Article

Physicochemical Aspects and Efficiency of Albuterol Nebulization: Comparison of Three Aerosol Types in an In Vitro Pediatric Model

December 2014
Respiratory Care 60(1)

December 2014
60(1)

DOI:10.4187/respcare.02490

Source
PubMed

Authors:

Ermindo R. Di Paolo

Lausanne University Hospital

Markoulina Berger

Lausanne University Hospital

Show all 6 authorsHide

Advances in nebulizer design have produced both ultrasonic nebulizers and devices based on a vibrating mesh (vibrating mesh nebulizers), which are expected to enhance the efficiency of aerosol drug therapy. The aim of this study was to compare 4 different nebulizers, of 3 different types, in an in vitro model using albuterol delivery and physical characteristics as benchmarks. The following nebulizers were tested: Sidestream Disposable jet nebulizer, Multisonic Infra Control ultrasonic nebulizer, and the Aerogen Pro and Aerogen Solo vibrating mesh nebulizers. Aerosol duration, temperature, and drug solution osmolality were measured during nebulization. Albuterol delivery was measured by a high-performance liquid chromatography system with fluorometric detection. The droplet size distribution was analyzed with a laser granulometer. The ultrasonic nebulizer was the fastest device based on the duration of nebulization; the jet nebulizer was the slowest. Solution temperature decreased during nebulization when the jet nebulizer and vibrating mesh nebulizers were used, but it increased with the ultrasonic nebulizer. Osmolality was stable during nebulization with the vibrating mesh nebulizers, but increased with the jet nebulizer and ultrasonic nebulizer, indicating solvent evaporation. Albuterol delivery was 1.6 and 2.3 times higher with the ultrasonic nebulizer and vibrating mesh nebulizers devices, respectively, than with the jet nebulizer. Particle size was significantly higher with the ultrasonic nebulizer. The in vitro model was effective for comparing nebulizer types, demonstrating important differences between nebulizer types. The new devices, both the ultrasonic nebulizers and vibrating mesh nebulizers, delivered more aerosolized drug than traditional jet nebulizers. Copyright © 2014 by Daedalus Enterprises Inc.

Aerosol delivery of inhalation devices with different add-on connections to invasively ventilated COPD subjects: An in-vivo study

Article

Sep 2021
EUR J PHARM SCI

Aerosol delivery to mechanically ventilated patients requires add-on connections to place the inhalation device within the ventilation circuit. The study aimed to evaluate the performance of Combihaler in dual limb invasive mechanical ventilation (IMV). A ventilator with a humidified dual limb circuit was adjusted to volume-controlled mode to imitate the adult breathing parameters. 24 (12 females) intubated chronic obstructive pulmonary disease (COPD) subjects had undergone the study. All patients were prescribed inhaled salbutamol dose delivered by either a metered-dose inhaler (pMDI) or vibrating mesh nebulizer (VMN). Each subject received salbutamol in four different inhalation device/connection conditions; pMDI+VMN+Combihaler, VMN+Combihaler, VMN+T-piece, and pMDI+T-piece. They were individually placed in the inspiratory limb at Y-piece. 5mg salbutamol was delivered by VMN with and without 2 pMDI puffs of salbutamol (100 µg), and 500µg was delivered by pMDI+T-piece. After aerosol delivery, two urine samples were collected from the patient; 30 min post-inhalation (USAL0.5) and cumulatively 24 h post-inhalation (USAL24) as indexes of lung deposition and systemic absorption, respectively. For the ex-vivo study, a collecting filter was placed before an endotracheal tube (ETT) to collect the delivered inhalable dose. In-vitro aerodynamic characteristics were also investigated. pMDI+VMN+Combihaler delivered more salbutamol to the lung and the ex-vivo filter than VMN+T-piece (p˂0.05, p≤0.01, respectively). VMN delivered a higher salbutamol amount to the lung, systemically, and the ex-vivo filter than pMDI+T-piece (p˂0.001). pMDI+VMN+Combihaler and VMN+Combihaler delivered aerosols with a less mass median aerodynamic diameter (MMAD) and higher fine particle fraction (FPF) compared to VMN+T-piece (p≤0.01 for MMAD, p˂0.01 for FPF) and pMDI+T-piece (p˂0.01 for both MMAD and FPF). Results of the study showed that pMDI+VMN+ Combihaler delivered more salbutamol than VMN+T-piece in IMV and demonstrate that 5 puffs (500-µg) of salbutamol with pMDI+T-piece has a lower aerosol delivering power at the level of USAL0.5, USAL24, and the ex-vivo inhalable dose than 5 mg nebulized salbutamol by VMNs in IMV.

Generation and characterisation of electrostatically charged radiolabelled aerosols for lung scintigraphy

Article

Feb 2021

Particles and droplets produced from pharmaceutical inhaler devices are naturally charged. Previous in silico and in vitro studies have shown that the levels of these electrostatic charges may potentially affect deposition in the airways but this has not been confirmed in vivo. Human lung scintigraphic studies using radiolabelled particles with controlled charges would provide crucial data on locating the deposition sites with respect to the particle charge level. An aerosol charging rig has been developed for this purpose. 99mTc-radiolabelled droplets from an Aerogen® Solo vibrating mesh nebulizer were charged by induction and then dried to yield positively charged particles. Particles with near-neutral charges were produced at an induction voltage of −0.4 kV, while those with 10-4,000 elementary charges per particle were generated at −4.5 kV, depending on the particle size. The number of elementary charges per particle generally decreased with radioactivity, especially for solutions at 400 and 800 MBq/mL. This was attributed to the indirect ionizing effect of the gamma radiation in the air, which produced bipolar ions that neutralized the initially charged particles. Radioactivity at 100 MBq/mL was found to be optimal in generating the highest particle charges that could potentially affect in vivo deposition in the lungs. The aerosol charging rig is suitable for use in human scintigraphy studies which we will conduct in the near future. Copyright © 2021 American Association for Aerosol Research

Effect of different connection adapters on aerosol delivery in invasive ventilation setting; an in-vitro study

Article

Feb 2021
J DRUG DELIV SCI TEC

Introduction Different aerosol generators are used during mechanical ventilation connected to spacers or adapters. The design and volume of these connections can significantly affect aerosol delivery. This study aimed to evaluate the impact of a variety of connections on aerosol delivery in invasive mechanical ventilation (IMV) setting. Methods A ventilator was set at volume-controlled mode (Vt = 500 ml, f = 15/min, PEEP = 5 cm H20), and connected to a test lung model to simulate intubated mechanically ventilated adults with a 1:3 ratio of inspiratory to expiratory phase. An endotracheal tube of 8 mm inner diameter was used in this model, inserted between Y-piece and the breathing simulator. Ventilator settings were selected typically as those indicated for COPD patients in the intensive care unit when IMV is prescribed during acute exacerbations. Aerosol-generator was placed in dual limb IMV at Y-piece in the inspiratory limb. For nebulizer delivery; 1 ml respirable solution was nebulized using vibrating mesh nebulizer with three connection settings; I: T-piece, II: Combihaler (new and old version), and III: Combihaler with a pressurized metered-dose inhaler (pMDI). Only with connection III, two pMDI puffs, 100 μg salbutamol each, were actuated before nebulization of 1 ml of salbutamol solution. For pMDI delivery; pMDI puffs (100 μg per puff) were delivered using two connection settings I: pMDI T-piece adapter (2 and 5 pMDI salbutamol puffs), and II: Combihaler (2 pMDI salbutamol puffs only). 2 and 5 pMDI salbutamol puffs were delivered by pMDI T-piece adapter to determine the possible effect of aerosolized drug condensation on the T-piece. Fates of nebulized, and actuated-doses were determined. Results No significant difference was observed between old and new Combihalers used to deliver nebulized doses with and without pMDI. The pMDI T-piece adapter delivered significantly higher pMDI aerosol than Combihaler (p < 0.05). The new Combihaler delivered a slightly higher pMDI dose than the old Combihaler. Conclusions The antistatic property of the new Combihaler affected pMDI delivered dose similar to conventional spacer but does not affect the nebulized dose. Further clinical studies are needed to determine the bronchodilator effect of the pre-nebulization pMDI puffs on the nebulized dose.

Inducible Laryngeal Obstruction in the Paediatric Population – Review of the Literature and Current Understanding

Article

Full-text available

Jan 2018

Inducible laryngeal obstruction (ILO) is a complex entity and its exact mechanisms are still unclear. It is characterised by transient and reversible narrowing of the larynx in response to external triggers, resulting in symptoms such as cough, dyspnoea and noisy breathing. The prevalence of this condition in adult or paediatric populations is uncertain. Management of ILO starts by establishing an accurate diagnosis, and treatment includes control of trigger factors, breathing and relaxation techniques, and speech and respiratory therapy. The aim of this article is to summarise current understanding and provide a review of the literature of ILO in the paediatric population.

Vibrating Mesh Nebulisers – Can Greater Drug Delivery to the Airways and Lungs Improve Respiratory Outcomes?

Article

Full-text available

Jan 2018

Stephan Ehrmann

Aerosols are an increasingly important mode of delivery of drugs, particularly bronchodilators, for the treatment of respiratory diseases, notably asthma and chronic obstructive pulmonary disease. The most common type of nebuliser is the jet nebuliser (JN); they have been in use for more than a century but these devices can be cumbersome to use and may sometimes deliver insufficient amounts of drug. A more recent development in aerosol therapy is the vibrating mesh nebuliser (VMN) which is very user friendly and is more efficient than the JNs due to an extremely low residual volume. Scintigraphy images from studies of volunteer subjects using radio-labelled aerosol treatment show that VMN-generated aerosols deliver more drug to patients in a shorter period of time than JN-generated aerosols. Various bench, animal model and small clinical studies have shown that VMNs are more efficient than JNs in drug delivery, potentially improving clinical outcomes. These studies have included various breathing circuits used in mechanical ventilation (MV), non-invasive ventilation, high-flow nasal cannula systems and devices for spontaneously breathing patients. The efficiency of drug delivery was affected by factors including the position of the nebuliser in the circuit and humidity. Some studies have shown potential substantial savings by hospitals in the cost of MV treatments after switching from metered dose inhalers to VMNs. VMNs have also been shown to be effective for the administration of inhaled antibiotics, corticosteroids and other drugs. Larger studies of the effects of VMNs on patient outcomes are needed but they are likely to be an increasingly important means of administering therapies to a burgeoning population with respiratory disease.

Optimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA

Article

May 2023
INT J PHARMACEUT

Lipid nanoparticles (LNPs) have demonstrated efficacy and safety for mRNA vaccine administration by intramuscular injection; however, the pulmonary delivery of mRNA encapsulated LNPs remains challenging. The atomization process of LNPs will cause shear stress due to dispersed air, air jets, ultrasonication, vibrating mesh etc., leading to the agglomeration or leakage of LNPs, which can be detrimental to transcellular transport and endosomal escape. In this study, the LNP formulation, atomization methods and buffer system were optimized to maintain the LNP stability and mRNA efficiency during the atomization process. Firstly, a suitable LNP formulation for atomization was optimized based on the in vitro results, and the optimized LNP formulation was AX4, DSPC, cholesterol and DMG-PEG2K at a 35/16/46.5/2.5 (%) molar ratio. Subsequently, different atomization methods were compared to find the most suitable method to deliver mRNA-LNP solution. Soft mist inhaler (SMI) was found to be the best for pulmonary delivery of mRNA encapsulated LNPs. The physico-chemical properties such as size and entrapment efficiency (EE) of the LNPs were further improved by adjusting the buffer system with trehalose. Lastly, the in vivo fluorescence imaging of mice demonstrated that SMI with proper LNPs design and buffer system hold promise for inhaled mRNA-LNP therapies.

