Optimizing dry powder delivery during invasive mechanical ventilation via circuit absolute humidity control

Area of Science:

• Pulmonary drug delivery
• Mechanical ventilation
• Inhaler technology

Background:

• Dry powder inhalers (DPIs) are challenging to use during invasive mechanical ventilation (IMV) due to low patient inspiratory effort and humidity interference.
• Existing ventilator circuits with heated humidification can negatively impact DPI powder dispersion and drug delivery efficiency.
• Efficient DPI delivery is crucial for administering inhaled therapies to mechanically ventilated patients.

Purpose of the Study:

• To evaluate the efficacy of a ventilator-actuated, enclosed DPI chamber with adjustable humidification for drug delivery during IMV.
• To determine the impact of varying absolute humidity (AH) levels on inhaled drug dose and particle size distribution.
• To assess the influence of endotracheal tube (ETT) size and tidal volume (VT) on DPI performance under IMV conditions.

Main Methods:

• An in vitro invasive mechanical ventilation model was used with a capsule DPI (indacaterol) in an enclosed delivery chamber.
• Absolute humidity was precisely controlled from 0 to 44 mg/L AH, and compared to a standard pass-over humidifier.
• Drug delivery was assessed across different tidal volumes (400-800 mL) and endotracheal tube sizes (7.5 and 9.5 mm ID).

Main Results:

• Inhaled drug dose exhibited a bidirectional dependence on humidity, peaking at 22 mg/L AH (39.9%) and decreasing significantly at high humidity (44 mg/L AH, 10.0%).
• Larger ETT diameter (9.5 mm) reduced ETT deposition and increased inhaled dose at low humidity compared to a smaller ETT (7.5 mm).
• Particle size distribution (MMAD, GSD) remained relatively stable, but fine particle fraction (<5 µm) decreased with increasing humidity.

Conclusions:

• A ventilator-actuated, enclosed DPI system with controllable humidification enables efficient drug delivery during IMV.
• Optimal DPI performance is achieved at intermediate humidity levels (around 22 mg/L AH), with reduced efficacy at humidity extremes.
• Controllable humidification is critical for successful implementation of DPI therapy in mechanically ventilated patients.