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

Abstract

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 Ͻ5.8 m in diameter (NES-spacer ϭ Babyhaler Ͼ Aerochamber-Infant; p Ͻ 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 NESspacer than with the Aerochamber-Infant or the Babyhaler (5.40 Ϯ 2.40%, 2.91 Ϯ 0.86%, 0.52 Ϯ 0.46%, respectively; p ϭ 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants. Small-volume spacer devices fitted with a face mask and inspiratory/expiratory valves have been developed for delivering pressurized metered-dose inhaler drugs to infants and newborns with various respiratory diseases (1-4). However, little is known about the ability of these spacer devices to deliver a significant amount of drug to the lungs of spontaneous breathing infants and a fortiori in intubated and mechanically ventilated infants and newborns.The radiotracer technique is the only method available for direct estimation of aerosol deposition in vivo. This technique is commonly used in adults, and has been used in several studies in infants (5-7). However, the exposure of small infants to radioisotopes remains a concern. Thus, performance is often projected from in vitro experiments (8 -10) or in vitro lung models (11,12), with data obtained at lower inspiratory flow rates and higher tidal volumes through the spacer devices than what would be encountered in clinical practice. Animal "infant" models (13, 14) may be suitable alternatives to assess pulmonary deposition of labeled drugs. Usually, rabbits are tracheotomized, mechanically ventilated, and killed, but this animal model poorly reflects the lung deposition of drug administered through spacer devices in spontaneously breathing children. Because oropharyngeal ...

Albuterol delivery via metered dose inhaler in a spontaneously breathing pediatric tracheostomy model

“…We think that these three elements are responsible for the superior performance of the device. These data are in agreement with those of Dubus et al, who compared albuterol delivery via pMDI in spontaneously breathing rabbits intubated with an ETT with an ID = 3 mm. They found that the valved holding chamber made of non‐electrostatic material was the most efficient one.…”

Aerosol Deposition in Neonatal Ventilation

“…In a model of anesthetized rabbits that were intubated with a 3.0-mm ETT, deposition of an aerosol administered via a spacer placed on the ventilator's inspiratory line or directly into the ETT ranged from 0.2 to 0.4% of the emitted dose (6,7). In conditions of uncontrolled ventilation in nonparalyzed rabbits, deposition reached a maximum of 5% of the emitted dose (7,9). The use of a jet nebulizer resulted in Ͻ1% of the charge deposited into the lungs of rabbits with a 3.5-mm ETT (4,5,8).…”

Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies

“…For example, in vivo studies on rats are common and different models were developed especially for BPD studies 25 . Other in vivo animal models exist, such as baboon 26 , macaque 27 , piglet 28 or rabbit 29 , and could be used as infant-like model for aerosol regional deposition studies. However, using animal models is expensive and time-consuming ( i .…”