Not all nebulizers are created equal: Considerations in choosing a nebulizer for aerosol delivery during mechanical ventilation

Article

Full-text available

Feb 2023

Introduction Aerosol therapy is commonly prescribed in the mechanically ventilated patient. Jet nebulizers (JN) and Vibrating Mesh Nebulizers (VMN) are the most common nebulizer types, however, despite VMN’s well established superior performance, JN use remains the most commonly used of the two. In this review we describe the key differentiators between nebulizer types and how considered selection of nebulizer type may enable successful therapy and the optimisation of drug/device combination products. Areas covered Following a review of the published literature up to February 2023, the current state of the art in relation to JN and VMN is discussed under the headings of in vitro performance of nebulizers during mechanical ventilation, respective compatibility with formulations for inhalation, clinical trials making use of VMN during mechanical ventilation, distribution of nebulised aerosol throughout the lung, measuring the respective performance of nebulizers in the patient and non-drug delivery considerations in nebulizer choice. Expert opinion Whether for standard care, or the development of drug/device combination products, the choice of nebulizer type should not be made without consideration of the unique needs of the combination of each of drug, disease and patient types, as well as target site for deposition, and healthcare professional and patient safety.

Optimal delivery of aerosolized medication to mechanically ventilated pediatric and neonatal patients: A scoping review

Article

Full-text available

Dec 2022

Objectives: Delivering aerosolized medication to patients during mechanical ventilation is a common practice in respiratory therapy for adult, pediatric, and neonatal populations. However, aerosol delivery in pediatric populations is inconsistent and challenging, impacting how the drug is delivered. Some factors that influence drug delivery efficiency are directly under the purview of the clinician or therapist administering the drugs. However, excessive variability exists amongst clinicians and therapists working at the same site and between different sites. This review aims to systematically summarize the literature to identify current practice variations, identify common practices, and provide suggestions to guide future research in this area. In addition, this scoping review aims to identify the available evidence and knowledge gaps in the literature regarding the delivery of aerosolized medication to pediatric populations during mechanical ventilation. More specifically, the question that guided our research was: What are the best strategies for optimizing aerosol delivery of medication to pediatric patients, including neonates, while on mechanical ventilation? Methods: A scoping review, using the Joanna Briggs Institute methodology, was conducted until September 2022 in the CINAHL, EMBASE (Ovid), and Medline (Ovid) databases. Our initial search yielded 248 articles. After screening the titles, abstracts, and full text of the articles according to inclusion and exclusion criteria, five articles were analyzed. Results: We identified three main topics for discussion: the type of device used for administering aerosolized medication, appropriate mechanical ventilation settings, and optimal placement of the nebulizer delivery system. Conclusion: Of the three topics we intended to discuss, we only found enough evidence to suggest using mesh nebulizers to increase aerosol deposition. We found conflicting or outdated results for the other two topics. This demonstrates a significant gap in the literature since aerosol medications are routinely administered to mechanically ventilated neonatal and other pediatric patients.

Inhaled IgG1 antibodies: The buffering system is an important driver of stability during mesh-nebulization

Article

Nov 2022
EUR J PHARM BIOPHARM

In the past decade, oral inhalation has been a thriving focus of research to administer antibody directly to the lungs as an aerosol, for local treatment of respiratory diseases. Formulation of inhaled antibodies is central for the stability of antibody, lung safety and to ensure inhaler performances. Surfactants have already been shown to prevent antibody degradation during aerosolization, but little is known about the impact of other components of liquid formulations on the structural stability of antibodies. Here, we report for the first time to the best of our knowledge, a significant effect of the buffering system on monoclonal antibodies stability, during mesh-nebulization. While the monoclonal antibody extensively aggregated in citrate buffer after nebulization and required high concentration of polysorbate 80 (PS80) to maintain protein integrity, acetate and histidine buffers resulted in a slight to moderate aggregation without PS80 and low concentration of PS80 was sufficient to stabilize antibody during mesh-nebulization.

Bronchodilator response after two methods of salbutamol nebulization in asthmatic children

Article

Full-text available

Jun 2022
POSTEP DERM ALERGOL

Introduction: Salbutamol is used in bronchodilator response testing (BDRT), which is an important diagnostic tool in bronchial obstructive diseases. Most available studies compare the bronchodilator response of salbutamol administered with a pressurized metered-dose inhaler and salbutamol in a nebulization solution. Aim: The spirometric evaluation of the bronchodilator response of two methods of salbutamol nebulization in asthmatic children. Material and methods: A randomized, open, comparative study was conducted in which 132 children with partially controlled asthma and current bronchial obstruction determined by spirometry were enrolled. BDRT was conducted using salbutamol solution administered with either a continuous jet nebulizer (CON) or a breath-actuated jet nebulizer (BAN). The BAN group received half the dose of the drug compared to the CON group, i.e. 2.5 mg. Changes in FEV1 and FEF25-75 after drug administration were calculated in relation to the baseline values. Results: The change in FEV1 after salbutamol administration was 16.9 ±9.7% in the BAN group and was statistically significantly higher than in the CON group (12.6 ±8.8%) (p = 0.026). The change in FEF25-75 was 37.7 ±23.2% in the BAN group and 32.7 ±25.5% in the CON group (p = 0.061). There were no statistically significant differences in the frequency of adverse events between the compared groups. Conclusions: Salbutamol inhaled from BAN results in a better bronchodilator response than twice the nominal dose of this drug inhaled from CON, which is due to the absence of drug loss during the expiratory phase and therefore greater pulmonary deposition.

Continuous infusion aerosol delivery of prostacyclins during mechanical ventilation: Challenges, limitations, and recent advances

Article

Full-text available

Apr 2022

Introduction: Critically ill mechanically ventilated patients routinely receive aerosol delivery of the short-acting agent prostacyclin, epoprostenol, by continuous infusion via nebulizer and syringe pump. This procedure is "off-label" as no FDA approved drug presently exists. Without standardized protocols, therapy is based on prior experience with bronchodilators, limited studies of delivery systems and anecdotal clinical trials. Current protocols based upon patient body weight and drug concentration determines the infusion rate of drug dose delivered to the nebulizer by the pump, which is only distantly related to dose delivered to the lung and may be altered by many factors. Areas covered: This paper reviews the background of this technique as well as current methods of managing drug delivery, technical challenges, and limitations. A recent advance in aerosol laboratory bench testing, using radiolabeled aerosols, is presented to reveal important factors defining delivery. Expert opinion: Off-label use of continuously nebulized prostacyclin in the ICU lacks the support of large clinical trials needed for FDA clearance. However, comprehensive bench studies afford the potential for clinicians to better understand and manage therapy at a level above simple dosing of the nebulizer by body weight. New research techniques are enhancing our basic comprehension of the interaction between aerosol devices and the mechanical ventilator.

Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study

Article

Full-text available

Mar 2022

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.

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

Article

May 2022
EXP LUNG RES

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.

Effect of Vibrating Mesh Nebulizer Aerosol Technology on the In Vitro Activity of Ribavirin Against Respiratory Syncytial Virus

Article

Sep 2021

Background: Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select patients and the severely ill. The vibrating mesh nebulizer was previously demonstrated to be an effective alternative to the small-particle aerosol generator in particle size, chemical makeup, and concentrations of the ribavirin before and after nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin's activity before and after nebulization via vibrating mesh nebulizer. Methods: We grew and infected human epithelial type 2 cells and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. Results: Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. Conclusions: The vibrating mesh nebulizer did not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the vibrating mesh nebulizer in the administration of inhaled ribavirin.

TERAPIA INHALATORIA EN PACIENTES QUE RECIBEN VENTILACIÓN MECÁNICA

Article

Full-text available

Jan 2021

Fernando Íñiguez O

Se discuten los factores que influyen en la terapia inhalatoria, tanto en general como específicamente para pacientes ventilados, discutiendo los aspectos físicos, los generadores de aerosol y ciertos dispositivos disponibles para su aplicación. Se proponen recomendaciones necesarias para aumentar la fracción de depósito pulmonar y mejorar la eficiencia y seguridad de la terapia inhalatoria en niños que reciben soporte respiratorio.

Self-contained system for mitigation of contaminated aerosol sources of SARS-CoV-2

Preprint

Full-text available

Feb 2021

Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing ¹⁻³ and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected, ⁴ eliminating transmissions from infection sources is also important to prevent disease transmission. Supportive therapies for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pneumonia such as oxygen supplementation, nebulizers and non-invasive mechanical ventilation all carry an increased risk for viral transmission via aerosol to healthcare workers. ⁵⁻⁹ In this work, we study the efficacy of five methods for self-containing aerosols emitted from infected subjects undergoing nebulization therapies with a diverse spectrum on oxygen delivery therapies. The work includes five study cases: Case I: Use of a Full-Face Mask with biofilter in bilevel positive airway pressure device (BPAP) therapy, Case II: Use of surgical mask in High Flow Nasal Cannula (HFNC) therapy, Case III: Use of a modified silicone disposable mask in a HFNC therapy, Case IV: Use of a modified silicone disposable mask with a regular nebulizer and normal breathing, Case V: Use of a mitigation box with biofilter in a Non-Invasive Positive Pressure Ventilator (NIPPV). We demonstrate that while cases I, III and IV showed efficacies of 98-100%; cases II and V , which are the most commonly used, resulted with significantly lower efficacies of 10-24% to mitigate the dispersion of nebulization aerosols. Therefore, implementing cases I, III and IV in health care facilities may help battle the contaminations and infections via aerosol transmission during a pandemic.

Comparison of pulmonary deposition of nebulized technetium‐diethylenetriamine‐pentaacetic acid through 3 inhalation devices in healthy dogs

Article

Full-text available

Feb 2021
J VET INTERN MED

Background Inhalation treatment frequently is used in dogs and cats with chronic respiratory disease. Little is known however about the performance of delivery devices and the distribution of aerosolized drugs in the lower airways. Objective To assess the performance of 3 delivery devices and the impact of variable durations of inhalation on the pulmonary and extrapulmonary deposition of nebulized 99mtechnetium‐diethylenetriamine‐pentaacetic acid (99mTc‐DTPA). Animals Ten university‐owned healthy Beagle dogs. Methods Prospective crossover study. Dogs inhaled the radiopharmaceutical for 5 minutes either through the Aerodawg spacer with a custom‐made nose‐muzzle mask, the Aerochamber spacer with the same mask, or the Aerodawg spacer with its original nose mask. In addition, dogs inhaled for 1 and 3 minutes through the second device. Images were obtained by 2‐dimensional planar scintigraphy. Radiopharmaceutical uptake was calculated as an absolute value and as a fraction of the registered dose in the whole body. Results Mean (±SD) lung deposition for the 3 devices was 9.2% (±5.0), 11.4% (±4.9), and 9.3% (±4.6), respectively. Differences were not statistically significant. Uptake in pulmonary and extrapulmonary tissues was significantly lower after 1‐minute nebulization, but the mean pulmonary/extrapulmonary deposition ratio (0.38 ± 0.27) was significantly higher than after 5‐minute nebulization (0.16 ± 0.1; P = .03). No significant differences were detected after 3‐ and 5‐minute nebulization. Conclusion and Clinical Importance The performance of a pediatric spacer with a custom‐made mask is comparable to that of a veterinary device. One‐minute nebulization provides lower pulmonary uptake but achieves a better pulmonary/extrapulmonary deposition ratio than does 5‐minute nebulization.

