Does nebulised surfactant benefit neonates with respiratory distress syndrome on noninvasive respiratory support?

Nasal continuous positive airway pressure (CPAP) is the primary mode of respiratory support in the preterm neonates with respiratory distress syndrome (RDS). In comparison with intubation, use of nCPAP is associated with reduced need of surfactant administration, intubation and bronchopulmonary dysplasia in extremely preterm neonates (1,2). Furthermore, prophylactic surfactant administration has not been found to be superior to early selective surfactant administration if nCPAP fails (3). If surfactant administration is needed, administration by minimally invasive technique (MIST) using a thin catheter while baby is supported with nCPAP may be associated with better respiratory outcomes when compared to administration via an endotracheal tube, as in the INSURE approach (4). With this background, the study reviewed here evaluates the role of a noninvasive approach of surfactant administration – by aerosolisation. This randomised controlled trial recruited moderately and very preterm neonates with mild RDS who needed FiO2 of less than 30% to maintain normoxia when supported by nCPAP (5). Neonates in the intervention group received aerosolised surfactant while neonates in the control group received sham nebulisation. The primary outcome of need of intubation was significantly reduced in the intervention group. Duration of ventilation and incidence of air leaks were similar in the two groups. This study presents an attractive noninvasive method of surfactant administration which can also potentially improve the ease of administration. The study had higher than expected rates of intubation and surfactant use in both 29–31 weeks and 32–33 weeks of gestation study subgroups. This may be due to lower threshold of surfactant administration not only as defined in the study protocol but also on discretion of the clinical team. As a result, the reduced need of intubation in the intervention group observed in this study may not be applicable to other healthcare settings which follow a selective surfactant administration strategy. An important limitation of study is low rate of recruitment due to nonavailability of study personnel (17.7% of eligible neonates recruited) which also led to early stopping of the study. Although the effect size of the study intervention reaches significance, the confidence interval is wide with upper margin of relative risk nearing the point of no effect. Furthermore, the numbers presented for the primary outcome vary when presented at different places throughout the manuscript (Table 1, see full review on the EBNEO website). It is clear that even a small change in numbers can alter the effect size and its confidence interval for such a small study. Minimally invasive technique without need of endotracheal intubation is an attractive proposition. Of many methods of minimally invasive surfactant administration (including thin catheter, laryngeal mask airway and pharyngeal deposition), the aerosolised administration is least invasive. However, many questions including dose, timing and frequency of administration, method of aerosolisation and target patient group most likely to be benefitted remain unanswered. Further research is warranted in investigating the use of different methods of minimally invasive or noninvasive methods of surfactant therapy. Such a research should be conducted in neonates in whom surfactant therapy is warranted as a standard practice. URL TO THE FULL REVIEW ON THE EBNEO WEB SITE https://ebneo.org/2019/01/nebulized-surfactant/