Aerosol Delivery During Mechanical Ventilation: A Predictive In-Vitro Lung Model

Abstract

Objective: to compare aerosol delivery from a standard (Bennett) nebulizer, a submicronic (Ultravent) nebulizer, a metered dose inhaler (MDI) plus small holding chamber, and an MDI plus large holding chamber, using a laboratory model simulating a mechanically ventilated patient. Method: saline solution (for the nebulizers) and fenoterol MDI's were radiolabelled and the model set up. After 15 minutes nebulization, or after single puffs from MDI, 1 minute static images were taken of the filter (representing the lungs'). Radioactivity in the filter was then counted and expressed as a percentage of the initial radioactivity in the nebulizer, or per puff from MDI. Counts were also made of the endotracheal tube (ETT) and chamber in a subgroup of studies. Results: radioactivity delivered to the filter from MDI plus large chamber (30.3 ± 7.4%) (mean ± 1 SD) and MDI plus small chamber (27.7 ± 5.1%) was significantly greater than from Bennett (4.6 ± 2.1%) and Ultravent (1.3 ± 0.4%) nebulizers. In experiments using MDI plus small chamber there was 52.1 ± 5.8% deposition into the chamber, and 5.9 ± 2.0% deposition onto the ETT. In experiments using Bennett nebulizer there was 2.3 ± 1.0% deposition to the ETT. Comparison of 'lung' inhalation from Bennett nebulizer between experiments with and without humidity was 4.6 ± 2.1% and 7.8 ± 0.5% respectively (p = 0.002). Conclusions: 1) Delivery of aerosol to the model lung is greater using MDI plus chamber than using nebulizer. 2) There is no significant difference in activity delivered to the filter between MDI using either size of chamber.3) Much of the initial aerosol remains in the nebulizer or chamber, and less in the ETT. 5) Warming and humidification of the inspired gas reduces the amount of available aerosol towards the level of lung deposition seen in clinical studies. 4) Deposition to filter of both "Technetium sulphur colloid (99nTc-SC) and "Technetium pertechnetate (99Tc04) from a nebulized saline solution was reduced by approximately 50% when fenoterol was added to the solution. As this difference was similar for both KEY WORDS: aerosol, metered dose inhaler, bronchodllator, nebulizer, lung deposition, lung model 251 compounds, proportional differences of deposition between the devices tested here remain unchanged. 6) Lung models such as the one described in this study receive approximately 3 times as much on the filter as deposits in the lungs in human studies, for all devices. This is likely due in part to impaction of all the aerosol on the absolute filter in the model, but exhalation of part of the inhaled aerosol in human studies. 7) Further efforts must be made to develop models that more closely mimic human physiology in mechanically ventilated patients.

Pressurized Metered-Dose Inhalers Versus Nebulizers in the Treatment of Mechanically Ventilated Subjects With Artificial Airways: An In Vitro Study

“…[7][8][9][10]12,[13][14][15][16]23 This is consistent with the dose efficiency we obtained with each device and airway used in this study, which ranged from 3 to 15%. Aerosol was generated by a pMDI and jet nebulizer placed proximal to the airway in the inspiratory limb of a heated humidified ventilator circuit attached to the artificial airway placed orally or tracheally in an adult teaching mannikin.…”

“…Because the primary focus of previous research on aerosol delivery during mechanical ventilation was the ETT, [6][7][8][9][10][11][12][13][14][15][16] there are limited data in the literature on the delivery of inhaled medications administered with different aerosol devices in mechanically ventilated patients with TTs. Consequently, the difference between TTs and ETTs in drug delivery to ventilator-dependent patients is not clear, and determining the most efficient aerosol device for critically ill patients with a tracheostomy is essential to optimize effectiveness of drug delivery to this patient population.…”

Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients

“…Several in vitro model studies of a MDI and spacer revealed about 30% delivery to the lower respiratory tract [19,21,22]. These values are consistently higher than pulmonary deposition estimated by in vivo gammascintigraphic studies.…”

“…Various models of the ventilator circuit have been employed to assess in vitro aerosol deposition (table 1). In most studies, aerosol was collected distal to the endotracheal tube [13,16,17,22,23]. Subsequently, NIVEN et al [20] used a plastic syringe barrel with a simulated carina to quantitate aerosol deposition in the lower trachea.…”

Aerosol Therapy in Pulmonary Critical Care

“…Later, Fuller et al 29 confirmed that the efficiency of aerosol delivery with both pMDIs and nebulizers was lower in ventilator-dependent subjects than in ambulatory subjects. However, the delivery efficiency of aerosol devices in critical care has significantly improved over the years due to greater understanding of the scientific basis of aerosol therapy in 14,18,19,32,34,[38][39][40][41][42] There are significant differences in the delivery efficiency of aerosol devices due to many factors, which can be divided into 6 categories: (1) effect of particle size, (2) effect of drug formulations, (3) factors affecting aerosol device performance, (4) factors affecting aerosol drug delivery to ventilator-dependent patients, (5) factors affecting aerosol delivery to spontaneously breathing patients with artificial airways, and (6) effect of disease state and severity.…”