Aerosolized Surfactant: What Is the Cost of Avoiding Intubation?

Abstract

We read, with great interest, the pragmatic multicenter trial on aerosolized surfactant presented by the Aero-O2 study investigators.1 This is the largest clinical trial evaluating the efficacy of aerosolized surfactant for preterm infants with respiratory distress syndrome (RDS) and adds to the recent data reported by CureNeb study team.2 We would like to congratulate the investigators for introducing a novel technique of delivering aerosolized surfactant using an interface resembling a pacifier. This ensures continuous aerosol delivery without loss of positive end-expiratory pressure. However, we would like to highlight a few issues and request clarifications regarding the trial.The infants enrolled in the study had a mean gestational age of 33 weeks and mean birth weight of ∼2.1 kg. The number of infants born at ≤26 weeks’ gestation was small (n = 11). The proportion of infants requiring intubation for surfactant instillation was 26% in the aerosolized surfactant group and 50% in the usual care group. However, the requirement for surfactant reported in the current study is much higher than what is described in literature. Using data from a large prospective cohort study, including 18 tertiary NICUs, researchers reported that only 12.8% of infants born at 33 weeks’ gestation require surfactant.3 Also, in the present trial, infants in the intervention group received higher surfactant doses (6 mL/kg) and, sometimes, multiple treatments (up to 3 doses).The primary outcome of the study was the need for intubation and instillation of liquid surfactant. However, the oxygen requirement or respiratory distress score was not documented. The decision to ventilate a preterm infant is highly subjective and can vary from center to center. Although this approach contributes to the pragmatic design of the trial, it decreases its generalizability.The authors have demonstrated the safety and feasibility of using this novel aerosol technique in multiple NICUs. However, the cost implications of using higher and multiple surfactant dosage has not been reported. We would like the investigators to explore and report the cost-effectiveness of this potentially beneficial noninvasive therapy. Providing a treatment modality with a significantly higher cost for an intervention not showing any reduction in relevant outcomes, like chronic lung disease (CLD) or mortality, limits its applicability outside of the research settings. In this trial, aerosolized surfactant did not seem to reduce the need for intubation and surfactant administration in extremely preterm infants. In future trials, researchers could test this treatment approach in smaller infants (≤28 weeks) and report if aerosolized surfactant has the potential to reduce CLD in this challenging population.