Nebulizers.

Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g., infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: (1) pneumatic jet nebulizers (JN); (2) ultrasonic nebulizers (USN); and (3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 mL of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 mL and may be used for either bland aerosol therapy or continuous drug administration.

The Effects of Inspiratory Flows, Inspiratory Pause, and Suction Catheter on Aerosol Drug Delivery with Vibrating Mesh Nebulizers During Mechanical Ventilation.

Background: Some experts recommend specific ventilator settings during nebulization for mechanically ventilated patients, such as inspiratory pause, high inspiratory to expiratory ratio, and so on. However, it is unclear whether those settings improve aerosol delivery. Thus, we aimed to evaluate the impact of ventilator settings on aerosol delivery during mechanical ventilation (MV). Methods: Salbutamol (5.0 mg/2.5 mL) was nebulized by a vibrating mesh nebulizer (VMN) in an adult MV model. VMN was placed at the inlet of humidifier and 15 cm away from the Y-piece of the inspiratory limb. Eight scenarios with different ventilator settings were compared with endotracheal tube (ETT) connecting 15 cm from the Y-piece, including tidal volumes of 6-8 mL/kg, respiratory rates of 12-20 breaths/min, inspiratory time of 1.0-2.5 seconds, inspiratory pause of 0-0.3 seconds, and bias flow of 3.5 L/min. In-line suction catheter was utilized in two scenarios. Delivered drug distal to the ETT was collected by a filter, and drug was assayed by an ultraviolet spectrophotometry (276 nm). Results: Compared to the use of inspiratory pause, the inhaled dose without inspiratory pause was either higher or similar across all ventilation settings. Inhaled dose was negatively correlated with inspiratory flow with VMN placed at 15 cm away from the Y-piece (rs = -0.68, p < 0.001) and at the inlet of humidifier (rs = -0.83, p < 0.001). The utilization of in-line suction catheter reduced inhaled dose, regardless of the ventilator settings and nebulizer placements. Conclusions: When VMN was placed at the inlet of humidifier, directly connecting the Y-piece to ETT without a suction catheter improved aerosol delivery. In this configuration, the inhaled dose increased as the inspiratory flow decreased, inspiratory pause had either no or a negative impact on aerosol delivery. The inhaled dose was greater with VMN placed at the inlet of humidifier than 15 cm away the Y-piece.

Effect of Interrupting Heated Humidification on Nebulized Drug Delivery Efficiency, Temperature, and Absolute Humidity During Mechanical Ventilation: A Multi-Lab In Vitro Study.

Introduction: During mechanical ventilation (MV), inspired gases require heat and humidification. However, such conditions may be associated with reduced aerosol delivery efficiency. The practice of turning off heated humidification before nebulization and the impact of nebulization on humidity in a dry ventilator circuit remain topics of debate. This study aimed to assess the effect of turning off heated humidification on inhaled dose and humidity with nebulizer use during adult MV. Methods: A bronchodilator (albuterol) and two antibiotics (Colistimethate sodium and Amikacin sulfate) were nebulized with a vibrating mesh nebulizer placed at the humidifier inlet and in the inspiratory limb at the Y-piece. Additionally, albuterol was nebulized using a jet nebulizer in both placements. Aerosol particle size distribution was determined through a cascade impactor. Absolute humidity (AH) and temperature of inspired gases were determined with anemometer/hygrometers before, during, and after nebulization, before, during, and up to 60 minutes after interrupting active humidification. Aerosol collected on a filter distal to the endotracheal tube and on impactor stages were eluted and assayed by spectrophotometry. Results: The inhaled dose was greater when both nebulizers were placed at the humidifier inlet than the inspiratory limb at the Y-piece. Irrespective of the nebulizer types and placements, the inhaled dose either decreased or showed no significant change after the humidifier was turned off. The aerosol particle size ranged from 1.1 to 2.7 µm. With interruption of active humidification, humidity of inspired gas quickly dropped below recommended levels, and nebulization in dry ventilator circuit produced an AH between 10 and 20 mgH2O/L, lower than the recommended minimum of 30 mgH2O/L. Conclusion: Interrupting active humidification during MV before nebulization did not improve aerosol delivery efficiency for bronchodilator or antibiotics, but did reduce humidity below recommended levels.

