title: Optimal delivery of aerosols to infants during mechanical ventilation.
abstract: OBJECTIVE
  The objective of this study was to determine optimal aerosol delivery conditions for a full-term (3.6 kg) infant receiving invasive mechanical ventilation by evaluating the effects of aerosol particle size, a new wye connector, and timing of aerosol delivery.
  
  
  METHODS
  In vitro experiments used a vibrating mesh nebulizer and evaluated drug deposition fraction and emitted dose through ventilation circuits containing either a commercial (CM) or new streamlined (SL) wye connector and 3-mm endotracheal tube (ETT) for aerosols with mass median aerodynamic diameters of 880 nm, 1.78 μm, and 4.9 μm. The aerosol was released into the circuit either over the full inhalation cycle (T1 delivery) or over the first half of inhalation (T2 delivery). Validated computational fluid dynamics (CFD) simulations and whole-lung model predictions were used to assess lung deposition and exhaled dose during cyclic ventilation.
  
  
  RESULTS
  In vitro experiments at a steady-state tracheal flow rate of 5 L/min resulted in 80-90% transmission of the 880-nm and 1.78-μm aerosols from the ETT. Based on CFD simulations with cyclic ventilation, the SL wye design reduced depositional losses in the wye by a factor of approximately 2-4 and improved lung delivery efficiencies by a factor of approximately 2 compared with the CM device. Delivery of the aerosol over the first half of the inspiratory cycle (T2) reduced exhaled dose from the ventilation circuit by a factor of 4 compared with T1 delivery. Optimal lung deposition was achieved with the SL wye connector and T2 delivery, resulting in 45% and 60% lung deposition for optimal polydisperse (∼1.78 μm) and monodisperse (∼2.5 μm) particle sizes, respectively.
  
  
  CONCLUSIONS
  Optimization of selected factors and use of a new SL wye connector can substantially increase the lung delivery efficiency of medical aerosols to infants from current values of <1-10% to a range of 45-60%.
authors.affiliation: 1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University , Richmond, VA.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.forename: Mandana
authors.initials: M
authors.lastname: Azimi
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000336:Aerosols / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000592:standards*; D004867:Equipment Design; D006801:Humans; D057446:Hydrodynamics; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D001239:Inhalation / Q000502:physiology; D007442:Intubation, Intratracheal; D008168:Lung / Q000502:physiology; D008954:Models, Biological; D010316:Particle Size; D012121:Respiration, Artificial / Q000295:instrumentation*; D013997:Time Factors
chemical_list: D000336:Aerosols
keywords: CFD simulations; Monte Carlo modeling; aerosols; mechanical ventilation; nebulization; neonate; respiratory drug delivery; streamlined wye