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

Abstract

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 "wetside" 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 6 SD (all data) 31.1% 6 6.45; no. 5 83. Small significant differences were seen with humidification for all modes (humidified 36.1% 6 5.60, no. 5 26; bypassable valved HME 28.8% 6 5.51, no. 5 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 lm. The V T was unaffected (exhaled V T-5.0 6 12.9 mL; P 5 .75) and test lung (test lung volume 25 6 14.5 mL; P 5 .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.

Reproducible Dosing With a Jet Nebulizer During Invasive Mechanical Ventilation

“…In contrast to previous recommendations to place the nebulizer on the ventilator (dry) side of the humidifier, 11 the investigators placed the nebulizer on the patient (wet) side at the humidifier outlet. 10 In their article, they reported their findings in a bench model that tested the effects of this nebulizer system on aerosol delivery with 3 different ventilators and a wide variety of clinically relevant settings with and without active humidification. 10 Difficulty in achieving reproducible dosing has been a major limitation of nebulizers.…”

“…10 In their article, they reported their findings in a bench model that tested the effects of this nebulizer system on aerosol delivery with 3 different ventilators and a wide variety of clinically relevant settings with and without active humidification. 10 Difficulty in achieving reproducible dosing has been a major limitation of nebulizers. Even minor changes in the technique of administration significantly impact the efficiency of drug delivery.…”

“…Even minor changes in the technique of administration significantly impact the efficiency of drug delivery. 4,12 Cuccia et al 10 showed that the inhaled mass with nebulizers in previous studies varied from 2.7 to 41% of the nominal dose. The variability in dosing efficiency could be attributed to several factors, such as nebulizer type, breathing pattern, nebulizer placement in the circuit, and the presence of humidity in the circuit.…”

“…The variability in dosing efficiency could be attributed to several factors, such as nebulizer type, breathing pattern, nebulizer placement in the circuit, and the presence of humidity in the circuit. 10 The salient feature of the current investigation is that the inhaled mass with the breath-actuated and breath - different ventilators, modes of ventilation, ventilator parameters, bias flows, and PEEPs. 10 Thus, a predictable drug dose could be delivered to patients receiving mechanical ventilation with this novel technology.…”

“…10 The salient feature of the current investigation is that the inhaled mass with the breath-actuated and breath - different ventilators, modes of ventilation, ventilator parameters, bias flows, and PEEPs. 10 Thus, a predictable drug dose could be delivered to patients receiving mechanical ventilation with this novel technology. The consistency of dosing represents a clear advantage for the delivery of drugs, such as antibiotics, that require reproducible delivery of high local concentrations in the lungs for a therapeutic effect.…”