Individualized aerosol medicine: Integrating device into the patient.

Pulmonary drug delivery is complex due to several challenges including disease-, patient-, and clinicians-related factors. Although many inhaled medications are available in aerosol medicine, delivering aerosolized medications to patients requires effective disease management. There is a large gap in the knowledge of clinicians who select and provide instructions for the correct use of aerosol devices. Since improper device selection, incorrect inhaler technique, and poor patient adherence to prescribed medications may result in inadequate disease control, individualized aerosol medicine is essential for effective disease management and control. The components of individualized aerosol medicine include: (1) Selecting the right device, (2) Selecting the right interface, (3) Educating the patient effectively, and (4) Increasing patient adherence to therapy. This paper reviews each of these components and provides recommendations to integrate the device and interface into the patient for better clinical outcomes.

A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial).

SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients were randomly assigned to receive open-labelled bovine nebulized surfactant or control (ratio 3-surfactant: 2-control). This was an exploratory dose-response study starting with 1080 mg of surfactant delivered at 3 time points (0, 8 and 24 h). After completion of 10 patients, the dose was reduced to 540 mg, and the frequency of nebulization was increased to 5/6 time points (0, 12, 24, 36, 48, and an optional 72 h) on the advice of the Trial Steering Committee. The co-primary outcomes were improvement in oxygenation (change in PaO2/FiO2 ratio) and ventilation index at 48 h. 20 patients were recruited (12 surfactant and 8 controls). Demographic and clinical characteristics were similar between groups at presentation. Nebulized surfactant administration was feasible. There was no significant improvement in oxygenation at 48 h overall. There were also no differences in secondary outcomes or adverse events. Nebulized surfactant administration is feasible in mechanically ventilated patients with COVID-19 but did not improve measures of oxygenation or ventilation.

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Influence of Mechanical Ventilation Modes on the Efficacy of Nebulized Bronchodilators in the Treatment of Intubated Adult Patients with Obstructive Pulmonary Disease.

BACKGROUND: Little has been reported in terms of clinical outcomes to confirm the benefits of nebulized bronchodilators during mechanical ventilation (MV). Electrical Impedance Tomography (EIT) could be a valuable method to elucidate this gap. OBJECTIVE: The purpose of this study is to evaluate the impact of nebulized bronchodilators during invasive MV with EIT by comparing three ventilation modes on the overall and regional lung ventilation and aeration in critically ill patients with obstructive pulmonary disease. METHOD: A blind clinical trial in which eligible patients underwent nebulization with salbutamol sulfate (5 mg/1 mL) and ipratropium bromide (0.5 mg/2 mL) in the ventilation mode they were receiving. EIT evaluation was performed before and after the intervention. A joint and stratified analysis into ventilation mode groups was performed, with p < 0.05. RESULTS: Five of nineteen procedures occurred in controlled MV mode, seven in assisted mode and seven in spontaneous mode. In the intra-group analysis, the nebulization increased total ventilation in controlled (p = 0.04 and ⅆ = 2) and spontaneous (p = 0.01 and ⅆ = 1.5) MV modes. There was an increase in the dependent pulmonary region in assisted mode (p = 0.01 and ⅆ = 0.3) and in spontaneous mode (p = 0.02 and ⅆ = 1.6). There was no difference in the intergroup analysis. CONCLUSIONS: Nebulized bronchodilators reduce the aeration of non-dependent pulmonary regions and increase overall lung ventilation but there was no difference between the ventilation modes. As a limitation, it is important to note that the muscular effort in PSV and A/C PCV modes influences the impedance variation, and consequently the aeration and ventilation values. Thus, future studies are needed to evaluate this effort as well as the time on ventilator, time in UCI and other variables.

