Clinical efficacy of early repeated endotracheal pulmo-nary surfactant combined with inhaled nitric oxide in the treatment of persistent pulmonary hypertension of the newborn

HU Xiao-long; ZHANG Xiao-hua; JIN Li-zhu

doi:10.3969/j.issn.1009-8933.2025.2.lnxxgbzz-e202502005

Abstract：Background: Persistent pulmonary hypertension (PPHN) of the newborn is one of the major contributors to neonatal mortality. Current conventional treatments for PPHN primarily encompass mechanical ventilation, inhaled nitric oxide (iNO), sildenafil, and magnesium sulfate. In confirmed cases of neonatal respiratory distress syndrome, pulmonary surfactant (PS) can be considered as a potential treatment option; however, the optimal dosage and administration frequency of PS remain subjects of ongoing debate. This study aimed to assess the efficacy of early repeated endotracheal PS administration combined with iNO therapy in the management of newborns with PPHN. Methods: Twenty-three neonates with PPHN received iNO alongside foundational treatments, including anti-infection therapy, mechanical ventilation, acidosis correction, and blood pressure stabilization. The observation group (n=13) received endotracheal instillation of PS three times, with each administration spaced six hours apart; the control group (n=10) received endotracheal instillation of PS once. Parameters compared included blood gas indices, oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (PA-aDO2), pulmonary artery systolic pressure (PAP), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Mechanical ventilation duration, oxygen therapy time, hospitalization length, and survival outcomes were recorded and compared between groups. Results: The blood gas parameters, OI, and PA-aDO2 showed no significant differences between the two groups of children before treatment (P>0.05). By 24-hour post-treatment, both groups exhibited significant increases in partial pressure of oxygen (PaO2) and potential of hydrogen (PH) levels, alongside significant decreases in lactate, partial pressure of carbon dioxide (PaCO2), OI, and PA-aDO2, with statistically significant differences (P<0.05). By 48-hour post-treatment, the observation group demonstrated significantly better improvements in blood gas parameters, OI, and PA-aDO2 compared to the control group, and these differences were statistically significant (P<0.05). There was no statistically significant difference in PAP and NT-pro-BNP levels between the two groups before treatment (P>0.05). After treatment, both groups showed significant decreases in PAP and NT-pro-BNP levels (P<0.05), with a more pronounced reduction observed in the observation group (P<0.05). The observation group had significantly shorter durations of mechanical ventilation and oxygen therapy compared to the control group, with statistically significant differences (P<0.05). Additionally, the observation group exhibited a shorter total hospital stay and a lower mortality rate than the control group, though these differences were not statistically significant (P>0.05). Conclusions: Early consecutive multiple doses of PS combined with iNO, compared to a single dose, better improves respiratory function indices, maintains stability, reduces pulmonary artery pressure, enhances cardiac function, shortens ventilator dependency, and increases cure rates in PPHN neonates. This approach is particularly suitable for severe PPHN cases, especially those with underlying pulmonary conditions.