Efficacy, dose-response, and aerosol delivery of dry powder synthetic lung surfactant treatment in surfactant-deficient rabbits and premature lambs.

BACKGROUND: Dry powder (DP) synthetic lung surfactant may be an effective means of noninvasive delivery of surfactant therapy to premature infants supported with nasal continuous positive airway pressure (nCPAP) in low-resource settings. METHODS: Four experimental DP surfactant formulations consisting of 70% of phospholipids (DPPC:POPG 7:3), 3% Super Mini-B (SMB) or its sulfur-free derivate B-YL as SP-B peptide mimic, 25% of lactose or trehalose as excipient, and 2% of NaCl were formulated using spray drying. In vitro surface activity was confirmed with captive bubble surfactometry. Surfactant particle size was determined with a cascade impactor and inhaled dose was quantified using a spontaneously breathing premature lamb lung model supported with CPAP. In vivo surfactant efficacy was demonstrated in three studies. First, oxygenation and lung compliance were monitored after intratracheal instillation of resuspended DP surfactant in intubated, ventilated, lavaged, surfactant-deficient juvenile rabbits. In dose-response studies, ventilated, lavaged, surfactant-deficient rabbits received 30, 60, 120 or 240 mg/kg of DP B-YL:Lactose or B-YL:Trehalose surfactant by aerosol delivery with a low flow aerosol chamber via their endotracheal tube. Noninvasive aerosolization of DP B-YL:Trehalose surfactant via nasal prongs was tested in spontaneous breathing premature lambs supported with nCPAP. Intratracheal administration of 200 mg/kg of Curosurf®, a liquid porcine surfactant, was used as a positive control. RESULTS: Mass median aerosol diameter was 3.6 µm with a geometric standard deviation of 1.8. All four experimental surfactants demonstrated high surface efficacy of intratracheal instillation of a bolus of ~ 100 mg/kg of surfactant with improvement of oxygenation and lung compliance. In the dose-response studies, rabbits received incremental doses of DP B-YL:Lactose or B-YL:Trehalose surfactant intratracheally and showed an optimal response in oxygenation and lung function at a dose of 120-240 mg/kg. Aerosol delivery via nasal prongs of 1 or 2 doses of ~ 100 mg/kg of B-YL:Trehalose surfactant to premature lambs supported with nCPAP resulted in stabilization of spontaneous breathing and oxygenation and lung volumes comparable to the positive control. CONCLUSION: These studies confirm the clinical potential of DP synthetic lung surfactant with B-YL peptide as a SP-B mimic to alleviate surfactant deficiency when delivered as a liquid bolus or as an aerosol.

Postextubation Noninvasive Ventilation in Respiratory Distress Syndrome: A Randomized Controlled Trial.

OBJECTIVE: Successful extubation and prevention of reintubation remain primary goals in neonatal ventilation. Our aim was to compare three modalities of postextubation respiratory support-noninvasive positive pressure ventilation (NIPPV), nasal bilevel positive airway pressure (N-BiPAP), and nasal continuous positive airway pressure (NCPAP)-using the RAM cannula in preterm neonates with respiratory distress syndrome (RDS). Our secondary aim was to define the predictors of successful extubation. STUDY DESIGN: A total of 120 preterm neonates (gestational age ≤35 weeks) with RDS who had undergone primary invasive ventilation were randomized to receive either NIPPV, N-BiPAP, or NCPAP. The incidence of respiratory failure in the first 48 hours postextubation, total days of invasive and noninvasive ventilation, duration of hospitalization, and mortality were measured and compared among the three different noninvasive support modalities. RESULTS: There were no significant differences in the postextubation respiratory failure rates and the number of days of invasive as well as noninvasive ventilation among the three different support modalities (p > 0.05). The total number of days of mechanical ventilation and the duration of hospitalization were significantly higher in the N-BiPAP group than those in the NCPAP or NIPPV groups (p < 0.05). A gestational age of at least 29 weeks and a birth weight of at least 1.4 kg were predictive of successful extubation with a sensitivity of 98.2 and 85.3% and a specificity of 63.6 and 90.9%, respectively. CONCLUSION: Longer durations of mechanical ventilation and hospitalization were observed with N-BiPAP as a noninvasive mode of ventilation, but there was no significant difference in the extubation failure rates among the three modalities. Gestational age and birth weight were shown to be independent predictors of successful extubation of preterm neonates with RDS. KEY POINTS: · Successful extubation and reintubation prevention of preterms are primary goals in neonatal ventilation.. · NIPPV, N-BiPAP, and NCPAP could be used as postextubation noninvasive modes in preterm neonates.. · Gestational age and birth weight are independent predictors of successful extubation of preterms..

Characterizing the Effects of Nasal Prong Interfaces on Aerosol Deposition in a Preterm Infant Nasal Model.

