Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors

We attempted to resolve the discrepancies in reported data on aerosol depos ition from a chlorofluorocarbon (CFC)-propelled metered-dose inhaler (MDI) during mechanical ventilation, obtained by in vivo and in vitro methodologi es. Albuterol delivery to the lower respiratory tract was decreased in a hu midified versus a dry circuit (16.2 versus 30.4%, respectively; p < 0.01). In 10 mechanically ventilated patients, 4.8% of the nominal dose was exhale d. When the exhaled aerosol was subtracted from the in vitro delivery of 16 .2% achieved in a humidified ventilator circuit, the resulting value (16.2 - 4.8 = 11.4%) was similar to in vivo estimates of aerosol deposition. Havi ng reconciled in vitro with in vivo findings, we then evaluated factors inf luencing aerosol delivery. A lower inspiratory flow rate (40 versus 80 L/mi n; p < 0.001), a longer duty cycle (0.50 versus 0.25; p < 0.04), and a shor ter interval between successive MDI actuations (15 versus 60 s; p < 0.02) i ncreased aerosol delivery, whereas use of a hydrofluoroalkane (HFA)-propell ed MDI decreased aerosol delivery compared with the CFC-propelled MDI. A MD I and actuator combination other than that designed by the manufacturer alt ered aerosol particle size and decreased drug delivery. In conclusion, aero sol delivery in an in vitro model accurately reflects in vivo delivery, pro viding a means for investigating methods to improve the efficiency of aeros ol therapy during mechanical ventilation.