Aerosol delivery during invasive mechanical ventilation: a systematic review

Abstract

Background: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed.

Methods: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias.

Results: Twenty-six clinical and ten experimental studies were included. Between 30% and 43% of nominal drug dose was lost to the circuit in ventilated patients. Whole lung deposition of up to 16% and 38% of nominal dose (proportion of drug charged in the device) were reported with nebulizers and metered-dose inhalers, respectively. A penetration index inferior to 1 observed in scintigraphic studies indicated major proximal deposition. However, substantial concentrations of antibiotics were measured in the epithelial lining fluid (887 (406-12,819) μg/mL of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 μg/g of amikacin) dissected from infected piglets, suggesting a significant distal deposition. The administration technique varied among studies and may explain a degree of the variability of deposition that was observed.

Conclusions: Lung deposition was lower than 20% of nominal dose delivered with nebulizers and mostly occurred in proximal airways. Further studies are needed to link substantial concentrations of antibiotics in infected pulmonary fluids to pulmonary deposition. The administration technique with nebulizers should be improved in ventilated patients in order to ensure an efficient but safe, feasible and reproducible technique.

Keywords: Antibiotics; Bronchodilators; Nebulizer; Scintigraphy.

Fig. 1

Flow diagram for study selection according to Moher et al. [11] AT aerosol therapy, IMV invasive mechanical ventilation

Fig. 2

Anteroposterior acquisition using planar scintigraphy for radiolabeled aerosol deposition assessment in an intubated patient after open-heart surgery (from Thomas et al. [37], with permission) (a), a tracheotomised critically ill patient (from O’Riordan et al. [35], with permission) (b) and three intubated neurosurgical patients ventilated in volume control mode (from Dugernier et al. [18] with permission) (c). Even if lung outlines suggested that inhaled drugs reached the lung periphery, these images illustrate that the majority of drugs impacted proximally in the artificial airways and particularly in the trachea and large bronchi. High deposition in the endotracheal tube, the trachea and the main bronchi has been masked to improve lung definition (a)

Fig. 3

Extrapulmonary deposition expressed as percentage of nominal dose of nebulized drugs (Neb) during invasive mechanical ventilation. O’Riordan et al. [35] reported drug percentage trapped in the endotracheal tube during inspiration only (7% of nominal dose was exhaled particles trapped during expiration). This was not differentiated in other studies. *Drug deposition in the inspiratory limb only, the expiratory limb was not included. ^†Drug retention in the nebulizer reservoir, the T-piece and the Y-piece. ^‡Drug deposition in the endotracheal tube, the trachea and main bronchi