Improvement of an In Vitro Model to Assess Delivered Dose and Particle Size for a Vibrating Mesh Nebulizer During Mechanical Ventilation

J Aerosol Med Pulm Drug Deliv. 2018 Apr;31(2):94-102. doi: 10.1089/jamp.2017.1372. Epub 2017 Aug 16.

Abstract

Background: In an in vitro model of mechanical ventilation with gravity-dependent filter position we observed artificially high delivered doses resulting from liquid droplet collection and precipitation of aerosolized drug. We sequentially modified the model to obtain accurate reproducible measurements of delivered dose and particle size at endotracheal tube exit.

Methods: Stepwise changes in the model included (1) altering the endotracheal tube position to a gravity-independent position, (2) adding fluid traps, (3) humidifying air near the test lung, and (4) simplifying test lung and filters. Delivered dose of aerosolized vancomycin and losses in different compartments were assessed under low-flow and high-flow conditions, with or without circuit humidification. Droplet size distribution (DSD) of aerosolized Amikacin Inhalation Solution at endotracheal tube exit was measured by laser diffraction.

Results: Changing endotracheal tube position and adding traps allowed separation of liquid droplets and aerosolized drug, providing a delivered vancomycin dose of 35.1% (high flow). Active heated humidification of exhaled air significantly reduced delivered dose (21.0%) and dose variability. Simplification of the model to improve usability had no further effect on delivered dose, which was higher under low-flow than high-flow conditions, although there was no difference between humidified (high flow, 20.3%; low flow, 45.8%) and nonhumidified (high flow, 22.8%; low flow, 47.3%) conditions. With circuit humidification, drug loss decreased in endotracheal tube and nebulizer T-piece, whereas more drug was captured in traps. Lower inspiratory flow and humidity in the circuit were associated with higher Dv50 of aerosolized Amikacin Inhalation Solution at endotracheal tube exit.

Conclusions: We successfully modified our in vitro model of mechanical ventilation to allow more accurate measurement of the delivered dose of aerosolized vancomycin and DSD profile of aerosolized Amikacin Inhalation Solution at the endotracheal tube exit.

Keywords: aerosol distribution; inhaled therapy; nebulizer; ventilation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Amikacin / administration & dosage
  • Amikacin / pharmacokinetics
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Drug Delivery Systems*
  • Equipment Design
  • Humans
  • Humidity
  • Intubation, Intratracheal
  • Models, Biological*
  • Nebulizers and Vaporizers
  • Particle Size
  • Respiration, Artificial*
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacokinetics
  • Vibration

Substances

  • Aerosols
  • Anti-Bacterial Agents
  • Vancomycin
  • Amikacin