Abstract
Background: Aerosolized drug dose delivered to the lungs is affected by solution concentration and osmolality. Salinity of solution may alter aerosol particle size distribution as higher salinity may prompt aerosol aging during nebulization. The aim of this study was to evaluate aerosol delivery with various solution salinity via a jet nebulizer during mechanical ventilation.
Methods: A Drager V300 ventilator operated in volume control (500 mL, 12 breaths/min, PEEP 5 cm H2O, TI 1.0s) with heated humidification at 37°C was connected to an endotracheal tube (ETT, 7.5 mm), inline with a collecting filter connected to a lung model with compliance of 0.06 L/cm H2O and resistance of 15 cm H2O/L/s (Michigan Instrument). A small volume nebulizer was filled with a unit-dose of salbutamol (GlaxoSmithKline Corp.) and diluted with 2 mL of distilled water, 0.45% saline, or 0.9 % saline, placed at 15 cm from the Y piece in the inspiratory limb of the ventilator circuit. and the nebulizer was powered by external compressed oxygen at 8 L/min till 3 minutes after sputter. An Anderson Cascade impactor (Thermo Fisher Scientific Corp.) operated with a flow 28.3 L/min was used to determine particle size distribution, placed at outlet of the nebulizer and distal to the ETT. The collected drug was eluted from filter and impactor and analyzed by a spectrophotometer with wavelength 276 nm. Statistical analyses were performed with ANOVA with a significance level of P< 0.05.
Results: Inhaled drug doses distal to the ETT were 4.9±0.8% with distilled water, 4.9±0.5% with 0.45% saline, and 5.4±0.8％ with 0.9% saline, with no statistical difference (P = 0.452). The mass median diameter (MMAD) were 1.37±0.01 um distal to the ETT for all solutions (P =1), yet varied at outlet of the nebulizer (2.2±0.1 um with distilled water, 1.8±0.1 um with 0.45% saline, and 2.23±0.2 um with 0.9% saline; P = 0.026). Figure 1 below demonstrated the comparisons of particle size measured at outlet of the nebulizer and through the mechanical ventilation system.
Conclusions: Salinity of dilution solution impacted MMAD emitted from a small volume jet nebulizer but did not affect drug dose and particle size delivered distal to the ETT. The MMAD of aerosols distal to ETT during mechanical ventilation with active heated humidification reduced, possibly due to a rainout effect from the contours of the system.
Experimental apparatus set-up. A ventilator was connected to a test lung via an endotracheal tube with an inline collecting filter or Andersen Cascade Impactor. A jet nebulzier was placed at 15 cm from the Y-piece of the inspiratory limb.
Comparisons of particle size measured at outlet of the nebulizer and through the mechanical ventilation system
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