Droplet Size and Distribution of Nebulized 3% NaCl, Albuterol, and Epoprostenol by Phase Doppler Particle Analyzer

Article

Full-text available

Feb 2021
CURR THER RES CLIN E

Purpose : Aerosolized drug therapy administered to mechanically ventilated patients is a standard part of pulmonary critical care medicine. Aerosol particle size and distribution are important factors in the optimal delivery of aerosolized drugs to ventilated patients. The objective of this study was to characterize aerosol droplet size and distribution with laser diffraction for nebulized 3% sodium chloride (NaCl), albuterol, and epoprostenol sodium (containing glycine) delivered via Aerogen Aeroneb Solo Mesh Nebulizers. Methods : A series of functional flow tests were run on each of 8 Solo mesh nebulizers prior to the study to verify accuracy of flow rates in mL/minute. Aerosolized droplets exiting the nebulizer heads were then measured using a phase Doppler particle analyzer. Data collected during delivery of 3% NaCl, albuterol, and epoprostenol sodium included aerosol droplet size distribution, mass median aerodynamic diameter (MMAD), and geometric standard deviation. For each Solo nebulizer, droplet size measurements were taken 2 cm away from the nebulizer head and 2 cm away from the wye of a heated, humidified adult ventilator circuit. For measurements taken at the wye, 4 distinct, continuous flow rates (2, 10, 20, and 40 L/min) were generated by an air pump to simulate inspiratory flows delivered with mechanical ventilation. The expiratory limb was capped, and the nebulizer head was inserted into the breathing circuit upstream of the humidifier. Findings : Each Solo nebulizer met Aerogen's recommended minimum flow rate of 0.2 mL/min, ranging from 0.23 to 0.31 mL/min. The MMAD of the 3 tested aerosols was several times smaller when measured at the wye outlet of the heated/humidified breathing circuit (0.82–2.73 μm) compared with droplets measured directly at the nebulizer outlet (MMAD, 4.6–7.3 µm). There was also significant variability across Solo heads with some ventilator flow rates. The mean MMAD at the wye for the 3% NaCl solution, albuterol, and epoprostenol test solutions was 1.62 µm, 1.09 µm, and 1.18 µm, respectively. The mean MMAD at the nebulizer for the 3% NaCl solution, albuterol, and epoprostenol test solutions was 5.37 µm, 5.73 µm, and 6.73 µm, respectively. Implications : Results from this study suggest that particle size of aerosolized drugs administered via a commonly used setup for delivery of in-line aerosols to mechanically ventilated patients may be several times smaller than expected and may result in less drug being delivered to the patient than previously realized.

Aerosol Delivery of Dornase Alfa Generated by Jet and Mesh Nebulizers

Article

Full-text available

Jul 2020

Recent reports on mesh nebulizers suggest the possibility of stable nebulization of various therapeutic protein drugs. In this study, the in vitro performance and drug stability of jet and mesh nebulizers were examined for dornase alfa and compared with respect to their lung delivery efficiency in BALB/c mice. We compared four nebulizers: two jet nebulizers (PARI BOY SX with red and blue nozzles), a static mesh nebulizer (NE-U150), and a vibrating mesh nebulizer (NE-SM1). The enzymatic activity of dornase alfa was assessed using a kinetic fluorometric DNase activity assay. Both jet nebulizers had large residual volumes between 24% and 27%, while the volume of the NE-SM1 nebulizer was less than 2%. Evaluation of dornase alfa aerosols produced by the four nebulizers showed no overall loss of enzymatic activity or protein content and no increase in aggregation or degradation. The amount of dornase alfa delivered to the lungs was highest for the PARI BOY SX-red jet nebulizer. This result confirmed that aerosol droplet size is an important factor in determining the efficiency of dornase alfa delivery to the lungs. Further clinical studies and analysis are required before any conclusions can be drawn regarding the clinical safety and efficacy of these nebulizers.

Clinical Efficacy of Vibrating Mesh and Jet Nebulizers With Different Interfaces in Pediatric Subjects With Asthma

Article

Mar 2020

BACKGROUND: Nebulizers are commonly used in emergency departments to deliver bronchodilators to children with asthma exacerbations. However, no clinical study comparing a vibrating mesh nebulizer with a jet nebulizer is available in this patient population. The purpose of this study was to compare the clinical efficacy of a vibrating mesh nebulizer to a jet nebulizer combined with a mouthpiece or mask in children with asthma exacerbations admitted to the emergency department. METHODS: We conducted a single-blinded randomized clinical trial of 217 children (2–18 y old) with a moderate to severe asthma exacerbation in the emergency department. Assessment of severity was defined by our acute asthma score, adapted from the Pediatric Asthma Score. Subjects were randomized to receive bronchodilator treatment via vibrating mesh nebulizer (n = 108) or jet nebulizer (n = 109) and were treated until they achieved a mild asthma score and were discharged or until a decision to admit was made. All subjects were treated per our acute asthma clinical pathway algorithm for the emergency department with modifications to allow for blinding, assessment of treatment, and data collection. Outcome variables included hospital admission rate, number of treatments, and time to mild asthma score. RESULTS: There was a significant difference in baseline asthma score between subjects treated with the vibrating mesh nebulizer and those treated with the jet nebulizer (P = .042), but no other significant differences in demographics existed between groups. To adjust for effect of baseline asthma score, a multiple logistic regression model was used to model admission. The vibrating mesh nebulizer group had a lower probability of being admitted to the hospital (P = .062), and they required significantly fewer treatments (P < .001) and less time to reach a mild asthma score (P = .004) than those in the jet nebulizer group. In subjects with a mask interface, the vibrating mesh nebulizer significantly reduced the probability of admission (P = .032). CONCLUSIONS: Subjects treated with a vibrating mesh nebulizer required significantly fewer treatments and less time to achieve a mild asthma score. In subjects with a mask interface, the vibrating mesh nebulizer significantly reduced the probability of admission compared to jet nebulizer. (ClinicalTrials.gov registration NCT02774941.) Key words: aerosols; jet nebulizer; vibrating mesh nebulizers; pediatric asthma; moderate; severe; children; emergency department; albuterol. [Respir Care 0;0(0):1–_. © 0 Daedalus Enterprises]

Terapia inhalatoria en pacientes que reciben ventilacion mecanica

Article

Full-text available

Oct 2018

Fernando Iñiguez Osmer

149 Terapia inhalatoria en pacientes que reciben ventilación mecánica TERAPIA INHALATORIA EN PACIENTES QUE RECIBEN VENTILACIÓN MECÁNICA INHALATION THERAPY IN PATIENTS WITH MECHANICAL VENTILATION ABSTRACT We discuss the general as well as the specific factors influencing this therapy among patients on mechanical ventilation, describing its physical aspects, aerosol generators and some devices available for their application. Recommendations are proposed to increase lung deposition and improve the efficiency and safety of inhalation therapy in children receiving respiratory support. RESUMEN Se discuten los factores que influyen en la terapia inhalatoria, tanto en general como específicamente para pacientes ventilados, discutiendo los aspectos físicos, los generadores de aerosol y ciertos dispositivos disponibles para su aplicación. Se proponen recomendaciones necesarias para aumentar la fracción de depósito pulmonar y mejorar la eficiencia y seguridad de la terapia inhalatoria en niños que reciben soporte respiratorio. INTRODUCCIÓN Los pacientes que reciben soporte ventilatorio en el hospital, tanto por condiciones agudas o crónicas, con frecuencia requieren la administración de medicamentos en forma de aerosol. También puede ser necesaria la terapia inhalatoria en pacientes que reciben asistencia ventilatoria en domicilio. Esta terapia puede utilizar un Inhalador de Dosis Medida presurizado (IDMp) o bien un nebulizador, junto a los dispositivos que permitan la administración del aerosol en el circuito de ventilación. La terapia con aerosoles constituye una ciencia y un arte. La ciencia incluye a la farmacología, anatomía y fisiología cardiopulmonar, además de principios físicos, químicos y matemáticos, ya que la entrega adecuada del medicamento al sitio de acción en la Vía Aérea (VA) depende de la técnica utilizada. Es aquí donde el arte interviene, seleccionando el dispositivo más adecuado para el paciente, considerando su edad, diagnóstico, equipos disponibles y modalidad ventilatoria (1). A continuación se revisarán algunos aspectos relacionados con las características de los aerosoles, que es necesario conocer para comprender mejor los fenómenos y variables que influyen sobre el depósito pulmonar de las partículas de un aerosol. El conocimiento de esta área le permitirá al clínico poder tomar decisiones más racionales cuando decide entregar un aerosol a la VA de un paciente con soporte respiratorio. CARACTERÍSTICAS FÍSICAS DE UN AEROSOL Definición Un aerosol es la suspensión de partículas líquidas o sólidas en un medio gaseoso. La terapia inhalatoria corresponde a la administración de un aerosol a un paciente con fines terapéuticos. Tamaño de la partícula y masa El tamaño de las partículas es una característica física muy importante al considerar la eficiencia en el depósito pulmonar de un aerosol. El Diámetro Aerodinámico (dae) es, por definición, el diámetro de una esfera con densidad uno (ρ = 1), que posee la misma velocidad terminal de depósito que la partícula en consideración. Al considerar las características de la partícula, esta variable independiente puede correlacionar el efecto del diámetro geométrico y la densidad de la partícula, como se describe en la ecuación 1, con partículas mayores a 1 μm, donde d corresponde al diámetro real de la esfera, ρ a la densidad de la partícula y ρ0 a la densidad uno (del agua). Expresado en forma más simple, el dae corresponde al producto del diámetro de la partícula multiplicado por la raíz cuadrada de la densidad de la partícula. El Diámetro Aerodinámico Medio de la Masa (DAMM) corresponde a un tamaño de partícula (en micrones) que divide a la masa, de tal modo que la mitad de las partículas de ese aerosol tienen un diámetro mayor y la otra mitad un diámetro ARTÍCULOS ORIGINALES / ORIGINAL ARTICLES Ecuación 1. dae = d. ρ ρ0

Effect of Nebulizer Location and Spontaneous Breathing on Aerosol Delivery During Airway Pressure Release Ventilation in Bench Testing

Article

Full-text available

Sep 2018

Background: Airway pressure release ventilation (APRV) maintains a sustained airway pressure over a large proportion of the respiratory cycle, and has a long inspiratory time at high pressure. The purpose of this study was to determine the influence of the APRV with and without spontaneous breathing on albuterol aerosol delivery with a continuous vibrating-mesh nebulizer (VMN) placed at different positions on an adult lung model of invasive mechanical ventilation. Methods: An adult lung model was assembled by connecting a ventilator with a dual-limb circuit to an 8-mm inner diameter endotracheal tube (ETT) and collecting filter attached to a test lung with set compliance of 0.1 L/cmH2O and resistance of 0.5 cmH2O/(L·s). Four ventilator modes were compared: pressure control ventilation (PCV) with no bias flow, PCV with bias flow of 6 L/min (PCVBF6), APRV with no spontaneous breaths (APRV), and APRV with spontaneous breath trigger (APRVs). Peak inspiratory pressure, peak end-expiratory pressure, aerosol dose, and nebulization time were similar for all modes. The VMN was placed (1) between Y-piece and inspiratory limb, (2) at the gas outlet of a heated humidifier, and (3) at the gas inlet of a heated humidifier. Albuterol sulfate (5 mg/2.5 mL) was administered with each run and collected on a filter distal to the ETT. Deposited drug was eluted from each filter (purified water) and analyzed by UV spectrophotometry at 276 nm. Analysis of variance [general linear model (GLM) multivariate] was performed using the linear model of multiple variables, significance at p < 0.05. Results: Albuterol (in micrograms, mean ± standard deviation) delivered was higher with VMN placed at the gas inlet of the humidifier with each mode of ventilation (p < 0.01). APRVs has the highest albuterol delivery followed by PCV, PCVBF6, and APRV (1706.2 ± 60.9 μg vs. 1490.6 ± 61.1 μg vs. 1182.3 ± 61.4 μg vs. 1153.1 ± 99.7 μg, respectively, p < 0.001). The minute volume was positively correlated with the inhaled albuterol dose. Conclusions: Spontaneous breathing increased the albuterol delivery during APRV, compared with APRV alone and PCV modes. Placing the nebulizer proximal to the ventilator was more efficient for all modes tested.

Performance of Large Spacer Versus Nebulizer T-Piece in Single-Limb Noninvasive Ventilation

Article

Nov 2018

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 g 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 g 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 pren-ebulization 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.

Anti-Tuberculosis Bacteriophage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler

Article

Full-text available

Oct 2017
PHARM RES-DORDR

Purpose: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. Methods: Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer. Results: Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x10(8) ± 0.8x10(8) pfu/min) than for the jet nebulizer (5.4x10(4) ± 1.3x10(4) pfu/min). The soft mist inhaler delivered 4.6x10(6) ± 2.0x10(6) pfu per 11.6 ± 1.6 μL ex-actuator dose. Conclusions: Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.

