Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome

Abstract

Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.

In Vitro Performance of an Investigational Vibrating-Membrane Nebulizer with Surfactant under Simulated, Non-Invasive Neonatal Ventilation Conditions: Influence of Continuous Positive Airway Pressure Interface and Nebulizer Positioning on the Lung Dose

“…Surfactant replacement therapy by nebulization during non-invasive ventilation represents a truly non-invasive surfactant administration method, which, unfortunately, remains an unfulfilled goal of modern neonatal care. Several clinical studies have demonstrated the safety of nebulized surfactant in combination with continuous positive pressure ventilation (CPAP) [7][8][9][10][11]. Recently, Minocchieri et al have demonstrated that Poractant alfa nebulized with a vibrating-membrane nebulizer reduces the need for intubation in 32 0 -33 6 weeks gestational age (GA) infants with mild RDS, although no differences were observed in 29 0 -31 6 weeks GA babies [11].…”

Aerosol delivery of synthetic lung surfactant

“…The combination of nCPAP and aerosolized surfactant has been explored in small pilot studies in premature infants with clinical (animal-derived) lung surfactants and first generation synthetic surfactants (Exosurf Neonatal ® and Surfaxin ® ) (Jorch et al, 1997 [Alveofact ® ]; Arroe et al, 1998 [Exosurf Neonatal ® ]; Berggren et al, 2000 [Curosurf ® ]; Finer et al, 2010 [Surfaxin ® ]), but these studies did not provide good data on clinical efficacy, aerosol generation and nCPAP, and particle size in lung deposition (Pillow & Minocchieri, 2012). As a result, a recent Cochrane Systematic Review concluded that there are insufficient data to support or refute the use of nebulized surfactant in clinical practice (Abdel-Latif & Osborn, 2012).…”

Novel Surfactant Administration Techniques: Will They Change Outcome?

“…For this method to be effective, aerosolized particles of surfactant ranging from 1 to 5 μm in diameter must be delivered to the lungs in a predictable and reproducible fashion. Many different surfactant preparations and nebulizers have been developed and tested in small trials [20, 21]. However, the optimal combination and dosages have yet to be determined.…”