title: A Novel In-Line Delivery System to Administer Dry Powder Mannitol to Mechanically Ventilated Patients.
abstract: BACKGROUND
  Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol increases sputum clearance, and therefore, we developed a system to administer it to mechanically ventilated patients without disconnection from the ventilator.
  
  
  METHODS
  The inspiratory line from a ventilator was split by using a three-way valve into two parallel lines where one contains a humidifier for normal breathing cycle and the other line contains a dry powder inhaler (Osmohaler™). The inspiratory air went through the dry powder line and aerosolized the mannitol powder only when its administration to a patient is required. We determined the delivered dose and particle size distributions of emitted aerosols in vitro from 9.5 mm endotracheal and 7.5 mm tracheostomy tubes, with inspiratory airflow of 60, 70, and 80 L/min.
  
  
  RESULTS
  This novel setup was able to deliver 24.6% ± 3.33% of the 160 mg loaded dose mannitol powder (4 × 40 mg capsules) and 26.7% ± 2.19% of the 320 mg dose (4 × 80 mg capsules) when the endotracheal tube was used. With the shorter tracheostomy tube, the delivery dose increased to 35.6% ± 3.01% and 39.5% ± 2.04% of the 160 and 320 mg doses, respectively. The volume median diameters of the aerosols were in the respirable range with the largest value being 5.17 ± 0.87 μm.
  
  
  CONCLUSIONS
  This delivery system has been shown to consistently deliver a high respirable dose of mannitol powder. Since this setup does not require disconnection of patients from the ventilator, it is safer for hypoxemic patients and easier to be adapted in a real clinical use.
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Benny
authors.initials: B
authors.lastname: Feng
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Patricia
authors.initials: P
authors.lastname: Tang
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Sharon Shui Yee
authors.initials: SS
authors.lastname: Leung
authors.affiliation: 2 Department of Intensive Care, Royal Brisbane Women's Hospital , Herston, Australia .|3 Burns, Trauma and Critical Care Research Centre, University of Queensland , Queensland, Australia .
authors.forename: Jayesh
authors.initials: J
authors.lastname: Dhanani
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D004867:Equipment Design; D006801:Humans; D066298:In Vitro Techniques; D007442:Intubation, Intratracheal; D008353:Mannitol / Q000008:administration & dosage*; D010316:Particle Size; D012121:Respiration, Artificial; D013183:Sputum / Q000378:metabolism; D014139:Tracheostomy
chemical_list: D000336:Aerosols; D008353:Mannitol
keywords: and intensive care; dry powder aerosol; mannitol powder; mechanically ventilated patients; sputum clearance