2002 Abstracts

BACKGROUND: The timing of aerosol generation during a breath and particle size both impact drug delivery during controlled mechanical ventilation (CMV).

Methods: Five Aeroneb^® Professional Nebulizers were modified to generate aerosols ranging from 3.4 to 5.4 mm volume median diameter (VMD), as determined by laser diffraction (Spraytecª, Malvern). To determine the effect of this variable with a small dose of 0.5 mL, albuterol sulfate (0.5% solution) was aerosolized continuously and during a portion of inspiration (optimized phasic). The nebulizer was operated in the humidified inspiratory limb of a Puritan Bennett 760 Ventilator (tidal volume 500 mL, peak flow 40 L/min, ramp flow pattern, I:E ratio 1:3, rate 15/min) attached to an intubated adult lung model. The amount of drug deposited on an absolute filter distal to an 8 mm ID endotracheal tube was determined for each aerosol particle size and generation pattern (n=3). Drug was eluted from the filter and determined by reverse phase HPLC with isocratic elution and UV detection at 275 nm.

Results: The percent of total dose ± standard deviation (SD) delivered to the test lung for each VMD and aerosol generation pattern tested is shown below.

SUMMARY: Optimized phasic aerosol generation yielded greater drug delivery for each particle size (p<0.01, ANOVA).

An inverse correlation (p<0.05, least squares analysis) was observed between deposition of drug and aerosol particle size across the range of particle sizes tested with both aerosol generation modes.

CONCLUSION: A combination of optimized phasic aerosol generation and smaller aerosol particles resulted in the most efficient drug delivery in vitro when using the modified Aeroneb Pro during CMV.