In vitro model for investigating aerosol dispersion in a simulated COVID-19 patient during high-flow nasal cannula treatment.

The use of high-flow nasal cannula in the treatment of COVID-19 infected patients has proven to be a valuable treatment option to improve oxygenation. Early in the pandemic, there were concerns for the degree of risk of disease transmission to health care workers utilizing these treatments that are considered aerosol generating procedures. This study developed an in vitro model to examine the release of simulated patient-derived bioaerosol with and without high-flow nasal cannula at gas flow rates of 30 and 50 L/min. Aerosol dispersion was evaluated at 30 and 90 cm distances. Reduction of transmission risk was assessed using a surgical facemask on the manikin. Results indicated that the use of a facemask facilitated a 94-95% reduction in exhaled aerosol concentration at 30 cm and 22-60% reduction for 90 cm distance across both gas flow rates. This bench study confirms that this in vitro model can be used as a tool to assess the risk of disease transmission during aerosol generating procedures in a simulated patient and to test factors to mitigate the risk.

Evaluation of aerosol drug delivery with concurrent low- and high-flow nasal oxygen.

Question addressed by study: Administration of aerosol to patients receiving high-flow nasal oxygen (HFNO) ranges from concurrent aerosol delivery by mouthpiece to aerosol via cannula alone. This study examines the conditions to provide optimal aerosol delivery with low- or high-flow nasal oxygen with concurrent mouthpiece or through nasal cannula alone, and the impact on fugitive aerosols. Materials and methods: A vibrating mesh nebuliser delivered salbutamol via mouthpiece, aerosol holding chamber and nasal cannula to an adult head model simulating relaxed breathing. The mean±sd inhaled dose (%) was assayed from a filter distal to the trachea. Optical particle sizers were used to measure fugitive aerosol concentrations during aerosol delivery. Results: Concurrent low-flow nasal oxygen (LFNO) and aerosol delivery with a mouthpiece and aerosol holding chamber increased the inhaled dose (%) available, 31.44±1.33% when supplemented with 2 L·min-1 of nasal oxygen. Concurrent HFNO above 30 L·min-1 resulted in a lower inhaled dose (%) compared to aerosol delivered through HFNO alone. The addition of concurrent LFNO or HFNO resulted in no increase in aerosol levels in the test room. Answer to question posed: Concurrent LFNO with a mouthpiece and aerosol holding chamber is an effective and safe means of aerosol delivery.

Aerosol-Generating Procedures and Virus Transmission.

During the early phase of the COVID-19 pandemic, many respiratory therapies were classified as aerosol-generating procedures. This categorization resulted in a broad range of clinical concerns and a shortage of essential medical resources for some patients. In the past 2 years, many studies have assessed the transmission risk posed by various respiratory care procedures. These studies are discussed in this narrative review, with recommendations for mitigating transmission risk based on the current evidence.

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

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.

The Impact of High-Flow Nasal Cannula Device, Nebulizer Type, and Placement on Trans-Nasal Aerosol Drug Delivery.

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has been increasingly used in recent years. However, the effects of different HFNC devices, nebulizer types, and placement on aerosol deposition remain largely unknown. METHODS: An adult manikin with anatomically correct upper airway was used with a collection filter placed between the manikin's trachea and a breathing simulator, composed of a dual-chamber model lung driven by a critical care ventilator. Three HFNC device configurations were compared, with vibrating mesh nebulizer and small-volume nebulizer placed at the humidifier (inlet for Optiflow and outlet for Airvo 2) and proximal to the nasal cannula at gas flows of 10, 20, 40 and 60 L/min, in quiet and distressed breathing patterns. Albuterol (2.5 mg) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: At all settings, except when a nebulizer was placed proximal to the nasal cannula with the Optiflow and when the HFNC flow was set at 60 L/min, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer (all P < .05). With the exception of distressed breathing at an HFNC flow of 10 L/min, the inhaled dose with the vibrating mesh nebulizer placed at the humidifier was greater than with the vibrating mesh nebulizer placed proximal to the nasal cannula (all P < .05), Optiflow provided a higher inhaled dose than did Airvo 2 with either AirSpiral or 900PT501 circuits with the vibrating mesh nebulizer placed at the humidifier (all P < .05). CONCLUSIONS: During transnasal aerosol delivery, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer when the nebulizer was placed at the humidifier. With the vibrating mesh nebulizer placed at the humidifier and an HFNC flow > 10 L/min, the inhaled dose was higher than with the vibrating mesh nebulizer placed proximal to the nasal cannula, and the inhaled dose was higher with Optiflow than with Airvo 2.

