Effect of Tidal Volume and Nebulizer Type and Position on Albuterol Delivery in a Pediatric Model of Mechanical Ventilation

Berlinski, Ariel; Willis, Jessika

doi:10.4187/respcare.04013

Cited by 36 publications

(48 citation statements)

References 16 publications

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“…In contrast to findings in adult and pediatric models of conventional mechanical ventilation, [18][19][20][21] we found greater drug delivery with proximal placement of the VMN during infant conditions. The difference in findings can be explained in part by the circuit, VT, and breathing patterns used with different patient populations.…”

Section: Discussioncontrasting

confidence: 99%

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Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

et al. 2016

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Iloprost is a selective pulmonary vasodilator approved for inhalation by the Food and Drug Administration. Iloprost has been increasingly used in the management of critically ill neonates with hypoxic lung disease. This in vitro study was designed to test the hypothesis that aerosol drug delivery could be effectively administered to infants with both conventional ventilation and high-frequency oscillatory ventilation (HFOV). A neonatal test lung model configured with newborn lung mechanics was ventilated with a conventional ventilator and an HFOV with standard settings. A vibrating-mesh nebulizer was placed (1) proximal to the patient airway in the inspiratory limb between the humidifier probe and patient wye (conventional) as well as between the vent circuit and the endotracheal tube (ETT) for HFOV and (2) between the ventilator and humidifier (distal). Iloprost was nebulized in three separate runs using three new nebulizers in each of the circuit locations. A collecting filter was placed at the distal end of the ETT for each trial. Iloprost was quantified using highperformance liquid chromatography. The percentage of nominal dose delivered was greater with the nebulizer placed proximal to the airway for conventional ventilation (10.74% ± 2%) and HFOV (29% ± 2%) than with it placed in the distal position (2.96% ± 0.2% vs. 0.96% ± 0.8%, respectively; P < 0.05). Drug delivery in proximal position was nearly threefold greater during HFOV than during conventional ventilation. In conclusion, iloprost drug delivery was best achieved when the nebulizer was placed proximal to the patient airway during neonatal mechanical ventilation. Drug delivery appears to be more efficient during HFOV than during conventional ventilation.Keywords: neonatal ventilation, pediatric aerosol delivery, high-frequency ventilation, inhaled pulmonary vasodilation, infant hypoxic lung disease. Iloprost (Ventavis; Actelion Pharmaceuticals US) is a stable prostacyclin analog used in the treatment of pulmonary hypertension. It is pharmacologically similar to epoprostenol, with vasodilatory, vascular remodeling, and platelet inhibitory properties, but it is a more stable compound, with an elimination half-life of 20-30 minutes. 1The longer half-life than that of other prostacyclin formulations allows the drug to be delivered with less frequency. Iloprost was the first prostacyclin designed specifically for aerosolization and approved for inhalation in ambulatory adults with primary pulmonary hypertension using the I-neb AAD system (Philips Respironics, Netherlands), a vibrating-mesh smart nebulizer. The design of the I-neb precludes its use in a closed ventilator circuit. While researchers have described a strategy for aerosol delivery during adult mechanical ventilation, none have applied such strategies for use with iloprost in infants. 2 Iloprost inhalation has been reported to be of some benefit in the management of critically ill neonates and infants with hypoxic lung disease and pulmonary hypertension.3-17 Many neonates with sever...

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Section: Discussioncontrasting

confidence: 99%

“…Multiple investigators have described the impact of placement of a VMN in distal and proximal positions during simulated pediatric [19][20][21] and adult 18 mechanical ventilation. In an adult model without bias flow, Ari et al 18 reported twofold greater drug delivery with proximal versus distal position (prior to the humidifier).…”

Section: Discussionmentioning

confidence: 99%

Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

et al. 2016

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“…While there are differences between the studies at each flow rate, the overall trends remain similar. Direct comparisons between inhaled dose are difficult due to several factors influencing the drug available for inhalation, such as the position of components in the ventilator circuit, simulated breathing settings and humidification affect the inhaled dose [37][38][39]. Golshahi et al [40] reported that increasing the tubing length from 20 cm to 50 cm increased the deposition fraction in the tube from 1.2% to 13.3%; this compared with a tube of length 1.8 m used in the current study.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Fugitive Aerosols Released into the Environment during High-Flow Therapy

