Wet Side Breath-Enhanced Jet Nebulization: Controlling Drug Delivery During Mechanical Ventilation

Abstract

Background: Aerosol delivery during mechanical ventilation is uncontrolled and a function of duty cycle, bias flow, nebulizer position and methods of humidification. The present study tested a novel nebulizer and circuit (i-VENT, InspiRx, Somerset, NJ) that utilizes the energy of ventilator flow to generate aerosol (breath enhancement) combined with stand-alone breath actuation to minimize ventilator influences. The unique circuit design incorporates ‘wet side’ jet nebulization at the humidifier outlet designed to prevent unpredictable tube losses of generated aerosol with active humidification. The system was studied using several ventilator brands over a wide range of settings, with and without humidification. Methods: During a treatment, a 3-way valve directed all ventilator flow to the nebulizer. Aerosol was generated during inspiration by activation of a pressure sensitive breath-actuated circuit. O₂/air at 50 PSIG powered the nebulizer at a flow of 3.5 L/min. In vitro testing was performed using a heated wire circuit with humidification or by-passable/valved HME (BP-HME) on several ventilator brands over a range of breathing patterns, ventilator modes and bias flows (0.5-5 L/min). The nebulizer was charged with 6 mL of radiolabeled saline. Mass balance was performed using a gamma camera. Mann-Whitney test was used. Results: IM (% neb charge): mean ± SD [all data] 31.1 ± 6.33, n = 82; humidified 35.6 ± 5.47, n = 30; BP-HME 28.6 ± 5.31, n = 52. There was a significant difference in IM between humidification type (BP-HME and active humidification) for all data (P < .001), CMV modes (P < .001), and pressure support/APRV modes (P < .001). Bias flow had no effect, MMAD: Humidified 1.1 µm, BP-HME 0.9 µm. Conclusions: Breath enhancement with breath actuation overcomes much of the variability in aerosol delivery providing a predictable dose at any ventilator setting or type of humidification. Preservation of drug delivery during heated humidification is a new finding, compared to previous studies, with clinically minimal effects of humidification method. The use of wall gases and stand-alone breath actuation standardizes conditions driving the nebulizer independent of ventilator design. ‘Wet side’ nebulizer placement at the humidifier outlet allows delivery without introducing aerosol into the humidification chamber and circuit design allows nebulizer servicing without circuit interruption.