Aerosol Delivery via Continuous High-Frequency Oscillation During Mechanical Ventilation.

BACKGROUND: As the use of continuous high-frequency oscillation combined with nebulization during mechanical ventilation becomes more prevalent clinically, it is important to evaluate its aerosol delivery efficacy. METHODS: A bench study was conducted that simulated 2 adult and 2 pediatric conditions. A continuous high-frequency oscillation device integrated into the inspiratory limb of a conventional critical care ventilator was attached to an endotracheal tube (ETT) with a collection filter and test lung. High-frequency oscillation with high-flow setting was used with jet nebulizers attached to the manifold, and a vibrating mesh nebulizer placed between the ETT and the ventilator circuit versus at the inlet of the humidifier. Albuterol (2.5 mg in 3 mL) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: During continuous high-frequency oscillation, the mean inhaled dose with jet nebulizers was low (<2% with the adult settings and <1% with the pediatric settings). Across both adult and pediatric conditions, when the vibrating mesh nebulizer was placed between the ETT and the Y-piece during continuous high-frequency oscillation, the inhaled dose was higher than with the placement of the vibrating mesh nebulizer at the inlet of the humidifier, median 11.1% (IQR 7.0%-13.7%) median 6.0% (IQR 3.9%-7.2%) (P = .002) respectively, but still lower than the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier with continuous high-frequency oscillation off, median 22.7% (IQR 19.5%-25.4%) versus median 11.1% (IQR 7.0%-13.7%) (P < .001). The inhaled dose with the 10-year-old scenario was higher than with the 5-year-old scenario in all settings except aerosol delivery via continuous high-frequency oscillation. CONCLUSIONS: During invasive mechanical ventilation with continuous high-frequency oscillation, aerosol delivery with jet nebulizers in the manifold resulted in a marginal inhaled dose. The vibrating mesh nebulizer at the ETT during continuous high-frequency oscillation delivered 6-fold more aerosol than did the jet nebulizer, while delivering only half of the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier without continuous high-frequency oscillation.

Efficacy of Various Mitigation Devices in Reducing Fugitive Emissions from Nebulizers.

BACKGROUND: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. METHODS: Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 µm at baseline, before, during, and after each treatment. RESULTS: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 µm in size for VMN and 0.3-3.0 µm for SVN (all P < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 µm sized particle concentrations for SVN (all P < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type. CONCLUSIONS: SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice.

Mitigating Fugitive Aerosols During Aerosol Delivery via High-Flow Nasal Cannula Devices.

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown. METHODS: Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 µm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm. RESULTS: Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 µm particles (all P < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 µm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all P < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 µm particles (all P < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was ≥ 6 times higher than vibrating mesh nebulizer via Vapotherm. CONCLUSIONS: During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations.

Optimizing high-flow nasal cannula flow settings in adult hypoxemic patients based on peak inspiratory flow during tidal breathing.

