Aerosolized Albuterol Sulfate Delivery under Neonatal Ventilatory Conditions: <i>In Vitro</i> Evaluation of a Novel Ventilator Circuit Patient Interface Connector

Mazela, Jan; Chmura, K; Kulza, Maksymilian; Henderson, Christopher; Gregory, Timothy J.; Moskal, Arkadiusz; Sosnowski, Tomasz R.; Florek, Ewa; Kramer, Lisa A.; Keszler, Martin

doi:10.1089/jamp.2012.0992

Cited by 23 publications

(22 citation statements)

References 16 publications

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“…(11)(12)(13)(14) This extremely low delivery efficiency has been consistently demonstrated based on in vitro experiments (13,14) and animal models, (11,13,15) and in humans. (16) Newer vibrating mesh and ultrasonic nebulizers have significantly increased lung delivery efficiency of aerosols for ventilated infants to a value of approximately 10% in some cases.…”

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confidence: 93%

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Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

Longest

Azimi

Hindle

2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Purpose: The objective of this study was to determine optimal aerosol delivery conditions for a full-term (3.6 kg) infant receiving invasive mechanical ventilation by evaluating the effects of aerosol particle size, a new wye connector, and timing of aerosol delivery. Methods: In vitro experiments used a vibrating mesh nebulizer and evaluated drug deposition fraction and emitted dose through ventilation circuits containing either a commercial (CM) or new streamlined (SL) wye connector and 3-mm endotracheal tube (ETT) for aerosols with mass median aerodynamic diameters of 880 nm, 1.78 lm, and 4.9 lm. The aerosol was released into the circuit either over the full inhalation cycle (T1 delivery) or over the first half of inhalation (T2 delivery). Validated computational fluid dynamics (CFD) simulations and whole-lung model predictions were used to assess lung deposition and exhaled dose during cyclic ventilation. Results:In vitro experiments at a steady-state tracheal flow rate of 5 L/min resulted in 80-90% transmission of the 880-nm and 1.78-lm aerosols from the ETT. Based on CFD simulations with cyclic ventilation, the SL wye design reduced depositional losses in the wye by a factor of approximately 2-4 and improved lung delivery efficiencies by a factor of approximately 2 compared with the CM device. Delivery of the aerosol over the first half of the inspiratory cycle (T2) reduced exhaled dose from the ventilation circuit by a factor of 4 compared with T1 delivery. Optimal lung deposition was achieved with the SL wye connector and T2 delivery, resulting in 45% and 60% lung deposition for optimal polydisperse (*1.78 lm) and monodisperse (*2.5 lm) particle sizes, respectively. Conclusions: Optimization of selected factors and use of a new SL wye connector can substantially increase the lung delivery efficiency of medical aerosols to infants from current values of < 1-10% to a range of 45-60%.

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confidence: 93%

“…However, this approach may not be practical for modifying the wye connector where a 90°change in flow direction is required. In a recent study by Mazela et al, (12) a redesigned wye, referred to as the VC connector, was shown to increase emitted dose (ED) in a premature neonate in vitro model. As an alternative approach, Longest et al…”

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confidence: 99%

Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

Longest

Azimi

Hindle

2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…The system considered in this study delivers humidity through the nebulization of an aqueous solution to avoid dehydrating the airways (Ari and Fink 2015). Using a heated and humidified line, Mazela et al (2014) delivered 6.6% of a nominal AS dose to the end of the Y-connector in a mechanical ventilation system; however, an ETT was not considered. This system used a novel VC connector to bypass bias flow and improve delivery of a jet nebulizer providing a drug delivery rate of 2.9 μg/min (Mazela et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…A macaque animal model of a ventilated infant was used to demonstrate a lung delivery efficiency of 12.6 – 14% of the aerosolized dose through a 3 mm infant endotracheal tube (ETT) using a VMN synchronized with inspiration and without ventilator bias flow (Dubus et al, 2005). Using a jet nebulizer in an in vitro model of a ventilated premature infant, with a new connector to separate nebulizer and ventilation gas bias flow, Mazela et al (2014) increased albuterol sulfate delivery efficiency from 1% or less through the commercial Y-connector to a maximum of approximately 7% with the improved connector, before the ETT or mask. Additional aerosol losses are known to occur in the infant ETT, which can have an internal diameter as small as 2.5 mm.…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of small charged pharmaceutical aerosols in a model of a ventilated neonate

Holbrook

Hindle

Longest

2017

Journal of Aerosol Science

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Aerosolized medications may benefit infants receiving mechanical ventilation; however, the lung delivery efficiency of these aerosols is unacceptably low. In vitro experiments were conducted to evaluate aerosol delivery through conventional and modified ventilation systems to the end of a 3mm endotracheal tube (ETT) under steady state and realistic cyclic flow conditions. System modifications were employed to investigate the use of small charged particles and included streamlined components, a reduction in nebulizer liquid flow rate, synchronization with inspiration, and implementation of a previously designed low-flow induction charger (LF-IC), which was further modified in this study. Cyclic flow experiments implemented a modern ventilator with bias airflow and an inline flow meter, both of which are frequently excluded from in vitro tests but included in clinical practice. The modified LF-IC system demonstrated superior delivery efficiency to the end of the ETT (34%) compared with the commercial system (~1.3%) operating under cyclic ventilation conditions. These findings indicate that commercial systems still provide very low lung delivery efficiencies despite decades of innovation. In contrast, the modified system increased dose delivery to the end of the ETT by 26-fold. Despite initial concerns, the charged aerosol could be efficiently delivered through the small diameter ETT and reach the lungs. Future studies will be required to determine if the applied particle charge can eliminate expected high exhalation aerosol loss and will require the development of a realistic lung model.

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“…6). 72 The low-deadspace connector has 2 different paths for the gas provided by the ventilator and the aerosol. The device lacks a oneway valve system that would prevent the practitioner from having to break the circuit when the nebulizer connections are removed.…”

Section: Special Conditionsmentioning

confidence: 99%

Assessing New Technologies in Aerosol Medicine: Strengths and Limitations

Berlinski

2015

Respir Care

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Aerosols are the mainstay of treatment for pulmonary diseases such as asthma, cystic fibrosis, and COPD. In addition, aerosols are also being used for systemic drug delivery. Patients need devices that are safe, reliable, portable, and easy to use; have few steps in their operation; help them keep track of the remaining doses; are not expensive; and provide age-appropriate positive reinforcement and feedback. Computational fluid dynamics, human factor sciences, and quality by design are now applied to device development. Matching patient, drug, and device remains a challenge. Formulary restrictions, the current status of the industry-academia relationship, and the need to use multiple platforms hinder the process. Patients and families need to participate in the selection of a device that is appropriate for them. Practitioners need comparative data to help them choose the right device. New devices and drugs can be compared with the existing technology using in vitro and in vivo methods (lung imaging, pharmacokinetic and pharmacodynamics studies). Drug manufacturers need to be able to justify coverage of new products by third-party payers by showing a positive cost/benefit relationship. Finally, post-market surveillance is necessary for old drugs with new devices or for new drugs and devices to ensure patient safety.

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Aerosolized Albuterol Sulfate Delivery under Neonatal Ventilatory Conditions: In Vitro Evaluation of a Novel Ventilator Circuit Patient Interface Connector

Cited by 23 publications

References 16 publications

Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

In vitro assessment of small charged pharmaceutical aerosols in a model of a ventilated neonate

Assessing New Technologies in Aerosol Medicine: Strengths and Limitations

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