Multidrug Aerosol Delivery During Mechanical Ventilation

Abstract

Background: In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as bronchodilators or antibiotics are needed, vasodilator therapy may be interrupted. This study assesses aerosol systems designed for simultaneous delivery of two aerosols using continuous nebulization and bolus injection without interruption or circuit disconnection. Methods: One i-AIRE dual-port breath-enhanced jet nebulizer (BEJN) or two Aerogen^® Solo vibrating mesh nebulizers (VMNs) were installed on the dry side of the humidifier. VMN were stacked; one for infusion and the second for bolus drug delivery. The BEJN was powered by air at 3.5 L/min, 50 psig. Radiolabeled saline was infused at 5 and 10 mL/h with radiolabeled 3 and 6 mL bolus injections at 30 and 120 minutes, respectively. Two adult breathing patterns (duty cycle 0.13 and 0.34) were tested with an infusion time of 4 hours. Inhaled mass (IM) expressed as % of initial syringe activity (IM%/min) was monitored in real time with a ratemeter. All delivered radioaerosol was collected on a filter at the airway opening. Transients in aerosol delivery were measured by calibrated ratemeter. Results: IM%/h during continuous infusion was linear and predictable, mean ± standard deviation (SD): 2.12 ± 1.45%/h, 2.47 ± 0.863%/h for BEJN and VMN, respectively. BEJN functioned without incident. VMN continuous aerosol delivery stopped spontaneously in 3 of 8 runs (38%); bolus delivery stopped spontaneously in 3 of 16 runs (19%). Tapping restarted VMN function during continuous and bolus delivery runs. Bolus delivery IM% (mean ± SD): 20.90% ± 7.01%, 30.40% ± 11.10% for BEJN and VMN, respectively. Conclusion: Simultaneous continuous and bolus nebulization without circuit disconnection is possible for both jet and mesh technology. Monitoring of VMN devices may be necessary in case of spontaneous interruption of nebulization.

Keywords: administration; aerosols; drug delivery; inhalation; mechanical; nebulizers and vaporizers; ventilators.

FIG. 1.

Experimental setup: The ventilator circuit during continuous infusion with the i-AIRE BEJN prototype with dual-medication port adaptor. BEJN, breath-enhanced jet nebulizer.

FIG. 2.

Stacked Aerogen Solo VMN and two controllers. One VMN and controller designated for continuous infusion (left) and designated bolus VMN and controller (right). VMN, vibrating mesh nebulizer.

FIG. 3.

i-AIRE BEJN prototype with dual-medication port adaptor. Continuous infusion line is screwed on to nebulizer port with leur lock cap outfitted with medication port equipped with tethered cap and plug. Both nebulizer ports empty into a single nebulizer bowl.

FIG. 4.

Depicts i-AIRE BEJN at 5 mL/h and DC 0.13, including slopes and quantification of contribution of continuous infusion used for calculation of IM% from bolus syringe deposited on filter. Vertical axis: IM%, expressed as a % of initial syringe charge; Horizontal Axis: run time (minutes). DC, duty cycle; IM, inhaled mass.

FIG. 5.

i-AIRE BEJN (■) and Aerogen Solo VMN (•) during continuous infusion at 5 mL/h and DC 0.13. Three milliliters bolus injected into nebulizer at 30 minutes, 6 mL bolus added at 120 minutes. IM filter changed at 90 and 160 minutes. Aerogen Solo VMN: 6 mL bolus nebulizer spontaneously stopped at 125 minutes, tapped and restarted at 135 minutes with bolus consumed by 145 minutes. IM filter changed at 90 and 160 minutes. Vertical Axis: IM%, expressed as a % of initial syringe charge; horizontal axis: run time (minutes).