Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m–labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles <5.8 μm in diameter (NES-spacer = Babyhaler > Aerochamber-Infant;p < 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52–5.40% of the delivered dose) but greater with the NES-spacer than with the Aerochamber-Infant or the Babyhaler (5.40 ± 2.40%, 2.91 ± 0.86%, 0.52 ± 0.46%, respectively;p = 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants.