Aerodynamic characteristics of aerosol delivery during invasive mechanical ventilation (IMV) are mostly determined by inserting cascade impactor in the circuit. Impactor might have some effect on airflow within IMV. Hence, the aim of the present study was to develop and evaluate new in vitro aerodynamic characterization methodology without affecting airflow in IMV. Breathing simulator was set in standard adult IMV circuit with inspiratory and expiratory pressures of 20 and 5 cm HO, 1:3 inspiratory-expiratory ratio, 15 breaths min, and tidal volume of 500 ml. Two ml of salbutamol solution containing 10,000 μg was nebulized using three different vibrating mesh nebulizers (VMNs) and Sidestream jet nebulizer (JET). Sixteen-metered doses, containing 100 μg salbutamol each, were delivered using three different spacers. Each device was placed in inspiration limb of Y-piece of ventilator tubing. Aerodynamic characteristics of aerosol delivered were measured using cooled Andersen cascade impactor, with mixing inlet connected to it. VMNs used had significantly more total mass in the impactor (p < .001) and fine particle dose (p < .001) compared to JET. Spacers used had higher total mass in the impactor percent (p < .001) and fine particle fraction compared to nebulizers. The in vitro IMV methodology setting suggested here showed encouraging results in comparison of different aerosol delivery systems in intubated patient.

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Background Continuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 μg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 μg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC). Results Low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP. Conclusions Our results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.

Background Both non-invasive ventilation and high flow oxygen therapy are preferred over low flow oxygen therapy in many conditions. Nebulizers, for aerosol delivery, can be used within them without interrupting the circuit. The present study aimed to compare the efficiency of drug delivery within high flow nasal cannula (HFNC) and biphasic positive airway pressure (BiPAP) ventilation mode using two different inspiratory positive airway pressures. The aerosol delivery was examined in HFNC system at low flow, 5 L min−1, and BiPAP non-invasive ventilation under 2 different pressures [high pressure; inspiratory positive airway pressure/expiratory positive airway pressure (IPAP/EPAP) of 20/5 cm water, and low pressure; IPAP/EPAP of 10/5 cm water]. The total inhalable dose (TID) was measured by inserting an Aerogen Solo nebulizer installed with 1 mL salbutamol respiratory solution (5000 μg mL−1) within the circuit, and the salbutamol was collected on an inhalation filter placed in a filter holder connected to a breathing simulator. The breathing simulator was adjusted at a tidal volume of 500 mL, respiratory rate of 15 breaths min−1, and inhalation to exhalation (I:E) ratio of 1:1 for the adult setting. In each technique of the three (HFNC, and low, and high-pressures BiPAP), TID was determined 5 times (n = 5). For particle size characterization, cooled Anderson Cascade Impactor (ACI) was inserted instead of the inhalation filter and the breathing simulator with the same scheme. In each technique of the three, particle size characterization was determined 3 times (n = 3). Results The BiPAP mode at low inspiratory pressure had the highest TID, followed by HFNC at flow 5 L min−1, then BiPAP mode at high inspiratory pressure. There was a significant difference only between low and high inspiratory pressure modes of BiPAP mode. Low-inspiratory pressure BiPAP delivered the highest mean ± SD fine particle dose (FPD). It was significantly higher than that delivered in high inspiratory pressure BiPAP, and HFNC. Also, FPD in HFNC was significantly higher than that in high inspiratory pressure BiPAP. HFNC system had the smallest mass median aerodynamic diameter (MMAD) and the highest FPF followed by low then high inspiratory pressure BiPAP. Conclusions Increasing the inspiratory positive airway pressure in BiPAP, from 10 to 20 cm water, decreased the total inhalable dose and FPF nearly by half. Low inspiratory pressure BiPAP delivered the highest TID and FPD. The HFNC system at low oxygen flow resulted in the least MMAD, and the highest FPF. Using HFNC delivered a TID that was non-significant from that delivered by low inspiratory pressure BiPAP. Graphical Abstract

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