality, and length of hospital stay. ResultsThe prospective group demonstrated significant acute improvement in all key oxygenation parameters following initiation of iNO (p < 0.01 for PO2, O2 saturation, PO2/FiO2, and Oxygenation Index). However, iNO did not significantly reduce overall mortality (16.6% vs. 0%, p = 0.48) or NICU length of stay (21.3 vs. 13.2 days, p = 0.09). Notably, total hospital length of stay was significantly longer in the iNO group (37.1 vs. 23.08 days, p=0.03), with deaths primarily linked to systemic complications. ConclusionAlthough iNO acutely improves oxygenation in neonates with PPHN in this resource-limited setting, these physiological benefits did not result in reduced mortality or shorter NICU stays and were associated with increased overall hospitalization. The findings indicate that iNO sustains critically ill neonates who subsequently require extended care. Effective implementation of costly interventions in LMICs requires a comprehensive supportive infrastructure. Further context-specific research is crucial for informing resource allocation and enhancing neonatal care.v