Is Combihaler usable for aerosol delivery in single limb non-invasive mechanical ventilation?

Article

Jun 2017
J DRUG DELIV SCI TEC

Combihaler could connect both pressurized-metered-dose-inhaler (pMDI) and nebulizers to non-invasive-ventilation-circuit (NIV). This can be used to give the patient preliminary-bronchodilator-dose in an attempt to increase forced-expiratory-volume-in-one-second (FEV1) before nebulization. It was proven effective in dual-limb-ventilation. The aim of this study was to compare aerosol-delivery by Aerogen-Solo-vibrating-mesh-nebulizer (SOLO) using its standard-T-piece and Combihaler with and without pMDI in single-limb-NIV. Each device was placed in single-limb-NIV proximal to breathing-simulator set at 15breaths.min-1, Tidal-volume=500mL and 1:3 inspiratory-expiratory-ratio. 2ml respirable-solution containing 10000μg-salbutamol was nebulized using SOLO with three connection-setting; I:T-piece, II:Combihaler and III:Combihaler-with-pMDI. Only with connection-III, two pMDI-doses, containing 100μg-salbutamol each, were actuated before nebulization of 2ml of salbutamol-solution. Fate of nebulized-dose and aerodynamic-characteristics were determined. Percentages of nominal-dose of total-inhalable-dose (TID) of both Combihaler-connections (II&III) were slightly greater than those of T-piece. Combihaler with pMDI (connection-III) had significantly-greater fine-particle-dose (FPD) and mass-median-aerodynamic-diameter (MMAD) than both T-piece and Combihaler with p-value=0.008 and 0.010, respectively for FPD and p-values=0.004 and 0.025, respectively for MMAD. Similar to dual-limb-ventilation, Combihaler work efficiently for aerosol-delivery in single-limb-NIV. The relatively higher FPD of Combihaler suggests that having large-volume-spacer in single-limb-NIV could save some aerosol from condensation. Also, combining nebulizer-with-pMDI on the same connection may provide great clinical-benefits through pre-bronchodilation.

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers

Article

Apr 2017
PEDIATR CRIT CARE ME

Objectives: To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare differences in fine particle fraction, and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a face mask, conventional, and high-frequency ventilation between Tyvaso Inhalation System and with different nebulizer locations between Tyvaso Inhalation System and vibrating mesh nebulizer. Design: Fine particle fraction was first determined via impaction with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test lung configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an endotracheal tube during conventional ventilation and high-frequency oscillator ventilator. Inhaled treprostinil was then nebulized with both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter was analyzed via high-performance liquid chromatography. Testing was done in triplicate. Independent two-sample t tests were used to compare mean fine particle fraction and inhaled mass between devices. Analysis of variance with Tukey post hoc tests were used to compare within device differences. Setting: Academic children's hospital aerosol research laboratory. Measurements and main results: Fine particle fraction was not different between the Tyvaso Inhalation System and vibrating mesh nebulizer (0.78 ± 0.04 vs 0.77 ± 0.08, respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated model and condition. When using the vibrating mesh nebulizer, delivery was highest when using high-frequency oscillator ventilator in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. Conclusions: The vibrating mesh nebulizer is a suitable alternative to the Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle fraction is similar between devices, and vibrating mesh nebulizer delivery meets or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and children during high-frequency oscillator ventilator with the vibrating mesh nebulizer may result in higher than expected dosages.

Reliability of Vibrating Mesh Technology

Article

Full-text available

Nov 2016

Background: For delivery of inhaled aerosols, vibrating mesh systems are more efficient than jet nebulizers are and do not require added gas flow. We assessed the reliability of a vibrating mesh nebulizer (Aerogen Solo, Aerogen Ltd, Galway Ireland) suitable for use in mechanical ventilation. Methods: An initial observational study was performed with 6 nebulizers to determine run time and efficiency using normal saline and distilled water. Nebulizers were run until cessation of aerosol production was noted, with residual volume and run time recorded. Three controllers were used to assess the impact of the controller on nebulizer function. Following the observational study, a more detailed experimental protocol was performed using 20 nebulizers. For this analysis, 2 controllers were used, and time to cessation of aerosol production was noted. Gravimetric techniques were used to measure residual volume. Total nebulization time and residual volume were recorded. Failure was defined as premature cessation of aerosol production represented by residual volume of > 10% of the nebulizer charge. Results: In the initial observational protocol, an unexpected sporadic failure rate was noted of 25% in 55 experimental runs. In the experimental protocol, a failure rate was noted of 30% in 40 experimental runs. Failed runs in the experimental protocol exhibited a wide range of retained volume averaging ± SD 36 ± 21.3% compared with 3.2 ± 1.5% (P = .001) in successful runs. Small but significant differences existed in nebulization time between controllers. Conclusions: Aerogen Solo nebulization was often randomly interrupted with a wide range of retained volumes.

Characterization of Ribavirin Aerosol With Small Particle Aerosol Generator and Vibrating Mesh Micropump Aerosol Technologies

Article

Full-text available

Mar 2016

Background: Ribavirin is an antiviral drug that can be administered by inhalation. Despite advancements in the oral delivery of this medication, there has been a renewed interested in delivering ribavirin via the pulmonary system. Although data are not conclusive that inhaled ribavirin improves outcomes, we set out to determine whether delivery by a newer generation nebulizer, the vibrating mesh micropump, was as effective as the recommended small-particle aerosol generator system. Methods: We compared the physicochemical makeup and concentrations of ribavirin before and after nebulization with 0.9% NaCl and sterile water. An Andersen cascade impactor was used to determine particle size distribution and mass median aerodynamic diameter, and an absolute filter was used to measure total aerosol emitted output and inhaled dose during mechanical ventilation and spontaneous breathing. Ribavirin was analyzed and quantified using high-performance liquid chromatography with tandem mass spectrometric detection. Results: Ribavirin was found to be stable in both 0.9% aqueous NaCl and sterile water with an r(2) value of 0.96 and identical coefficients of variation with no difference in drug concentration before and after nebulization with the vibrating mesh micropump. The small-particle aerosol generator produced a smaller mass median aerodynamic diameter (1.84 μm) than the vibrating mesh micropump (3.63 μm, P = .02); however, there was no significant difference in the proportion of drug mass in the 0.7-4.7-μm particle range. Total drug delivery was similar with the small-particle aerosol generator and vibrating mesh micropump in both spontaneously breathing (P = .77) and mechanical ventilation (P = .48) models. Conclusions: The vibrating mesh micropump nebulizer may provide an effective alternative to the small-particle aerosol generator in administration of ribavirin using NaCl or sterile water, both on and off the ventilator. Further clinical studies are needed to compare efficacy.

Systematic Review of Inhaled Bronchodilator and Corticosteroid Therapies in Infants with Bronchopulmonary Dysplasia: Implications and Future Directions

Article

Full-text available

Feb 2016
PLOS ONE

Background: There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD). Objective: The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes. Methods: The databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD. Results: Of 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26-30) weeks, weighted birth weight (BW) of 974(843-1310) grams, weighted post menstrual age (PMA) of 34.8(28-39) weeks, and weighted age of 53(15-86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26-29) weeks, weighted BW of 853(760-1114) grams, weighted PMA of 27.0(26-31) weeks, and weighted age of 6(0-45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27-29) weeks, weighted BW of 1057(898-1247) grams, weighted PMA of 30.7(29-45) weeks, and age 20(10-111) days old at time of evaluation). Conclusion: Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery methods as compared to traditional methods across all modalities of respiratory support, in addition to the assessment of long-term outcomes of initial responders.

Nebulised delivery of RNA formulations to the lungs: From aerosol to cytosol

Article

Dec 2023

Comparison of clinical outcomes following delivery of budesonide by both vibrating mesh nebulizer and jet nebulizer in premature infants with bronchopulmonary dysplasia

Article

Full-text available

Nov 2023

Background This study aimed to compare the efficacy of budesonide inhalation suspension administered via a vibrating mesh nebulizer vs. a jet nebulizer in the treatment of premature infants with bronchopulmonary dysplasia (BPD) undergoing high-frequency oscillatory ventilation (HFOV). Methods Between July 2020 and July 2022, we retrospectively analyzed the medical records of 36 preterm infants diagnosed with BPD who underwent HFOV. Based on the nebulizer type used, infants were categorized into the vibrating mesh nebulizer group (VMN group) or the jet nebulizer group (JN group). Post-nebulization outcomes, such as the duration of mechanical ventilation, length of stay in the neonatal intensive care unit (NICU), ventilator-associated parameters, and arterial blood gas metrics, were compared between the two groups. Treatment-associated complications were also documented. Results No significant differences were noted between the VMN and JN groups in terms of mechanical ventilation duration ( p = 0.519), NICU length of stay ( p = 0.112), ventilator-associated parameters, or complications ( p = 0.700). However, after 2 weeks of treatment, the oxygenation index ( p = 0.012) and arterial partial pressure of carbon dioxide ( p = 0.006) were more favorable in the VMN group compared to the JN group. Conclusion Among premature infants with BPD on HFOV, for administration of budesonide inhalation suspension resulted in an improved oxygenation index and reduced arterial partial pressure of carbon dioxide when compared to a jet nebulizer, indicating superior therapeutic efficacy.

Indian Guidelines on Nebulization Therapy

Article

Full-text available

Jul 2022
Indian J Tubercul

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for this purpose, and the widening scope of this therapy, even beyond the lungs; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection and other adverse outcomes. Thus, it is imperative to have a national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in nebulization practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997, and have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in acute, in-patient, out-patient and domiciliary settings in India, to address many other related issues, and to standardize nebulization practices, National College of Chest Physicians (India), constituted a National task force consisting of eminent experts in the field of Pulmonary Medicine, from different backgrounds and different parts of the country, to review the available evidence from medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines for it. This guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies/position papers/consensus reports/recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts (advisors, chairpersons, convenor and members), and as such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions based on the existing knowledge, followed by point-wise evidence statements and recommendations have been provided.

In Vitro Evaluation of Aerosol Delivery by Hand-Held Mesh Nebulizers in an Adult Spontaneous Breathing Lung Model

Article

Oct 2021

Background: Drug inhalation is common mode of treatment for chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the efficiency of aerosol devices in a simulated COPD adult lung model using five commercially available hand-held mesh nebulizers. Materials and Methods: Five nebulizers (PARI VELOX®, Omron NE-U22, Aeroneb® Go, APEX PY001, and Pocket Air®) were tested with a unit dose of 5.0 mg/2.5 mL salbutamol. An in vitro lung model (compliance: 0.06 L/cm H2O, resistance: 20 cm H2O/L/sec) was constructed to simulate parameters (tidal volume of 500 mL, respiratory rate of 15 breaths/min, inspiratory time of 1 second) of an adult patient with COPD. A bacterial filter was attached at the bronchi level for drug collection, referring as inhaled mass. After nebulization, the inhaled mass (%), dose remaining on each component (%), particle size characteristics, and nebulizer performances were analyzed. Particle size characteristics were analyzed using an 8-stage Anderson Cascade Impactor. The salbutamol particles deposited were eluted and analyzed using a spectrophotometer at 276 nm. The inhaled mass (%), dose remaining on each component (%), particle size distribution, and nebulizer performance were statistically analyzed using analysis of variance (ANOVA) with Sheffee post hoc tests. Results: Pocket Air and APEX PY001 showed the greatest inhaled mass and the lowest dose in the mouthpiece connection. The largest and smallest mass median aerodynamic diameters were found with Omron NE-U22 and PARI VELOX, respectively. In addition, the output rate and inhaled aerosol rate (IAR) of PARI VELOX were higher than those of other nebulizers. Conclusions: This study showed that the performance of commercially available mesh nebulizers varied. Aerosol particles deposited on different auxiliary equipment directly influenced the output rate and IAR of the mesh nebulizer. Clinical validation of the drug IAR is necessary to avoid overdose and reduce drug wastage.

