Factors Determining Continuous Infusion Aerosol Delivery During Mechanical Ventilation.

BACKGROUND: Continuous nebulization of prostacyclins and albuterol by infusion pump during mechanical ventilation evolved as a popular off-label treatment for severe hypoxemic respiratory failure and asthma. Most institutions use a vibrating mesh nebulizer. A new breath-enhanced jet nebulizer is a potential alternative. This study was designed to compare these devices to better define factors influencing continuous infusion aerosol delivery. Device function, ventilator settings, and infusion pump flow were studied in vitro. METHODS: Using a bench model of adult mechanical ventilation, radiolabeled saline was infused at 6 flows (1.5-12 mL/h) into test nebulizers; 4 examples of each were used in rotation to test device reproducibility. Four breathing patterns with duty cycles (percentage of inspiratory time) ranging from 0.13 to 0.34 were tested. The vibrating mesh nebulizer was installed on the "dry" side of the heated humidifier (37°C). The breath-enhanced jet nebulizer, installed on the "wet" side, was powered by air at 3.5 L/min and 50 psi. Infusion time was 1 h. Inhaled mass of aerosol was collected on a filter at the airway opening. Inhaled mass was expressed as the percentage of the initial syringe radioactivity delivered per hour. Radioactivity deposited in the circuit was measured with a gamma camera. Data were analyzed with multiple linear regression. RESULTS: Variation in inhaled mass was significantly explained by pump flow and duty cycle (R2 0.92) and not by nebulizer technology. Duty cycle effects were more apparent at higher pump flow. Vibrating mesh nebulizers failed to nebulize completely in 20% of the test runs. Mass balance indicated that vibrating mesh nebulizers deposited 15.3% in the humidifier versus 0.2% for breath-enhanced jet nebulizer. CONCLUSIONS: Aerosol delivery was determined by infusion pump flow and ventilator settings with comparable aerosol delivery between devices. The breath-enhanced jet nebulizer was more reliable than the vibrating mesh nebulizer; 10-12 mL/h was the maximum infusion flow for both nebulizer technologies.

Comparison of Vibrating Mesh, Jet, and Breath-Enhanced Nebulizers During Mechanical Ventilation.

BACKGROUND: This study compared 3 nebulizer technologies for inter- and intradevice reproducibility, humidification, and fill volume sensitivity during mechanical ventilation: a breath-enhanced jet nebulizer, a vibrating mesh nebulizer, and a jet nebulizer. The breath-enhanced jet nebulizer featured a new design located on the wet side of the humidifier to reduce aerosol loss and potential humidifier contamination. The vibrating mesh nebulizer and the jet nebulizer were placed on the dry side. METHODS: Aerosol delivery was measured using multiple ventilator settings (inspiratory time = 0.45-1.01 s). Using radiolabeled saline and a gamma camera, bench studies were performed using a ventilator to test 4 breathing patterns. Four scenarios were assessed during testing: 3 mL and 6 mL fill volumes with and without heated wire humidification. Measurements included inhaled mass (as a percentage of the nebulizer charge), nebulizer residual, mass balance, and aerosol particle size distribution. Statistics were determined using Mann-Whitney and linear regression. RESULTS: The inhaled mass for the breath-enhanced jet nebulizer was 10.5-29.2% and was affected by fill volume (P = .004) but not by humidity. The inhaled mass for the vibrating mesh nebulizer was 0.9-33% and was unaffected by fill volume and humidity. The inhaled mass for the jet nebulizer was 2.5-25.9% and was affected by both fill volume (P = .009) and humidity (3 mL, P = .002). The inhaled mass for the vibrating mesh nebulizer was more variable due to random failures to achieve complete nebulization, and inhaled mass correlated closely with residual mass: IM% = -0.233(Residual%) + 24.3, r2 = 0.67, P < .001. For all devices, large particles were lost in the ventilator tubing; large particles were also lost in the humidifier for the vibrating mesh nebulizer (17% nebulizer charge), resulting in similar particle distributions (mass median aerodynamic diameter 1.33-1.95 µm) for all devices. CONCLUSIONS: Nebulization with the breath-enhanced jet nebulizer was less sensitive to humidification than the jet nebulizer. Delivery via the vibrating mesh nebulizer was not predictable, with random failure to empty (55% experimental runs). All devices delivered similar particle distributions. Wet-side aerosol delivery avoids humidifier contamination, and breath-enhanced technology can ensure better control of drug delivery.

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 VT) 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 VT was unaffected (exhaled VT -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.