Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients.

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.

Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients.

Objectives: This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. Method: COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose.Results: The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(p < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (p < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (p < 0.001).Conclusion: Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.

Inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during invasive mechanical ventilation.

BACKGROUND: Patient receiving invasive mechanical ventilation (IMV) may benefit from medical aerosol, but guidance on dosing with different aerosol devices is limited to in-vitro studies. The study was designed to compare aerosol delivery with five different types of aerosol generators during IMV. METHOD: In randomized design, 60 (30 female) mechanically ventilated chronic obstructive pulmonary disease (COPD) patients were assigned to one of 5 groups. Groups 1-4 received 5000 µg salbutamol using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO vibrating mesh and jet nebulizers (JN), respectively, while group 5 received 800 µg (8 puffs) of salbutamol via metered dose inhaler with AeroChamber-MV (MDI-AC). All devices were place in the inspiratory limb of ventilator downstream from humidifier which was switched off while delivery. Patients received the inhaled dose on day 1 and provided urine 30 post dosing. They also recived the same inhaled dose with a filter before the endotracheal tube on day 2. Amount of salbutamol excreted in urine 30 min post inhalation and the amount deposited on the filter from all the COPD patients were determined as indeces of pulmonary deposition and systemic absorption, respectively. RESULTS: No significant difference was found between the 3 vibrating mesh nebulizers (VMNs). The in-vivo and ex-vivo testing showed that all the VMNs resulted in better aerosol delivery compared to JN (p < 0.01). However, MDI-AC resulted in better aerosol delivery to VMNs but must be accompanied with careful attention and proper delivery of MDI-AC doses by healthcare provider. CONCLUSIONS: VMNs can be exchanged with each other, with no dose adjustment. However, dose adjustment is a must when replacing VMNs by JN or MDI-AC. This similarity and difference between the 5 aerosol delivery methods suggest that for IMV patients, aerosol delivery methods should be chosen or substituted with care.

In vitro aerodynamic characteristics of aerosol delivered from different inhalation methods in mechanical ventilation.

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 H2O, 1:3 inspiratory-expiratory ratio, 15 breaths min-1, 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.