et al. 2019

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Background: Nebulised medical aerosols are designed to deliver drugs to the lungs to aid in the treatment of respiratory diseases. However, an unintended consequence is the potential for fugitive emissions during patient treatment, which may pose a risk factor in both clinical and homecare settings. Methods: The current study examined the potential for fugitive emissions, using albuterol sulphate as a tracer aerosol during high-flow therapy. A nasal cannula was connected to a head model or alternatively, a interface was connected to a tracheostomy tube in combination with a simulated adult and paediatric breathing profile. Two aerodynamic particle sizers (APS) recorded time-series aerosol concentrations and size distributions at two different distances relative to the simulated patient. Results: The results showed that the quantity and characteristics of the fugitive emissions were influenced by the interface type, patient type and supplemental gas-flow rate. There was a trend in the adult scenarios; as the flow rate increased, the fugitive emissions and the mass median aerodynamic diameter (MMAD) of the aerosol both decreased. The fugitive emissions were comparable when using the adult breathing profiles for the nasal cannula and tracheostomy interfaces; however, there was a noticeable distinction between the two interfaces when compared for the paediatric breathing profiles. The highest recorded aerosol concentration was 0.370 ± 0.046 mg m−3 from the tracheostomy interface during simulated paediatric breathing with a gas-flow rate of 20 L/min. The averaged MMAD across all combinations ranged from 1.248 to 1.793 µm by the APS at a distance of 0.8 m away from the patient interface. Conclusions: Overall, the results highlight the potential for secondary inhalation of fugitive emissions released during simulated aerosol treatment with concurrent high-flow therapy. The findings will help in developing policy and best practice for risk mitigation from fugitive emissions.

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“…However, we found one exception that with gas flow at 5 L/min, inhaled dose was higher with continuous than inspiration synchronized aerosol, which might be explained by the significant reduction of the washing out effects due to the extremely low flow, resulting in reservoir of aerosol during exhalation for continuous aerosol. In contrast, because of the low flow rate to carry aerosol, aerosol generated at the inspiratory phase might not be able to fully reach the trachea yet before exhalation [20,21]. Due to the concerns of the aerosol waste during exhalation, continuous VMN was found to generate higher inhaled dose when placed at the inlet of humidifier, using the circuit and humidifier chamber as reservoir during exhalation.…”

Section: Comparison Of Inspiration Synchronized Vs Continuous Vmn Plamentioning

confidence: 99%

In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery

Fink

2020

ICMx

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Background: Compared to continuous vibrating mesh nebulizer (VMN), inspiration synchronized VMN has shown increased inhaled dose during noninvasive ventilation; however, its use during aerosol delivery via high-flow nasal cannula (HFNC) is still unknown. Methods: An adult manikin was connected to a dual-chamber model lung, which was driven by a critical care ventilator to simulate spontaneous breathing. A HFNC system was utilized with temperature at 37°C while gas flow at 5, 10, 20, 40, and 60 L/min. Inspiration synchronized and continuous aerosol generation were compared at different positions (at the inlet of humidifier vs close to patient). One milliliter of albuterol (2.5 mg/mL) was used in each run (n = 3). Collection filter was placed at the trachea and was removed after each run. Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). Results: When nebulizer was placed close to patient, inhaled dose was higher with inspiration synchronized than continuous aerosol generation at all gas flows (p = 0.05) except at 5 L/min. When placed at the inlet of humidifier, compared to continuous, inspiration synchronized aerosol generated higher inhaled dose with gas flow set below 50% of patient inspiratory flow [23.9 (20.6, 28.3)% vs 18.1 (16.7, 19.6)%, p < 0.001], but lower inhaled dose with gas flow set above 50% of patient inspiratory flow [3.5 (2.2, 9.3)% vs 9.9 (8.2, 16.4)%, p = 0.001]. Regardless of breathing pattern, continuous aerosol delivered greater inhaled dose with nebulizer placed at humidifier than close to patient at all gas flows except at 5 L/min. Conclusion: When the HFNC gas flow was set higher than 50% of patient inspiratory flow, no significant advantage was found in inspiration synchronized over continuous aerosol. However, inspiration synchronized aerosol generated 30% more inhaled dose than continuous with gas flow set below 50% of patient inspiratory flow, regardless of nebulizer placement. Continuous nebulizer needs to be placed at the inlet of humidifier.

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Effect of Tidal Volume and Nebulizer Type and Position on Albuterol Delivery in a Pediatric Model of Mechanical Ventilation

Cited by 36 publications

References 16 publications

Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

Investigation of Fugitive Aerosols Released into the Environment during High-Flow Therapy

In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery

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