Bovine surfactant in the treatment of pneumonia-induced-neonatal acute respiratory distress syndrome (NARDS) in neonates beyond 34 weeks of gestation: a multicentre, randomized, assessor-blinded, placebo-controlled trial

Abstract

Neonatal acute respiratory distress syndrome (NARDS) reflects pulmonary surfactant dysfunction, and the usage of bovine surfactant (Calsurf) supplement may therefore be beneficial. To determine whether bovine surfactant given in NARDS can improve oxygenation and survival rate, we conducted a multicenter, randomized trial between January 2018 and June 2019, and we compared Calsurf treatment to controls in neonates with pneumonia accompanied by NARDS. Neonates who met the Montreux criteria definition of NARDS were included, and those with congenital heart and lung malformations were excluded. Primary outcomes were oxygenation index (OI) after Calsurf administration, and secondary outcomes were mortality, and duration of ventilator and oxygen between the two groups, and also other morbidities. Cumulatively, 328 neonates were recruited and analyzed, 162 in the control group, and 166 in the Calsurf group. The results shows that OI in the Calsurf group were significantly lower than that in the control group at 4 h (7.2 ± 2.7 and 11.4 ± 9.1, P = 0.001); similarly, OI in the Calsurf group were significantly lower than in the control group at 12 h ( 7.5 ± 3.1 and 11.2 ± 9.2, P = 0.001). Mortality and duration of ventilator support or oxygen use between the two groups were not significantly different.Conclusion: Calsurf acutely improved OI immediately after administration in pneumonia-induced NARDS; although, we observed no significant decrease in mortality, duration of ventilator or oxygen, or major morbidity. What is known: • The definition proposed as the Monteux criteria for neonatal acute respiratory distress syndrome (NARDS). • Surfactant acutely improved oxygenation and significantly decreased mortality in children and adolescents with acute lung injury. What is new: • This is the first large randomized controlled trail to study on surfactant treatment of neonates with acute respiratory distress syndromes. • Surfactant acutely improved oxygenation immediately after administration in pneumonia-induced NARDS at a gestational age beyond 34 weeks.

Keywords: Acute respiratory distress syndrome; Neonate; Oxygenation index.

Fig. 1

Flow chart of the participants

Fig. 2

Oxygen index in mild, moderate and severe NARDS. a mild NARDS; b moderate NARDS; c severe NARDS; d total. The overall p value for within patients comparisons: in Calsurf treatment group, OI decreased significantly after 4 h surfactant given (7.23 ± 2.73 at 4 h, 14.89 ± 11.44 at 0 h, P < 0.001) and 12 h given (7.53 ± 3.13 at 12 h, 14.89 ± 11.44 at 0 h, P < 0.001), while the same change pattern can be seen in control group, although the decline is not as obvious as control group. The between-group patients’ comparisons: Calsurf administration significantly decreased the OI in mild, moderate, and severe cases of NARDS, especially moderate and severe cases. Data shown are mean values; error bars indicate SEM. *P < 0.05for the significant difference between groups