A Compartment-Based Mathematical Model for Studying Convective Aerosol Transport in Newborns Receiving Nebulized Drugs during Noninvasive Respiratory Support

Abstract

Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (DDL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying DDL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient–ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on DDL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the DDL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures.

A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome

“…The difference in lung deposition may be explained by the fact that preclinical studies were conducted using tightly sealed neonatal ventilation circuits to minimize the air leaks around the nCPAP interface, which are common in clinical practice and might have contributed to a significant surfactant aerosol loss in the present study. A recent mathematical modelling study investigating the convective aerosol transport during neonatal NRS estimated that up to 70% of the aerosol delivered by the nebulizer could be lost due to leaks at the patient interface [26]. In vitro studies also highlighted that the size and geometry of different commercially available nasal prongs influenced the aerosol delivery and significantly affected the lung dose [27].…”

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

“…Nevertheless, these assumptions are not necessarily true in case of NIV in neonates since leakages are common and, generally, the inner volume of the nebulizer often approaches the tidal volume of the infant. Tarantini et al have recently developed a compartment-based mathematical model that allows estimating the impact of air leaks and nebulizer volume on the lung dose during NIV in premature neonates [104]. For instance, air leaks reduce the amount of drug delivered to the patient, which is released in the environment, whereas the internal volume of the nebulizer may act as a drug reservoir if the tidal volume of the infant is lower than the volume of the nebulizer.…”