Abstract
Non-invasive delivery of nebulized surfactant has been a long-pursued goal in neonatology. Our aim was to evaluate the performance of an investigational vibrating-membrane nebulizer in a realistic non-invasive neonatal ventilation circuit with different configurations. Surfactant (aerosols were generated with a nebulizer in a set-up composed of a continuous positive airway pressure (CPAP) generator with a humidifier, a cast of the upper airway of a preterm infant (PrINT), and a breath simulator with a neonatal breathing pattern. The lung dose (LD), defined as the amount of surfactant collected in a filter placed at the distal end of the PrINT cast, was determined after placing the nebulizer at different locations of the circuit and using either infant nasal mask or nasal prongs as CPAP interfaces. The LD after delivering a range of nominal surfactant doses (100–600 mg/kg) was also investigated. Surfactant aerosol particle size distribution was determined by laser diffraction. Irrespective of the CPAP interface used, about 14% of the nominal dose (200 mg/kg) reached the LD filter. However, placing the nebulizer between the Y-piece and the CPAP interface significantly increased the LD compared with placing it 7 cm before the Y-piece, in the inspiratory limb. (14% ± 2.8 vs. 2.3% ± 0.8, nominal dose of 200 mg/kg). The customized eFlow Neos showed a constant aerosol generation rate and a mass median diameter of 2.7 μm after delivering high surfactant doses (600 mg/kg). The customized eFlow Neos nebulizer showed a constant performance even after nebulizing high doses of undiluted surfactant. Placing the nebulizer between the Y-piece and the CPAP interface achieves the highest LD under non-invasive ventilation conditions.
Highlights
The first attempts to deliver exogenous surfactant to preterm infants date back to 1964 and consisted of nebulizing synthetic DPPC microaerosols into the atmosphere of neonatal incubators [1]
A slightly higher amount of surfactant was detected in the backup trap using the nasal prongs, whereas a marginally significant higher amount of surfactant was detected in the expiratory filter using the nasal mask. These findings suggest that the geometry of the nasal mask may offer an extra little space for the aerosol cloud to expand, which slightly reduced the impaction of surfactant droplets within the interface, and promoted a greater surfactant loss during exhalation
The investigational vibrating-membrane nebuliser used in this study showed a consistent surfactant aerosol production rate and maintained the aerosol characteristics unchanged—even after having delivered high doses of undiluted Poractant alfa at a concentration of 80 mg/mL
Summary
The first attempts to deliver exogenous surfactant to preterm infants date back to 1964 and consisted of nebulizing synthetic DPPC microaerosols into the atmosphere of neonatal incubators [1]. These attempts were obviously unsuccessful and moved the field towards the development of intratracheal surfactant instillation protocols [2], which later gained clinical approval for the treatment of neonatal Respiratory Distress Syndrome (RDS). Surfactant replacement therapy remains a first-line treatment for RDS that improves survival and reduces the incidence of pneumothorax [3] It is considered an invasive therapy, often requiring positive pressure ventilation, which is considered as an important risk factor for developing Bronchopulmonary Dysplasia (BPD). An alternative method that consist in the use of a Laryngeal Mask Airway (LMA) seems appealing but is still under investigation [6]
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