International journal of pharmaceutics · 2026
Influence of inspiratory flow and inspiratory-to-expiratory ratio on aerosol deposition during controlled mechanical ventilation using different nebulizer technologies.
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Leclerc Lara, Bonsignore Jordan, Montigaud Yoann, Odouard Emmanuel, Pourchez Jérémie, Rejeaunier Arthur, Prévôt Nathalie, Périnel Sophie
Аннотация
Aerosol delivery during invasive mechanical ventilation is influenced by multiple factors, including nebulizer type and ventilatory settings. Current intensive care unit (ICU) guidelines generally provide limited recommendations regarding modification of ventilatory parameters during aerosol administration because available evidence remains heterogeneous. However, most available data originate from simplified in vitro models or evaluate individual components of aerosol delivery, limiting understanding of how aerosol characteristics interact with respiratory mechanics under realistic ventilatory conditions. This study evaluated how inspiratory flow and inspiratory-to-expiratory (I:E) ratio influence aerosol transport and respiratory tract deposition according to nebulizer technology using a controlled preclinical model. The objective was not to establish superiority between commercial devices, but to determine whether ventilatory parameters differently modulate aerosol fate depending on aerosol generation technologies. Using a validated ex vivo porcine respiratory model under volume-controlled ventilation, we assessed the impact of inspiratory flow (35 vs. 60 L/min) and I:E ratio (1:2 vs. 1:3) on respiratory tract deposition. Experiments were performed with a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN) placed 15 cm upstream of the Y-piece, with active heated humidification. Deposition was measured by planar scintigraphy with radiolabeled aerosol and a mass balance approach. VMN showed significantly higher delivery efficiency than JN in all conditions. With VMN, lower inspiratory flow increased respiratory tract deposition (57% ± 8% vs. 45% ± 5%, p = 0.022), and a longer expiratory phase (I:E 1:3 vs. 1:2) further improved deposition (60% ± 9% vs. 45% ± 5%, p < 0.0001), with reduced losses in the inspiratory limb. In contrast, JN had low output and no significant variation across settings. Ventilatory parameters significantly influence aerosol deposition with VMN but not JN in mechanical ventilation. Combining lower inspiratory flow and prolonged expiratory time increased respiratory tract deposition with VMN under the investigated experimental conditions. Further studies are required to determine whether these findings translate into clinical benefit.