Efficiency of Budesonide Delivery Via a Mesh Nebulizer in An In‐Vitro Neonatal Ventilator Model

Article

Jun 2020

Objective To determine the delivery efficiency of budesonide aerosol via a mesh nebulizer in a neonatal ventilator model. Design/Method In an in‐vitro ventilated neonatal model, budesonide suspension was administered using a mesh nebulizer. A collection filter was placed distal to the endotracheal tube and budesonide captured by the filter was measured using UV spectroscopy. The ventilator was, in turn, either on high frequency or conventional ventilation mode and the nebulizer was placed either proximal (close to the endotracheal tube) or distal (between the wet side of humidifier and the inspiratory circuit). Each combination (nebulizer position and ventilation mode) to assess budesonide delivery was tested five times. Results Overall delivery of budesonide to the distal end of the endotracheal tube a small percentage of the total dose administered. The deposition with conventional ventilation was 2.12% (±1.06) and 1.26% ((±0.27), with proximal and distal placement of the nebulizer, respectively. With high frequency ventilation, the deposition percentages were 1.82% ((±0.82) and 1.69% (±0.23), with proximal and distal nebulizer placement, respectively. Conclusion Only a small percentage of administered budesonide is delivered to the distal endotracheal tube, irrespective of ventilation mode and nebulizer placement. This article is protected by copyright. All rights reserved.

Aerosol Delivery to a Critically Ill Patient: A Big Issue Easily Solved by Developing Guidelines

Article

Full-text available

Jul 2018

Mohamed Abdelrahim

Nowadays, therapeutic aerosols are commonly delivered to mechanically ventilated patients by nebulizers and pressurized metered dose inhaler attached to an adapter or a spacer. Studies with asthmatics and chronic obstructive pulmonary disease patients have confirmed that aerosol delivery during mechanical ventilation is feasible. They have also reported that the inhaled drugs administered during mechanical ventilation provide greater and faster clinical outcomes than when delivering during spontaneous unassisted breathing. Researchers studied factors that would affect aerosol delivery during mechanical ventilation. Even with the tremendous amount of publications in this area, there have still been no recommendations or guidelines released to help respiratory therapists in their decision as to when to deliver aerosol to ventilated patients. Mostly, respiratory therapists read the literature and decide accordingly what to do and which device to use for their patients. This puts the patients at risk of receiving a sub-therapeutic or toxic dose of the inhaled aerosol. Some studies raise an alarm of physician decision upon reading any released publication related to aerosol delivery in mechanical ventilation without a good trusted recommendation and guidelines. This increases the need for the development of recommendations and guidelines, by a trusted board or society, for aerosol delivery to such critically ill patients. To summarize, inhaled drugs administered to critically ill patients is of benefit compared to taking the patient off the ventilator and delivering during spontaneous unassisted breathing. However, dependable guidelines are needed to optimize aerosol delivery.

Clinical outcome associated with the use of different inhalation method with and without humidification in asthmatic mechanically ventilated patients

Article

Apr 2017

Background: Inhaled-medication delivered during mechanical-ventilation is affected by type of aerosol-generator and humidity-condition. Despite many in-vitro studies related to aerosol-delivery to mechanically-ventilated patients, little has been reported on clinical effects of these variables. The aim of this study was to determine effect of humidification and type of aerosol-generator on clinical status of mechanically ventilated asthmatics. Method: 72 (36 females) asthmatic subjects receiving invasive mechanical ventilation were enrolled and assigned randomly to 6 treatment groups of 12 (6 females) subjects each received, as possible, all inhaled medication using their assigned aerosol generator and humidity condition during delivery. Aerosol-generators were placed immediately after humidifier within inspiratory limb of mechanical ventilation circuit. First group used vibrating-mesh-nebulizer (Aerogen Solo; VMN) with humidification; Second used VMN without humidification; Third used metered-dose-inhaler with AeroChamber Vent (MDI-AV) with humidification; Forth used MDI-AV without humidification; Fifth used Oxycare jet-nebulizer (JN) with humidification; Sixth used JN without humidification. Measured parameters included clinical-parameters reflected patient response (CP) and endpoint parameters e.g. length-of-stay in the intensive-care-unit (ICU-days) and mechanical-ventilation days (MV-days). Results: There was no significant difference between studied subjects in the 6 groups in baseline of CP. VMN resulted in trend to shorter ICU-days (∼1.42days) compared to MDI-AV (p = 0.39) and relatively but not significantly shorter ICU-days (∼0.75days) compared JN. Aerosol-delivery with or without humidification did not have any significant effect on any of parameters studied with very light insignificant tendency of delivery at humid condition to decrease MV-days and ICU-days. No significant effect was found of changing humidity during aerosol-delivery to ventilated-patient. Conclusions: VMN to deliver aerosol in ventilated patient resulted in trend to decreased ICU-days compared to JN and MDI-AV. Aerosol-delivery with or without humidification did not have any significant effect on any of parameters studied. However, we recommend increasing the number of patients studied to corroborate this finding.

Nebulized Antibiotics for Ventilator-associated Pneumonia: Next Steps After the Meta-analyses

Article

May 2016
Clin Pulm Med

Ventilator-associated pneumonia (VAP) represents a major clinical challenge for all physicians caring for critically ill patients. Important concerns regarding the optimum treatment regimen for the management of pulmonary infections-such as the choice of antibiotic, the dosing, the duration of therapy, and drug delivery to the infected tissue-play an even more prominent role in the management of VAP. Patients with VAP are usually severely ill and have already been exposed to prolonged periods of intensive care; therefore, the safety margin for error is narrowed. Nebulized antibiotics represent a promising way to deliver high doses to the lung tissue with fewer concerns regarding systemic toxicity. In the context of multidrug-resistant VAP, where therapeutic options may be reduced to more toxic drugs, nebulized antibiotics may be a reasonable and logical choice. While most studies focused on the adjunctive role (ie, complementary to intravenous infusion) of nebulized antibiotics, some reports have suggested that nebulization may be effective even as a single therapy. Nevertheless, important differences in nebulization techniques contribute to the difficulty in obtaining robust data regarding the efficacy of nebulized therapy. Two recent meta-analyses have evaluated the role of nebulized antibiotics for VAP, one of them focusing specifically on nebulized polymyxin and the other assessing the role of nebulization therapy regardless of the drug used. Although conceptually different, both studies concluded that nebulized therapy could indeed play a significant role in the management of VAP. In this review, we reassess the evidence for nebulized antibiotics and provide guidance for future studies in this field to fill the knowledge gaps.

Device Selection and Outcomes of Aerosol Therapy: Evidence-Based Guidelines

Article

Full-text available

Inhaled Bronchodilator Administration During Mechanical Ventilation: How to Optimize It, and For Which Clinical Benefit?

Article

Full-text available

Mar 2008

Bronchodilators are frequently used in ICU patients, and are the most common medications administered by inhalation during mechanical ventilation. The amount of bronchodilator that deposits at its site of action depends on the amount of drug, inhaled mass, deposited mass, and particle size distribution. Mechanical ventilation challenges both inhaled mass and lung deposition by specific features, such as a ventilatory circuit, an endotracheal tube, and ventilator settings. Comprehensive in vitro studies have shown that an endotracheal tube is not as significant a barrier for the drug to travel as anticipated. Key variables of drug deposition are attachments of the inhalation device in the inspiratory line 10 to 30 cm to the endotracheal tube, use of chamber with metered-dose inhaler, dry air, high tidal volume, low respiratory frequency, and low inspiratory flow, which can increase the drug deposition. In vivo studies showed that a reduction by roughly 15% of the respiratory resistance was achieved with inhaled bronchodilators during invasive mechanical ventilation. The role of ventilatory settings is not as clear in vivo, and primary factors for optimal delivery and physiologic effects were medication dose and device location. Nebulizers and pressurized metered-dose inhalers can equally achieve physiologic end points. The effects of bronchodilators should be carefully evaluated, which can easily be done with the interrupter technique. With the non-invasive ventilation, the data regarding drug delivery and physiologic effects are still limited. With the bilevel ventilators the inhalation device should be located between the leak port and face mask. Further studies should investigate the effects of inhaled bronchodilators on patient outcome and methods to optimize delivery of inhaled bronchodilators during non-invasive ventilation.

Aerosol Delivery During Mechanical Ventilation: From Basic Techniques to New Devices

Article

Full-text available

Mar 2008

Rajiv Dhand

Pressurized metered-dose inhalers (pMDIs) and nebulizers are routinely employed for aerosol delivery in mechanically ventilated patients. A significant proportion of the aerosol deposits in the ventilator circuit and artificial airway, thereby reducing the inhaled drug mass. Factors influencing aerosol delivery during mechanical ventilation differ from those in spontaneously breathing patients. The English language literature on aerosol delivery during mechanical ventilation was reviewed. Marked variations in the efficiency of drug delivery with pMDIs and nebulizers occur due to differences in the technique of administration. Careful attention to five factors, viz., the aerosol generator, aerosol particle size, conditions in the ventilator circuit, artificial airway, and ventilator parameters, is necessary to optimize aerosol delivery during mechanical ventilation. Factors influencing drug delivery during NPPV are not well understood, and the efficiency of aerosol delivery in this setting is lower than that during invasive mechanical ventilaiton. With an optimal technique of administration the efficiency of aerosol delivery during mechanical ventilation is similar to that achieved during spontaneous breathing. Further research is needed to optimize aerosol delivery during NPPV.

Influence of Nebulizer Type, Position, and Bias Flow on Aerosol Drug Delivery in Simulated Pediatric and Adult Lung Models During Mechanical Ventilation

Article

Full-text available

Jul 2010

The effectiveness of aerosol drug delivery during mechanical ventilation is influenced by the patient, ventilator, and nebulizer variables. The impact of nebulizer type, position on the ventilator circuit, and bias flow on aerosol drug delivery has not been established for different age populations. To determine the influence of nebulizer position and bias flow with a jet nebulizer and a vibrating-mesh nebulizer on aerosol drug delivery in simulated and mechanically ventilated pediatric and adult patients. Albuterol sulfate (2.5 mg) was nebulized with a jet nebulizer and a vibrating-mesh nebulizer, using simulated pediatric and adult lung models. The 2 nebulizer positions were: (1) jet nebulizer placed 15 cm from the Y-piece adapter, and vibrating-mesh nebulizer attached directly to the Y-piece; and (2) jet nebulizer placed prior to the heated humidifier with 15 cm of large-bore tubing, and vibrating-mesh nebulizer positioned at an inlet to the humidifier. A ventilator with a heated humidifier and ventilator circuit was utilized in both lung models. The adult ventilator settings were V(T) 500 mL, PEEP 5 cm H2O, respiratory rate 20 breaths/min, peak inspiratory flow 60 L/min, and descending ramp flow waveform. The pediatric ventilator settings were V(T) 100 mL, PEEP 5 cm H2O, respiratory rate 20 breaths/min, inspiratory time 1 s. We tested bias flows of 2 and 5 L/min. The adult and pediatric lung models used 8-mm and 5-mm inner-diameter endotracheal tubes, respectively. Each experiment was run 3 times (n = 3). The albuterol sulfate was eluted from the filter and analyzed via spectrophotometry (276 nm). Nebulizer placement prior to the humidifier increased drug delivery with both the jet nebulizer and the vibrating-mesh nebulizer, with a greater increase with the vibrating-mesh nebulizer. Higher bias flow reduced drug delivery. Drug delivery with the vibrating-mesh nebulizer was 2-4-fold greater than with the jet nebulizer at all positions (P < .05) in both lung models. During simulated mechanical ventilation in pediatric and adult models, bias flow and nebulizer type and position impact aerosol drug delivery.