BACKGROUND: Optimal flow settings during high-flow nasal cannula (HFNC) therapy are unknown. We investigated the optimal flow settings during HFNC therapy based on breathing pattern and tidal inspiratory flows in patients with acute hypoxemic respiratory failure (AHRF). METHODS: We conducted a prospective clinical study in adult hypoxemic patients treated by HFNC with a fraction of inspired oxygen (FIO2) ≥ 0.4. Patient's peak tidal inspiratory flow (PTIF) was measured and HFNC flows were set to match individual PTIF and then increased by 10 L/min every 5-10 min up to 60 L/min. FIO2 was titrated to maintain pulse oximetry (SpO2) of 90-97%. SpO2/FIO2, respiratory rate (RR), ROX index [(SpO2/FIO2)/RR], and patient comfort were recorded after 5-10 min on each setting. We also conducted an in vitro study to explore the relationship between the HFNC flows and the tracheal FIO2, peak inspiratory and expiratory pressures. RESULTS: Forty-nine patients aged 58.0 (SD 14.1) years were enrolled. At enrollment, HFNC flow was set at 45 (38, 50) L/min, with an FIO2 at 0.62 (0.16) to obtain an SpO2/FIO2 of 160 (40). Mean PTIF was 34 (9) L/min. An increase in HFNC flows up to two times of the individual patient's PTIF, incrementally improved oxygenation but the ROX index plateaued with HFNC flows of 1.34-1.67 times the individual PTIF. In the in vitro study, when the HFNC flow was set higher than PTIF, tracheal peak inspiratory and expiratory pressures increased as HFNC flow increased but the FIO2 did not change. CONCLUSION: Mean PTIF values in most patients with AHRF were between 30 and 40 L/min. We observed improvement in oxygenation with HFNC flows set above patient PTIF. Thus, a pragmatic approach to set optimal flows in patients with AHRF would be to initiate HFNC flow at 40 L/min and titrate the flow based on improvement in ROX index and patient tolerance. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03738345). Registered on November 13th, 2018. https://clinicaltrials.gov/ct2/show/NCT03738345?term=NCT03738345&draw=2&rank=1.

Aerosol particle concentrations with different oxygen devices and interfaces for spontaneous breathing patients with tracheostomy: a randomised crossover trial.

For stable spontaneously breathing tracheostomy patients with uncuffed airways, different humidification devices and interfaces did not generate clinically significant differences of aerosol particle concentrations https://bit.ly/2Y1HSO2.

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.

Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows.

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: In a randomized controlled trial, patients with a history of COPD or asthma and documented positive responses to inhaled bronchodilators in an outpatient pulmonary function laboratory were recruited. Subjects were randomized to receive inhalation at gas flow ratio settings of: GF:IF = 0.5, GF:IF = 1.0, or GF = 50 L/min. Subjects were assigned to inhale saline (control) followed by salbutamol via HFNC with cumulative doses of 0.5 mg, 1.5 mg, 3.5 mg, and 7.5 mg. Spirometry was performed at baseline and 10-12 min after each inhalation. (3) Results: 75 subjects (49 asthma and 26 COPD) demonstrating bronchodilator response were enrolled. Per the robust ATS/ERS criteria no difference was observed between flows, however using the criteria of post-bronchodilator forced expiratory volume in the first second (FEV1) reaching the screening post-bronchodilator FEV1 with salbutamol, a higher percentage of subjects receiving GF:IF = 0.5 met the criteria at a cumulative dose of 1.5 mg than those receiving GF:IF = 1.0, and GF = 50 L/min (64% vs. 29% vs. 27%, respectively, p = 0.011). Similarly at 3.5 mg (88% vs. 54% vs. 46%, respectively, p = 0.005). The effective dose at GF:IF = 0.5 was 1.5 mg while for GF = 50 L/min it was 3.5 mg. (4) Conclusions: During salbutamol delivery via HFNC, cumulative doses of 1.5 mg to 3.5 mg resulted in effective bronchodilation. Applying the robust ATS/ERS criteria no difference was observed between the flows, however using the more sensitive criteria of subjects reaching post screening FEV1 to salbutamol via HFNC, a higher number of subjects responded to the doses of 0.5 mg and 1.5 mg when HFNC gas flow was set at 50% of patient peak inspiratory flow.