Dry-Powder Inhaler Delivery of Aerosolized Tobramycin with in Vitro Models of Tracheostomized Paediatric Patients

Abstract

Abstract BACKGROUND: Tracheostomies are not uncommon in the pediatric population and are necessary in situations such as long-term cardiorespiratory compromise or fixed airway obstructions. Delivery of aerosolized medication allows for directed therapy to the lungs and is an important component of therapeutic management. However there is surprisingly little literature that quantifies delivery of aerosol medication through tracheostomies. During Pseudomonas aeruginosa respiratory infections, tobramycin is frequently administered using nebulizers, like the PARI LC Plus (LC Plus), which are known to have drawbacks, most notably the time burden. Dry-powder inhalers, like the TOBI Podhaler (Podhaler), can deliverhigher payloads of medication to the airway and in a shorter time. Currently no data exists that evaluates aerosol delivery of drypower inhalers through tracheostomies. OBJECTIVES: The aim of the study is to investigate and quantify the amount of aerosolized tobramycin delivered to the lungs of in vitro trache-ostomized spontaneously breathing pediatric patient models when using the Podhaler in comparison to the current gold-standard, the LC Plus nebulizer. DESIGN/METHODS: In vitro tracheostomized models of a 6- and 12-year old trachea were created. Aerosol was delivered to the tracheos-tomy models with the LC Plus and Podhaler, using their respective breathing patterns. Aerosolized medication was captured on a Respirgard II filter placed at the distal end of the trachea (lung filter), the amount was quantified using a colorimetric tobramycin assay and expressed as a percent charge of emitted dose. Drug trapped on the lung filter represented the amount of aerosol delivered to the respiratory tract. Three devices of each type were tested in triplicate to ensure repeatability. RESULTS: A total of 36 runs (LC Plus: 18, Podhaler: 18) were completed and demonstrated the Podhaler’s consistent outperformance of the LC Plus. The results are expressed as mean ± standard deviation in percent charge (LC Plus vs. Podhaler); all runs (24.1±3.7 vs. 86.6±8.7), 6-year old model (23.2±2.6 vs. 82.1±9.9) and 12-year old (24.1±4.5 vs. 86.6±4.2). The results were statistically significant (P-values <<< 0.01), based on an unpaired t-tests due to unequal variance. CONCLUSION: The study’s findings demonstrate that the Podhaler significantly outperformed the LC plus in delivering tobramycin to in vitro pediatric tracheostomized models. These results can be generalized to the tracheostomized adult population, and suggest that tobramycin delivery using the Podhaler is a feasible option and a future clinical study is warranted.