Can high efficiency aerosol delivery continue after extubation?

Background

Aerogen is currently developing drug/device combinations for delivery of drug to the lungs of mechanically ventilated patients with efficiencies above 60%. When therapy needs to continue post extubation, an aerosol delivery device of similar efficiency is required to deliver the same drug dose. Commercially available nebulizers with inhaled mass ranging from 6 to 30% would require several doses to achieve the same inhaled mass. We modified the pulmonary drug delivery system (PDDS; Aerogen) to provide similar drug delivery efficiencies to patients on and off the ventilator.

Methods

Three PDDS units were used to aerosolize albuterol sulfate (2.5 mg) to simulated patients in both on vent and off vent configurations (n = 3). On vent was simulated with a Puritan Bennett 740 Ventilator with tidal volume of 500 ml, peak flow 40 l/min, ramp flow pattern, I:E ratio 1:2, and rate of 15 breaths/min through an 8-mm endotracheal tube attached to a passive lung model (Ingmar). The off vent configuration consisted of an adult lung simulator (Hans Rudolph) with a tidal volume of 500 ml, peak flow 28 l/min, and I:E ratio 1:2. The amount of drug deposited on an absolute filter distal to the endotracheal tube and mouthpiece was eluted and determined by reverse-phase HPLC with isocratic elution and UV detection at 275 nm. The volume median diameter (VMD) and geometric standard deviation of the aerosol were determined by laser diffraction (Spraytech™ Malvern).

Results

The percentage of total dose ± standard deviation delivered to the test lung was 72 ± 11% on vent and 70 ± 0.3% off vent. The mean VMD was 3.5 μm with a GSD of 2.1.

Summary

Our in vitro results demonstrate that it is feasible to provide comparable high-efficiency aerosol delivery to adult patients whether on or off the ventilator. Additional studies with the PDDS in vivo will be required to establish the in vitro/in vivo correlations of this model.

Conclusion

The Aerogen PDDS delivered > 60% of the total dose to the airway of simulated adult patients during mechanical ventilation and spontaneous breathing.