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Background: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery., Methods: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy., Results: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0-24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001)., Conclusion: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings., (© 2023. The Author(s).)

Background: Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction. Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed. The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation, with two modes: pressure support ventilation and volume-controlled ventilation., Methods: Seventeen postoperative neurosurgery patients without pulmonary disease were randomly ventilated in pressure support or volume-controlled ventilation. Diethylenetriaminepentaacetic acid labeled with technetium-99m (2 mCi/3 mL) was administrated using a vibrating-mesh nebulizer (Aerogen Solo(®), provided by Aerogen Ltd, Galway, Ireland) connected to the endotracheal tube. Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy., Results: Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation, respectively (p < 0.05). Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation (27.4 ± 6.6 vs. 20.7 ± 6.0 %, p < 0.05). A similar penetration index was observed for the right (p = 0.210) and the left lung (p = 0.211) with both ventilation modes. A high intersubject variability of lung deposition was observed with both modes regarding lung doses, aerosol penetration and distribution between the right and the left lung., Conclusions: In the specific conditions of the study, volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation. The clinical benefit of this effect warrants further studies. Clinical trial registration NCT01879488.