Many devices (e.g., nebulizers and spacers) are used to deliver aerosol in a non-invasive ventilation circuit (NIV) without any special recommendation. The aim of the present work was to compare the doses delivered from seven different aerosol delivery systems when placed in the NIV using automatic continuous positive airway pressure (Auto-CPAP). Three spacers and three vibrating mesh nebulizers were compared to a Sidestream jet nebulizer (SIDE). Each device was placed proximal to a breathing simulator in a standard NIV circuit with a 500 ml tidal volume, 15 breaths/min and a 1:3 inspiratory-expiratory ratio. Two ml of salbutamol solution containing 10,000 μg was nebulized using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO and SIDE. Twelve metered dose inhaler doses, containing 100 μg salbutamol each, were delivered using AeroChamber MV (AC), AeroChamber Vent (VC) and AeroChamber Mini (MC). Total emitted dose (TED) and its percentage were determined. Aerodynamic droplet characteristics were measured using cooled Andersen Cascade Impactor. The vibrating mesh nebulizers used had significantly more (p < 0.001) TED compared to the jet nebulizer. The spacers used had higher TED % (p < 0.001) compared to the nebulizers. The fine particle fraction of SIDE was the highest (p = 0.021) and mass median aerodynamic diameter of the spacers was the smallest (p = 0.001). The fine particle dose from vibrating mesh nebulizers was the greatest (p = 0.02). Aerosol delivery in Auto-CPAP NIV is feasible; however, aerosol delivery method should be chosen or substituted with care. 2 mg delivered from a spacer would be equivalent to 3 mg nebulized from a vibrating mesh nebulizer and 5 mg nebulized from a Sidestream.

BACKGROUND: There has been a growing trend toward delivering aerosolized medications using high-flow nasal cannula (HFNC). In some cases, patients who do not require high-flow oxygen to maintain adequate oxygenation may benefit from aerosol delivery while receiving low-flow oxygen via HFNC. The objective of this study was to quantify and compare the relative pulmonary and systemic delivery of salbutamol, with 2 different nebulizers, in patients with COPD receiving low-flow oxygen therapy through an HFNC. METHODS: Subjects were randomized to receive study doses of 5 mg salbutamol nebulized by either a jet nebulizer or a vibrating mesh nebulizer with a T-piece or spacer on days 1, 3, and 5 of admission. Subjects using the large spacer also received 2 puffs (100 μg each) of salbutamol via a pressurized metered-dose-inhaler prior to the nebulizer dose. Urinary salbutamol excretion 30 min post-inhalation and pooled samples of urinary salbutamol excretion up to 24 h post-inhalation were measured. On day 2, ex vivo studies were performed with salbutamol collected on filters placed between the HFNC and nebulizer, with drug eluted from filters and analyzed to determine inhaled dose. RESULTS: Twelve subjects (6 females), age 51.3 ± 11.2 y, were included. The vibrating mesh nebulizer demonstrated higher urinary salbutamol excretion at 30 min and 24 h post-inhalation compared to a jet nebulizer ( P = .001 and P = .02, respectively). No significant difference was found between the T-piece and large-spacer configurations, even though the spacer provided a significantly larger emitted aerosol dose at the opening of the HFNC ( P = .002). CONCLUSIONS: Aerosolized medication could be efficiently combined with low-flow oxygen, via HFNC, in COPD subjects without the need to interrupt the gas supply. The vibrating mesh nebulizer delivered larger doses to subjects compared to the jet nebulizer. However, there was no benefit of using the large spacer with HFNC in low-flow delivery, because the small inner diameter of the HFNC does not allow larger aerosol droplet sizes (preserved by the spacer) to reach the subject.