Evaluation of Aerosol Generator Devices at 3 Locations in Humidified and Non-humidified Circuits During Adult Mechanical Ventilation

Article

Full-text available

Jul 2010

The position of the jet or ultrasonic nebulizer in the ventilator circuit impacts drug delivery during mechanical ventilation, but has not been extensively explored, and no study has examined all of the commonly used nebulizers. Drug delivery from jet, vibrating-mesh, and ultrasonic nebulizers and pressurized metered-dose inhaler (pMDI) with spacer was compared in a model of adult mechanical ventilation, with heated/humidified and non-humidified ventilator circuits. Albuterol sulfate was aerosolized at 3 circuit positions: (1) between the endotracheal tube and the Y-piece; (2) 15 cm from Y-piece; and (3) 15 cm from the ventilator, with each device (n = 3) using adult settings (tidal volume 500 mL, ramp flow pattern, 15 breaths/min, peak inspiratory flow 60 L/min, and PEEP 5 cm H(2)O). The drug deposited on an absolute filter distal to an 8.0-mm inner-diameter endotracheal tube was eluted and analyzed via spectrophotometry (276 nm), and is reported as mean +/- SD percent of total nominal or emitted dose. The vibrating-mesh nebulizer, ultrasonic nebulizer, and pMDI with spacer were most efficient in position 2 with both non-humidified (30.2 +/- 1.0%, 24.7 +/- 4.4%, and 27.8 +/- 3.3%, respectively) and heated/humidified circuits (16.8 +/- 2.6%, 16.5 +/- 4.3%, and 17 +/- 1.0%, respectively). In contrast, the jet nebulizer was most efficient in position 3 under both non-humidified (14.7 +/- 1.5%) and heated/humidified (6.0 +/- 0.1%) conditions. In positions 2 and 3, all devices delivered approximately 2-fold more drug under non-humidified than under heated/humidified conditions (P < .01). At position 1 only the pMDI delivered substantially more drug than with the non-humidified circuit. During mechanical ventilation the optimal drug delivery efficiency depends on the aerosol generator, the ventilator circuit, and the aerosol generator position.

Aerosol delivery by an ultrasonic nebulizer during different mechanical ventilation settings in a lung model - A pilot study

Article

Full-text available

Feb 2009

Aerosol delivery of Iloprost is a promising therapeutic approach. The aim of this study was to determine the output of an ultrasonic nebulizer in different ventilation set-ups at the tip of different endotracheal tubes. In set-up A, an ultrasonic nebulizer was connected directly to the endotracheal tube. In set-up B, the nebulizer was incorporated into the inspiratory limb of the ventilator circuit; a bypass arrangement allowed to selectively direct the expiratory air discharged from the model lung. The test lungs were ventilated through a standard endotracheal tube (ET) and through a double-lumen tube (DLT). The nebulizer was filled with 5 ml of a Tc-99m 0.9%-NaCl solution. After nebulization, distribution of radioactivity was detected by gamma scintigraphy. Set-up A, ventilation in volume-controlled mode (VCV) via an ET: Delivered dose (1.61 +/- 0.41 ml), nebulization time 10.13 +/- 1.71 min. Set-up A, pressure-controlled ventilation (PCV), via a DLT: Delivered dose (1.33 +/- 0.88 ml), nebulization time 13.27 +/- 2.58 min. Set-up B, VCV mode via an ET: Delivered dose (1.57 +/- 0.44 ml), nebulization time (25.9 +/- 3.8 min). Set-up B, PCV mode, via a DLT: Delivered dose (1.3 +/- 0.17 ml), nebulization time (25.6 +/- 4.0 min). Set-up B did not yield a significantly higher output (p < 0.05), but the nebulization time was significantly longer (p > 0.05) compared with set-up A. Set-ups which involve connecting the nebulizer directly to an ET or a DLT exhibit sufficient output of aerosol and short nebulization times.

A Comparison of Commercial Jet Nebulizers

Article

Full-text available

Dec 1994

Seventeen commercially available jet nebulizers from 15 commercial sources were studied (Acorn-I, Acorn-II, AquaTower, AVA-NEB, Cirrhus, Dart, DeVilbiss 646, Downdraft, Fan Jet, MB-5, Misty Neb, PARI LC JET, PARI-JET, Salter 8900, Sidestream, Updraft-II, Whisper Jet). All nebulizers were filled with 2 ml of saline solution plus 0.5 ml of albuterol and powered with the same source (DeVilbiss PulmoAide). We compared total output (TO), time for total output (TTO), and percent output in respirable range (PORR). The TO was obtained by weighing before nebulization and at the point of eight-fold decline in output. The TTO was calculated from initiation of nebulization to the point of eightfold decline in output. The PORR was measured by a laser particle analyzer in continuous nebulization to the same point of abrupt drop in output. The TO varied from 0.98 To 1.86 ml (p < 0.0001) with the Acorn-I, Acorn-II, Updraft-II, and Sidestream, significantly greater than the others (p < 0.05). The TTO varied from 2.28 to 20.95 min (p < 0.0001). The AquaTower, PARI LC JET and PARI-JET, DeVilbiss, and Dart were significantly shorter than the others (p < 0.05). The PORR varied from 21.89 to 71.95 percent (p < 0.0001). The Sidestream was significantly greater than all others (p < 0.05). The PARI LC JET and PARI-JET were, in turn, significantly greater than the remaining models (p < 0.05). To combine these characteristics, we calculated respirable particle delivery rate (RPDR) by dividing TO by TTO and multiplying by PORR. The RPDR varied from 0.03 ml/min to 0.26 ml/min (p < 0.0001). The PARI LC JET (0.24 ml/min) and the PARI-JET (0.26 mg/min) had a RPDR that was significantly greater than the other models except the AquaTower, which, however, had a markedly variable performance. The Sidestream (0.19 mg/ml) did not differ significantly from the above group, nor from the DeVilbiss and Downdraft. All other models had significantly lower outputs (p < 0.05). We conclude that the output characteristics of commercial nebulizers vary greatly and will impact on the time required for treatment as well as the total amount of drug delivered to the lungs.

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia

Article

Full-text available

May 1996

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

The science of nebulised drug delivery

Article

Full-text available

May 1997

Efficacy of Metered-Dose Inhaler Administration of Albuterol in Intubated Infants

Article

Full-text available

Aug 1997

To compare the safety and efficacy of metered-dose inhaler (MDI) albuterol to nebulized (NEB) albuterol administration. A randomized, triple-blinded, crossover study. A pediatric ICU in a tertiary care children's hospital. Eleven intubated infants with bronchiolitis. Subjects received four puffs of MDI albuterol (360 microg) and 3 mL of NEB saline solution placebo or 0.3 mL of NEB albuterol (1.5 mg) and MDI saline solution placebo. Each set of albuterol and saline solution placebo was administered after direct attachment of delivery device to the endotracheal tube and bag-valve system. Subjects received the opposite sequence 4 h after the initial sequence. The second sequence was given first the next day, and the first sequence was administered 4 h later. Respiratory system compliance and resistance were measured at baseline and 30 min, 1 h, 2 h, and 4 h after each set of placebo and albuterol. There was an appreciable improvement in compliance and resistance for up to 2 h following both methods of administration. However, the degree of improvement was not significantly different (p>0.05) between the two methods. Neither method caused a significant change in resistance when measured at 4 h after albuterol/placebo administration. No evidence of toxicity was detected. MDI-administered albuterol is as safe and efficacious as nebulized-administered albuterol in intubated infants with bronchiolitis. Generalizability of these results is limited by differences in drug delivery with different brands of nebulizers and spacers and sites of attachment.

American College of Chest Physicians; American College of Asthma, Allergy, and Immunology. Device selection and outcomes of aerosol therapy: Evidence-based guidelines. American College of Chest Physicians/American College of Asthma, Allergy, and Immunology

Article

Full-text available

Feb 2005

The proliferation of inhaler devices has resulted in a confusing number of choices for clinicians who are selecting a delivery device for aerosol therapy. There are advantages and disadvantages associated with each device category. Evidence-based guidelines for the selection of the appropriate aerosol delivery device in specific clinical settings are needed. (1) To compare the efficacy and adverse effects of treatment using nebulizers vs pressurized metered-dose inhalers (MDIs) with or without a spacer/holding chamber vs dry powder inhalers (DPIs) as delivery systems for beta-agonists, anticholinergic agents, and corticosteroids for several commonly encountered clinical settings and patient populations, and (2) to provide recommendations to clinicians to aid them in selecting a particular aerosol delivery device for their patients. A systematic review of pertinent randomized, controlled clinical trials (RCTs) was undertaken using MEDLINE, EmBase, and the Cochrane Library databases. A broad search strategy was chosen, combining terms related to aerosol devices or drugs with the diseases of interest in various patient groups and clinical settings. Only RCTs in which the same drug was administered with different devices were included. RCTs (394 trials) assessing inhaled corticosteroid, beta2-agonist, and anticholinergic agents delivered by an MDI, an MDI with a spacer/holding chamber, a nebulizer, or a DPI were identified for the years 1982 to 2001. A total of 254 outcomes were tabulated. Of the 131 studies that met the eligibility criteria, only 59 (primarily those that tested beta2-agonists) proved to have useable data. None of the pooled metaanalyses showed a significant difference between devices in any efficacy outcome in any patient group for each of the clinical settings that was investigated. The adverse effects that were reported were minimal and were related to the increased drug dose that was delivered. Each of the delivery devices provided similar outcomes in patients using the correct technique for inhalation. Devices used for the delivery of bronchodilators and steroids can be equally efficacious. When selecting an aerosol delivery device for patients with asthma and COPD, the following should be considered: device/drug availability; clinical setting; patient age and the ability to use the selected device correctly; device use with multiple medications; cost and reimbursement; drug administration time; convenience in both outpatient and inpatient settings; and physician and patient preference.

Aerosol Delivery During Mechanical Ventilation: From Basic Techniques to New Devices

Article

Full-text available

Feb 2008

Rajiv Dhand

Inhaled Bronchodilator Administration During Mechanical Ventilation: How to Optimize It, and For Which Clinical Benefit?

Article

Full-text available

Mar 2008

Physicochemical aspects of nebulisation: comparison of five models of jet nebulisers

Article

Jan 2000

Determinants of Aerosolized Albuterol Delivery to Mechanically Ventilated Infants

Article

Jun 1996

Denise M. Coleman

An in vitro lung model and a volume ventilator were used to evaluate the delivery of aerosolized albuterol through an infant ventilator circuit. We compared the following : continuous nebulization (CNA) and intermittent nebulization (INA) ; various nebulizer gas flows, 5.0, 6.5, and 8.0 L/min ; and duty cycle of 33% and 50%. The efficiency and consistency of aerosol delivery by metered-dose inhaler (MDI) with four different spacer devices and by nebulizer positioned at the manifold and at the same position as the MDI were also evaluated. A volume ventilator (Servo 900B) was used with settings selected to reflect those of a moderately to severely ill 4-kg infant. A 3.5-mm endotracheal tube was used in all experiments. A specific type of nebulizer used (Airlife Misty Neb ; Baxter ; Valencia, Calif) and several spacers were studied (Aerochamber and Aerovent, Diemolding Healthcare Div, Canastota, NY ; ACE, Monaghan Medical Corp, Plattsburgh, NY ; and an in-line MDI adapter, Instrumentation Industries Inc, Pittsburgh). CNA delivered significantly more aerosol to the lung model (4.8±0.6% of the starting dose) than INA (3.8±0.3% ; p<0.01). There was a significant stepwise decrease in aerosol delivery with increasing nebulizer flow (4.8±1.3% at 5.0 L/min ; 3.7±1.1% at 6.5 L/min ; and 2.7±1.1% at 8.0 L/min). Increasing duty cycle did not significantly affect delivery. Overall the spacers with MDI were more efficient than the nebulizer in either position delivering about twice the percentage of the starting dose than the nebulizers. All modes of delivery, except the Aerochamber, demonstrated a marked degree of variability. Most of the starting dose of albuterol either remained in the nebulizer (30.4±6.0% at 5.0 L/min and 25.3±4.1% at 8.0 L/min) or was deposited in the inspiratory tubing (34.7±0.7% at 5.0 L/min and 43.7±4.9% at 8.0 L/min) in our system. In conclusion, we have confirmed that aerosol delivery depends on the mode of delivery and the operating conditions. Although delivery with an MDI and spacer is more efficient than a nebulizer, both methods may produce high variability depending on the method or spacer used.

