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

BACKGROUND: The present study tested a novel nebulizer and circuit that use breath enhancement and breath actuation to minimize ventilator influences. The unique circuit design incorporates “wet-side” jet nebulization (the nebulizer connected to the humidifier outlet port) to prevent unpredictable aerosol losses with active humidification. The system was studied using several ventilator brands over a wide range of settings, with and without humidification.

METHODS: During treatment, a 2-position valve directed all ventilator flow to the nebulizer, providing breath enhancement during inspiration. Aerosol was generated by air 50 psi 3.5 L/m triggered during inspiration by a pressure-sensitive circuit. Particles were captured on an inhaled mass filter. Testing was performed by using active humidification or bypassable valved heat and moisture exchanger (HME) over a range of breathing patterns, ventilator modes, and bias flows (0.5-5.0 L/m). The nebulizer was charged with 6 mL of radiolabeled saline solution. Mass balance was performed by using a gamma camera. Tidal volume was monitored by ventilator volume (exhaled V_T) and test lung volume. The Mann-Whitney test was used.

RESULTS: A total of 6 mL was nebulized within 1 h. Inhaled mass (% neb charge): mean ± SD (all data) 31.1% ± 6.45; no. = 83. Small significant differences were seen with humidification for all modes (humidified 36.1% ± 5.60, no. = 26; bypassable valved HME 28.8% ± 5.51, no. = 57 [P < .001]), continuous mandatory ventilation modes [P < .001], and pressure support airway pressure release ventilation modes [P < .001]. Mass median aerodynamic diameter ranged from 1.04 to 1.34 μm. The V_T was unaffected (exhaled V_T –5.0 ± 12.9 mL; P = .75) and test lung (test lung volume 25 ± 14.5 mL; P = .13). Bias flow and PEEP had no effect.

CONCLUSIONS: Breath enhancement with breath actuation provided a predictable dose at any ventilator setting or type of humidification. Preservation of drug delivery during active humidification is a new finding, compared with previous studies. The use of wall gases and stand alone breath actuation standardizes conditions that drive the nebulizer independent of ventilator design. Wet-side nebulizer placement at the humidifier outlet allows delivery without introducing aerosol into the humidification chamber.