BACKGROUND: The aim of this work was to determine the effect of fill volume and humidification change on aerosol delivery during single-limb noninvasive ventilation (NIV). METHODS: Four groups were recruited, each consisting of 12 subjects (6 females) with COPD receiving NIV. Groups 1 and 3 received inhaled salbutamol with a vibrating mesh nebulizer, and Groups 2 and 4 received inhaled salbutamol with a jet nebulizer. The in vivo study was carried out on days 1 and 3. In groups 1 and 2, 2 fill-volumes were delivered to each subject; 1 mL 5,000 μg/mL salbutamol respirable solution used as it is or diluted to a total of 2 mL using normal saline. In groups 3 and 4, 1 mL 5,000 μg/mL salbutamol respirable solution diluted to 2 mL total volume using normal saline was delivered to each subject with and without humidification. Unchanged salbutamol in urine at 30 min (USAL0.5) and in pooled urine at 24 h (USAL24) was determined. On day 2, the ex vivo study was carried out on subjects using the same experimental setting with a filter placed proximal to their face mask for collection of total inhaled dose of salbutamol (aerosol emitted). RESULTS: The vibrating mesh nebulizer delivered higher USAL0.5, USAL24, and aerosol emitted compared to the jet nebulizer at all fill volumes and humidification conditions ( P < .001). Increasing fill volume from 1 mL to 2 mL resulted in a significant increase in USAL0.5, USAL24, and aerosol emitted from the jet nebulizer ( P < .05) with an insignificant effect on the vibrating mesh nebulizer. A 2-mL fill volume with the jet nebulizer delivered USAL24 and aerosol emitted comparable to those of 1 mL with the vibrating mesh nebulizer with significantly longer nebulization times ( P < .001). Humidification had an insignificant effect on aerosol delivery. CONCLUSIONS: Increasing the fill volume of a jet nebulizer is essential to increase the amount of inhaled medication reaching a subject. In contrast, there is no need to increase fill volumes when using a vibrating mesh nebulizer. There is no need to switch off the humidifier while delivering aerosol through a single-limb NIV circuit.

BACKGROUND: Predosing patients with COPD with salbutamol by using a pressurized metered-dose-inhaler (pMDI) as a bronchodilator was hypothesized to improve the distribution of the subsequent nebulized dose. This study determined the effect of a pMDI preliminary bronchodilator dose on the aerosol delivered by a mesh nebulizer during single-limb noninvasive ventilation. METHODS: Twelve subjects with COPD who received noninvasive ventilation were enrolled in a randomized, open-label, urinary pharmacokinetic study. A bi-level ventilator with a dry single-limb circuit and the fixed expiratory port was set in the spontaneous mode, with initial inspiratory and expiratory pressures of 20 and 5 cm H ₂ O respectively, a 1:3 inspiratory-expiratory ratio, and 15 breaths/min. Salbutamol was administered via a mesh nebulizer with a large spacer or T-piece placed between the fixed-orifice expiratory valve and the oronasal mask. In vivo dosing methods were randomized for days 1, 3, and 5 of the study. On each day, a 1-mL respirable solution that contained 5,000 μg salbutamol was nebulized by using a mesh nebulizer with 3 setting: (1) T-piece, (2) large spacer, and (3) large spacer plus pMDI. Only with the large spacer plus pMDI setting, 2 pMDI doses, which contained 100 μg salbutamol each, were actuated before nebulization. Urine samples were collected at 0.5 h (as an index of pulmonary bioavailability) and pooled up to 24 h after dosing (as an index of systemic absorption). On day 2, ex vivo studies were performed for the 3 setting with salbutamol collected onto filters placed before the mask. The drug was eluted from the filters and analyzed to determine the inhaled dose. RESULTS: A large spacer plus pMDI showed a trend to deliver a higher fraction (percentage of nominal dose) of both ex vivo filters and 0.5-h urinary salbutamol. The 0.5-h urinary salbutamol excreted with a large spacer plus pMDI (1.99%) was larger than with the T-piece (1.73%) and large spacer (1.78%). This trend did not extend to the 24-h levels, in which bioavailability with the large spacer plus pMDI (49.9%) was lower than with the T-piece (52.8%) and with the large spacer (54.3%). However, no differences were significant. CONCLUSIONS: The T-piece and large spacer were equally efficient for salbutamol delivery from the mesh nebulizer in patients with COPD and on single-limb noninvasive ventilation. Adding a preliminary bronchodilator dose by pMDI prenebulization showed a trend toward greater pulmonary bioavailability of nebulized salbutamol and may be worth considering to maximize delivery of salbutamol to patients who are severely ill.