The Role of Dose Volume in Delivering Albuterol Sulfate With a Low Residual Volume Nebulize

Article

Oct 2003

James B Fink

Salbutamol delivery in an in vitro pediatric ventilator-lung model: Comparison of jet, ultrasonic and MESH nebulisers

Article

Dec 2010

OBJECTIVE:: To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. DESIGN:: In vitro, laboratory study. SETTING:: Research laboratory of a university hospital. INT ERVENTIONS:: Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. MEASUREMENTS AND MAIN RESULTS:: The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39-2.70 μm) reached the end of the endotracheal tube. CONCLUSIONS:: Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator-lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer. © 2013 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

In vitro comparison of a novel nebulizer with ultrasonic and pneumatic nebulizers

Article

Feb 2003
J ALLERGY CLIN IMMUN

Albuterol delivery in an in vitro pediatric ventilator lung model

Article

Jan 2013
PEDIATR CRIT CARE ME

OBJECTIVE:: To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. DESIGN:: In vitro, laboratory study. SETTING:: Research laboratory of a university hospital. INTERVENTIONS:: Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. MEASUREMENTS AND MAIN RESULTS:: The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39-2.70 µm) reached the end of the endotracheal tube. CONCLUSIONS:: Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator-lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

Aerosol Deposition in Health and Disease

Article

Jun 2012
J AEROSOL MED PULM D

Chantal Darquenne

The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. This article reviews the main mechanisms affecting the transport and deposition of inhaled aerosol in the human lung. Aerosol deposition in both the healthy and diseased lung is described mainly based on the results of human studies using nonimaging techniques. This is followed by a discussion of the effect of flow regime on aerosol deposition. Finally, the link between therapeutic effects of inhaled drugs and their deposition pattern is briefly addressed. Data show that total lung deposition is a poor predictor of clinical outcome, and that regional deposition needs to be assessed to predict therapeutic effectiveness. Indeed, spatial distribution of deposited particles and, as a consequence, drug efficiency is strongly affected by particle size. Large particles (>6 μm) tend to mainly deposit in the upper airway, limiting the amount of drugs that can be delivered to the lung. Small particles (<2 μm) deposit mainly in the alveolar region and are probably the most apt to act systemically, whereas the particle in the size range 2-6 μm are be best suited to treat the central and small airways.

Jet nebulisers for pulmonary delivery

Article

Mar 1996
INT J PHARMACEUT

Nebulisers are widely used clinically to produce aerosols for a range of applications. This paper reviews the many factors which determine the particle size of the aerosol and drug output and describes their potential usefulness for novel drug delivery.There are numerous commercially available nebulisers, and their design is an important factor governing aerosol size and fluid output. Recent designs have included developments to reduce the proportion of drug lost during exhalation with traditional continuous output nebùlisers.The rate of gas flow driving atomization is a major determinant of aerosol size; there being an inverse relationship between droplet size and flow rate, due to the increased shearing forces at higher flow rates. Although droplet size is largely independent of fill volume, the proportion of available drug increases with increased fill volumes, since some fluid is invariably retained within the nebulisation chamber at the end of atomization. During use the temperature of the fluid within the nebuliser significantly decreases. This may result in precipitation of poorly soluble drugs and produce variability in droplet size due to changes in the physicochemical properties of nebuliser fluids. Mean aerosol size is inversely proportional to viscosity. However, although high viscosity fluids produce small droplets, they require longer to nebulise to dryness and are retained to a greater extent. Reducing the surface tension of fluids tends to produce aerosols of smaller size. Thus, the size and dose of aerosol available for inhalation by a patient is a complex function of all these factors, whilst the dose inhaled and deposited in the airways is highly dependent on patient-related factors.

Pentamidine isethionate delivery from jet nebulisers

Article

Sep 1992
INT J PHARMACEUT

This study has investigated the properties of aerosols of pentamidine isethionate produced by two jet nebulisers commonly used in clinical practice. The size characteristics of the emitted aerosols varied throughout the time that drug solutions were nebulised, particularly at low gas flow rates. The aqueous solubility of pentamidine isethionate was found to be highly temperature dependent. As the temperature of solutions within the nebulisers decreased by up to 13°C, recrystallization of drug occurred. Approx. 50% of drug available in the nebuliser was available for delivery from the nebulisers, the remainder being associated with the devices.

Omron NE U22: Comparison Between Vibrating Mesh and Jet Nebulizer

Article

Jun 2010
J AEROSOL MED PULM D

To overcome the limitations of conventional jet nebulizers, vibrating mesh technology has been commercialized. The present article is designed to address clinically relevant issues for routine aerosol therapy for a vibrating mesh nebulizer, the Omron NE U22, compared to traditional jet nebulizers. Inhaled mass (IM), residual activity, particle distribution, including mass median aerodynamic diameter (MMAD) and run time, were determined for radiolabeled albuterol (2.5 mg/3 mL). Omron NE U22, Pari LC Plus, and Sidestream nebulizers were tested. The Omron was tested in two positions, tilted and horizontal. Finally robustness of the Omron NE U22 was determined by repeating treatment 60 times. All Omron experiments were performed using continuous operation. IM for Omron and Pari were similar (20% of nebulizer charge) and greater than the Sidestream (10%). MMADs were similar for all devices but variability was much greater for Omron in the horizontal position. Run time in the tilted position was three times longer when compared to the horizontal (p = 0.02). IM and MMAD were unchanged after Omron robustness testing. Position was an important factor for the mesh device affecting run time and variability in particle distribution. Using a common commercial formulation and continuous operation, drug delivery was similar to an efficient jet nebulizer. The Omron mesh tolerated repeated use with the albuterol formulation.

Consensus Summary of Aerosolized Antimicrobial Agents: Application of Guideline Criteria

Article

Jun 2010
PHARMACOTHERAPY

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Optimisation de la nébulisation du salbutamol chez l'enfant sous ventilation mécanique /

Article

Ermindo R. Di Paolo

Thèse pharm. Lausanne (pas d'échange). Bibliogr.

Paradoxical Bronchospasm After Use of Inhalation Aerosols: A Review of the Literature

Article

Feb 1991

Various formulations of beta-agonists and other bronchodilators have been associated with unexpected bronchoconstriction in certain individuals. Even though the number of affected individuals represents a relatively small percentage and the etiologies may differ among patients, it is important for the public to be aware of the potential for paradoxical bronchospasm and for the physician to investigate each case accordingly.

Droplets produced by medical nebulizers. Some factors affecting their size and solute concentration

Article

Jul 1990

The effect of nebulizer solution temperature and dilution air humidity on the size and solute concentration of aqueous aerosol droplets were studied. Four combinations of jet-nebulizers with air compressors or oxygen sources and one ultrasonic nebulizer were tested. The temperature to which the nebulizer solution of each system fell during generation was measured. The nebulizers were then kept at set temperatures, generated aerosols collected and either droplet size or solute concentration measured. The droplet solute concentration was found to increase. The droplet size decreased along with the droplet solute concentration increase. The ultrasonic nebulizer also was tested: its high output made the concentration of the solution in the droplets much more stable. However, the proportion of droplets depositing in the tubing and valves changed markedly with aerosol flow rate. The potential for large changes in droplet solute concentration, droplet size and output during nebulization should be considered in therapeutic and diagnostic applications of nebulized aerosols.

Some Factors Associated with the Ultrasonic Nebulization of Proteins

Article

Feb 1995

Ultrasonic nebulization of lactate dehydrogenase (LDH) was investigated using a DeVilbiss "Aerosonic" nebulizer. The enzyme (8ml, 0.025 mg/ml Na2HPO4, pH 7.0) was completely inactivated after 20 minutes of operation. However, the inactivation profile observed during ultrasonic nebulization was different from that previously observed using air-jet nebulization. At least two mechanisms are involved, one associated with heating and the other with aerosol production. By preventing heating of the nebulizer fluid during operation, the denaturation profile was dramatically altered. By additionally including 0.01% w/v Tween 80 or 1% w/v PEG 8000, almost all activity was retained. Similar results were obtained by preventing aerosol production and heating. However, 100% of activity was lost when heating was allowed to occur without aerosol formation. The results demonstrate that cooling in conjunction with a surfactant is one approach that could be used to stabilize proteins to ultrasonic nebulization. However, cooling also significantly reduced solute output from the nebulizer. When operated at 10 degrees C output was negligible. At 50 degrees C the output was 5x greater than that found at room temperature. The median droplet size (micron(s)) was not significantly influenced by the operating temperature of the nebulizer fluid (3.6 +/- 0.4, 21 degrees C; 3.9 +/- 0.2, 50 degrees C, p = NS (n = 6)) although the size distribution was noted to increase at the higher temperature.

Delivery of Ultrasonic Nebulized Aerosols to a Lung Model during Mechanical Ventilation

Article

Nov 1993
Am J Respir Crit Care Med

Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted.

Determinants of aerosolized albuterol delivery to mechanically ventilated infants

Article

Jun 1996

An in-vitro lung model and a volume ventilator were used to evaluate the delivery of aerosolized albuterol through an infant ventilator circuit. We compared the following: continuous nebulization (CNA) and intermittent nebulization (INA); various nebulizer gas flows, 5.0, 6.5,and 8.0 L/min; and duty cycle of 33% and 50%. The efficiency and consistency of aerosol delivery by metered-dose inhaler (MDI) with four different spacer devices and by nebulizer positioned at the manifold and at the same position as the MDI were also evaluated. A volume ventilator (Servo 900B) was used with settings selected to reflect those of a moderately to severely ill 4-kg infant. A 3.5-mm endotracheal tube was used in all experiments. A specific type of nebulizer used (Airlife Misty Neb; Baxter; Valencia, Calif) and several spacers were studied (Aerochamber and Aerovent, Monaghan Medical Corporation in Plattsburgh, NY [corrected]; ACE, Diemolding Healthcare Division in Canastota, NY [corrected]; and an in-line MDI adapter, Instrumentation Industries Inc, Pittsburgh). CNA delivered significantly more aerosol to the lung model (4.8 +/- 0.6% of the starting dose) than INA (3.8 +/- 0.3%; p<0.01). There was a significant stepwise decrease in aerosol delivery with increasing nebulizer flow (4.8 +/- 1.3% at 5.0 L/min; 3.7 +/- 1.1% at 6.5 L/min; and 2.7 +/- 1.1% at 8.0 L/min). Increasing duty cycle did not significantly affeet delivery. Overall the spacers with MDI were more efficient than the nebulizer in either position delivering about twice the percentage of the starting dose than the nebulizers. All modes of delivery, except the Aerochamber, demonstrated a marked degree of variability. Most of the starting dose of albuterol either remained in the nebulizer (30.4 +/- 6.0% at 5.0 L/min and 25.3 +/- 4.1% at 8.0 L/min) or was deposited in the inspiratory tubing (34.7 +/- 0.7% at 5.0 L/min and 43.7+/- 4.9% at 8.0 L/min) in our system. In conclusion, we have confirmed that aerosol delivery depends on the mode of delivery and the operating conditions. Although delivery with an MDI and spacer is more efficient than a nebulizer, both methods may produce high variability depending on the method or spacer used.

Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation

Article

May 1997

Increased delivery of aerosol to a model lung (attached to a mechanical ventilator) has been demonstrated with an ultrasonic nebulizer as compared to a jet nebulizer. This study examined whether the increased aerosol deposition with an ultrasonic nebulizer could also be demonstrated in vivo. Seven patients (6 male and 1 female) were studied during mechanical ventilalion (Siemens Servo 900C, Middlesex, UK) after open heart surgery. Two studies were performed in each patient. In the first study, aerosol was delivered via a Siemens Servo 945 nebulizer system (high setting) driving a System 22 Acorn jet nebulizer (Medic-Aid, Sussex, UK) containing 3 mL (99m)technetium-labelled human serum albumin (99mTc-HSA) (50 microg; activity 74 MBq). In the second study, a DP100 ultrasonic nebulizer (DP Medical, Meylan, France) containing 12 mL 99mTc-HSA (50 microg; activity 185 MBq) was used. Pulmonary deposition was quantified using a gamma camera. The humidification of the circuit and the ventilator settings were kept constant according to the patient's clinical requirements. The total lung aerosol deposition (mean+/-SD), as a percentage of initial nebulizer activity, was greater using the ultrasonic nebulizer than using the jet nebulizer (53+/-1.4 vs 2.3+/-0.9%; p<0.002). The ultrasonic nebulizer was also associated with a reduction in the time required to complete nebulization (9 vs 21 min, respectively) (p<0.0001). Use of the DP100 ultrasonic nebulizer more than doubled lung deposition compared with the System 22 jet nebulizers in mechanically-ventilated patients. Their efficiency, speed of drug delivery, and compatibility with mechanical ventilator circuits make ultrasonic nebulizers potentially attractive for use during mechanical ventilation.

Nebuliser therapy in the intensive care unit

Article

May 1997

Evaporation of Aqueous Aerosols Produced by Jet Nebulizers: Effects on Particle Size and Concentration of Solution in the Droplets

Article

Feb 1994

Aqueous droplets produced by jet nebulizers can lose water by evaporation prior to entry into the patient's mouth, or a sizing device. Evaporation causes increase in the concentration of the solution in the droplet and reduction in size. These changes can complicate interpretation of results from experiments such as in vitro particle sizing or human respiratory tract deposition. We present experimental data obtained by nebulization of isotonic saline using a variety of aerosol delivery systems employing jet nebulizers. The impact of the evaporation phenomena is particularly great when a large volume of dry dilution air is mixed with the aerosol stream--a situation that is quite common in aerosol experiments. The experimental results approach the values calculated from the theoretical mass balance models in the limit of equilibrium between the droplets and the surrounding atmosphere.

Validation of Laser Diffraction Method as a Substitute for Cascade Impaction in the European Project for a Nebulizer Standard

Article

Feb 2001

The project for a European standard testing procedure to characterize nebulizers in terms of particle size distribution has been based on using the Andersen-Marple personal cascade impactor model 298 (A-MPCI) with a sodium fluoride reference solution. In the present study methods based on laser diffraction (Mastersizer-X) and time-of-flight (TOF)(APS) and another cascade impactor (GS1-CI) were compared with the A-MPCI. Two types of nebulizer (Pari LC+ and Microneb) were tested with all apparatuses, and a third type of nebulizer (NL9) was tested with the A-MPCI and Mastersizer-X. Nebulizers were charged with a solution of sodium fluoride in conditions reproducing the European Committee for Normalization (CEN) protocol. There was no difference between the Mastersizer-X and the A-MPCI or between the GS1-CI and the A-MPCI in terms of mass median aerodynamic diameter (MMAD). Comparison between the APS and the A-MPCI showed a significant difference with the Microneb. The geometric standard deviations (GSD) obtained with the A-MPCI were on average 10% greater than GSD obtained with the other apparatuses, but the differences were not statistically significant. We conclude that laser diffraction can be used for particle size distribution in the context of the European standard, and that the Mastersizer-X is particularly interesting for industrial practice in view of its simplicity and robustness.

An assessment of jet and ultrasonic nebulisers for the delivery of lactate dehydrogenase solutions

Article

Oct 2001
INT J PHARMACEUT

The aim of this study was to investigate the suitability of commercial jet and ultrasonic nebulisers for effective delivery of the model hydrophilic protein lactate dehydrogenase (LDH). Two jet nebulisers (Pari LC Plus and Pari LC Star) and two ultrasonic nebulisers (Sonix 2000 and Omron U1) were used to nebulise LDH solutions and the effects on protein activity and protein concentration determined. The size distribution of the aerosols produced, measured by laser diffraction analysis, temperature changes during nebulisation, the time to atomise a 5 ml dose volume and the mass output of the four nebulisers were compared. A twin impinger (TI) was used to collect the nebulised protein, which was assayed for total and active protein content. There was a large variation in the median size and size distribution of the aerosols produced by each of the nebulisers from LDH and Sørensen's modified phosphate buffer, and in the time taken to reach the sputtering phase of aerosolisation. During use, the concentration of LDH increased in the Omron U1 nebuliser, but did not change significantly in the others. The temperature of the protein solution decreased by approximately 8 degrees C during jet nebulisation but increased by 3 and 10 degrees C in the Omron U1 and Sonix 2000 nebulisers, respectively. Denaturation of LDH within the nebuliser reservoir, occurred in the order Sonix>Pari LC Plus>Pari LC Star>Omron U1, whilst the deposition of active and total protein within the stages and throat of the TI was a function of the particle size of the aerosols generated and the specific device used.

Nebulizers that Use a Vibrating Mesh or Plate with Multiple Apertures to Generate Aerosol

Article

Jan 2003

Rajiv Dhand

Several electronic nebulizer devices that use a vibrating mesh or plate with multiple apertures to generate a fine-particle, low-velocity aerosol have been marketed or will shortly become available for clinical use. These devices have a high efficiency of delivering aerosol to the lung, such that the nominal dose of drugs to be administered could be substantially reduced. Moreover, the volume of drug solution left in these new devices when the nebulization has ceased is negligible, so there is potential to improve the cost-effectiveness of administering expensive medications. Because these devices nebulize at a faster rate than conventional jet or ultrasonic nebulizers, the duration of each treatment could be shortened. These devices efficiently nebulize solutions and suspensions; they have been successfully used for aerosolizing insulin, other proteins and peptides, and fragments of DNA. They could be employed for a wide variety of clinical applications, including the delivery of aerosols for systemic therapy and gene transfer. These devices have overcome many of the limitations associated with conventional jet and ultrasonic nebulizers, and they offer the versatility to modify the aerosol characteristics according to the clinical application for which they are employed. With these devices clinicians will be able to precisely control drug delivery to the respiratory tract.

Factors affecting aerosol performance during nebulization with jet and ultrasonic nebulizers

Article

Sep 2003
EUR J PHARM SCI

Nebulization of aqueous solutions is a convenient delivery system to deliver drugs to the lungs because it can produce droplets small enough to reach the alveolar region. However, the droplet size might be affected by the changes in the temperature and the concentration of the nebulizing solution in the reservoir during nebulization. In this study, the changes in the droplet size over the nebulization time using a PariBoy air-jet and a Multisonic ultrasonic nebulizer have been studied. The findings were related to changes in the temperature, concentration, surface tension, viscosity and saturated vapour pressure of the nebulizing solution. By using the jet nebulizer, an increase in the droplet size followed by a decrease has been observed. This observation could be attributed to the approx. 7 degrees C reduction of the temperature during the first 2 min in the jet nebulizer reservoir which increased the viscosity of the nebulizing solution. After this initial period of time, the increasing drug concentration induced a reduction of the surface tension and, consequently, a decrease in the droplet size. However, with the ultrasonic nebulizer a temperature increase of approx. 20 degrees C during the first 6 min in the nebulizing solution was observed leading to a decrease in droplet size, viscosity and surface tension and an increasing saturated vapour pressure. This again led to smaller average droplet sizes.

Lung Deposition and Respirable Mass During Wet Nebulization

Article

Feb 2003

For metered dose inhalers (MDIs), high-flow cascade impaction with a United States Pharmacopia (USP) throat provides a useful prediction of in vivo lung and oropharyngeal aerosol deposition. Particles expected to deposit in the lung are included in the "fine particle fraction" measured on the bench. Comparable in vitro standards are not available for nebulizers. The present study compared aerosol deposition in an in vitro model using low-flow cascade impaction with deposition in vivo in human subjects. A low-flow (1 Lmin), 10-stage cascade impactor measured aerodynamic distributions of aerosolized interferon-gamma (IFN-gamma) from two nebulizers (Misty-Neb and AeroEclipse). (99m)Technetium diethylene triaminepenta-acetic acid ((99m)Tc-DTPA) was used as the radiolabel. Two bench conditions were specified: no breathing (standing cloud) and simulated ventilation with a piston pump (tidal volume 750 mL frequency 25 per minute and duty cycle 0.5). Mass median aerodynamic diameter (MMAD) for both nebulizers was affected by ventilation (Misty-Neb vs. AeroEclipse: 5.2 vs. 4.6 microm for standing cloud and 3.1 vs. 2.2 microm during ventilation). In three subjects, measured values of oropharyngeal deposition averaged 68.1 +/- 0.08% for Misty-Neb and 30.9 +/- 0.03% for AeroEclipse. In vivo deposition patterns compared to aerosol distributions from both nebulizers indicated that, for wet nebulization, penetration of aerosol beyond the upper airways (fine particle fraction) will occur only for aerosol particles below 2.5 microm. This assessment requires that the bench aerosol distribution be measured under conditions of clinical use (i.e., during tidal breathing).

In vitro evaluation of bronchodilator drug delivery by jet nebulization during pediatric mechanical ventilation

Article

Jul 2005
PEDIATR CRIT CARE ME

To determine the influence of jet nebulizer brands and nebulization mode on albuterol delivery in a mechanically ventilated pediatric lung model. In vitro, laboratory study. Research laboratory of a university hospital. Using albuterol as a marker, six jet nebulizers (Microneb NA420, Sidestream, Acorn II, Cirrus, Upmist, Micro Mist) were tested in four nebulization modes in a bench model mimicking the ventilatory pattern of a 10-kg infant (Galileo ventilator, Hamilton Medical). The amounts of albuterol deposited on the inspiratory filters at the end of the endotracheal tube were determined, as well as the pressure, flow profiles, and particle size distribution of the jet nebulizers. Pooling the data of the six jet nebulizer brands (n = 30) indicated that intermittent nebulization during the expiratory phase was more efficient (6.5 +/- 2.5% of the initial dose, p < .001) than intermittent nebulization during the inspiratory phase (1.9 +/- 1.2%) and continuous nebulization with air from the ventilator (4.0 +/- 1.5%) or from an external source (4.2 +/- 1.4%). The particle size distribution at 6 L x min(-1) was between 2.81 and 3.30 microm. In our in vitro pediatric lung model, the quantity of inhaled drug was low. Jet nebulizer brands and nebulization modes significantly affected drug delivery, and in vitro models designed for adults cannot be extrapolated to infants.

The influence of fluid physicochemical properties on vibrating-mesh nebulization

Article

Jul 2007
INT J PHARMACEUT

In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. Increased viscosity or ion concentration resulted in a decrease in droplet volume median diameter (VMD) and an increase in fine particle fraction (FPF). Moreover, increased viscosity resulted in prolonged nebulization and reduced output rate, particularly for the Omron nebulizer. Both nebulizers were unsuitable for delivery of viscous fluids since nebulization was intermittent or completely ceased at >1.92cP. The presence of ions reduced variability particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.

New technology offers new opportunities: continuous bronchodilator therapy during mechanical ventilation

Jan 2007
Respir Ther
29-32

J B Fink

Fink JB. New technology offers new opportunities: continuous bronchodilator therapy during mechanical ventilation. Respir Ther 2007; 2(4):29-32.

Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation

Jan 1993
872-877

S H Thomas
O Doherty
M J Page
C J Treacher
D F Nunan

Thomas SH, O'Doherty MJ, Page CJ, Treacher DF, Nunan TO. Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation. Am Rev Respir Dis 1993;148(4):872-877.

Society of Infectious Diseases Pharmacists Aerosolized Antimicrobials Task Force. Consensus summary of aerosolized antimicrobial agents: application of guideline criteria: insights from the Society of Infectious Diseases Pharmacists

Jan 2010
PHARMACOTHERAPY
562-584

J Le
E D Ashley
M M Neuhauser
J Brown
C Gentry
M E Klepser

Le J, Ashley ED, Neuhauser MM, Brown J, Gentry C, Klepser ME, et al; Society of Infectious Diseases Pharmacists Aerosolized Antimicrobials Task Force. Consensus summary of aerosolized antimicrobial agents: application of guideline criteria: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2010; 30(6):562-584.

Physicochemical Aspects and Efficiency of Albuterol Nebulization: Comparison of Three Aerosol Types in an In Vitro Pediatric Model

Abstract

No full-text available

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