The objective of this study was to characterize the effects of multiple nasal prong interface configurations on nasal depositional loss of pharmaceutical aerosols in a preterm infant nose-throat (NT) airway model. Benchmark in vitro experiments were performed in which a spray-dried powder formulation was delivered to a new preterm NT model with a positive-pressure infant air-jet dry powder inhaler using single- and dual-prong interfaces. These results were used to develop and validate a computational fluid dynamics (CFD) model of aerosol transport and deposition in the NT geometry. The validated CFD model was then used to explore the NT depositional characteristic of multiple prong types and configurations. The CFD model highlighted a turbulent jet effect emanating from the prong(s). Analysis of NT aerosol deposition efficiency curves for a characteristic particle size and delivery flowrate (3 µm and 1.4 L/min (LPM)) revealed little difference in NT aerosol deposition fraction (DF) across the prong insertion depths of 2-5 mm (DF = 16-24%) with the exception of a single prong with 5-mm insertion (DF = 36%). Dual prongs provided a modest reduction in deposition vs. a single aerosol delivery prong at the same flow for insertion depths < 5 mm. The presence of the prongs increased nasal depositional loss by absolute differences in the range of 20-70% compared with existing correlations for ambient aerosols. In conclusion, the use of nasal prongs was shown to have a significant impact on infant NT aerosol depositional loss prompting the need for prong design alterations to improve lung delivery efficiency.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

Humidification of Blow-By Oxygen During Recovery of Postoperative Pediatric Patients: One Unit's Journey.

PURPOSE: To examine the practice of nebulizer cool mist blow-by oxygen administered to spontaneously breathing postanesthesia care unit (PACU) pediatric patients during Phase one recovery. DESIGN: Existing evidence was evaluated. Informal benchmarking documented practices in peer organizations. An in vitro study was then conducted to simulate clinical practice and determine depth and amount of airway humidity delivery with blow-by oxygen. METHODS: Informal benchmarking information was obtained by telephone interview. Using a three-dimensional printed simulation model of the head connected to a breathing lung simulator, depth and amount of moisture delivery in the respiratory tree were measured. FINDINGS: Evidence specific to PACU administration of cool mist blow-by oxygen was limited. Informal benchmarking revealed that routine cool mist oxygenated blow-by administration was not widely practiced. The laboratory experiment revealed minimal moisture reaching the mid-tracheal area of the simulated airway model. CONCLUSIONS: Routine use of oxygenated cool mist in spontaneously breathing pediatric PACU patients is not supported.

A pilot study to assess short-term physiologic outcomes of transitioning infants with severe bronchopulmonary dysplasia from ICU to two subacute ventilators.

INTRODUCTION: This study was designed to evaluate short-term physiologic outcomes of transitioning neonates with bronchopulmonary dysplasia (BPD) from intensive care unit (ICU) ventilators to both the Trilogy 202 (Philips Healthcare, Andover, MA) and LTV 1200 (CareFusion, Yorba Linda, CA) subacute ventilators. METHODS: Six infants with BPD requiring tracheostomies for support with a neonatal-specific ICU ventilator underwent placement of esophageal balloon catheters, airway pressure transducers, flow sensors, oxygen saturation (SpO2), and end tidal carbon dioxide (PETCO2) monitors. Noninvasive gas exchange, airflow, and airway and esophageal pressures (PES) were recorded following 20 min on the ICU ventilator. The infants were placed on the Trilogy 202 and LTV 1200 ventilators in random order at identical settings as the ICU ventilator. We measured noninvasive gas exchange, pressure-rate product (respiratory rate × ΔPES), ventilator response times, and the percentage of spontaneous breaths that triggered the ventilator at 20 min in each subject while being supported with each of the different subacute ventilators. RESULTS: The mean (SD) weight of the six infants was 4.983 (0.56) kg. There were no differences in heart rate (p = 0.51) or SpO2 (p = 0.97) but lower PETCO2, ΔPES, respiratory rate, pressure rate-product, response times, and greater percentage of subject initiated breaths that triggered the ventilator (p < 0.05) was observed with the Trilogy 202 than the LTV 1200. All six infants transitioned successfully from the ICU ventilator to the Trilogy 202 ventilator. CONCLUSION: In this small group of infants with BPD, the Trilogy 202 ventilator performed better than the LTV 1200. The improved subject efforts, per cent subject triggering, and response times observed with the Trilogy are likely related to differences in triggering algorithms, location of triggering mechanisms, and gas delivery system performance within the ventilators. These pilot data may be useful for informing future clinical study design and understanding differences in the level of support provided by different subacute ventilators in infants with BPD.

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

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.

Evaluation of lung volumes and gas exchange in surfactant-deficient rabbits between variable and fixed servo pressures during high-frequency jet ventilation.

OBJECTIVE: To investigate a novel servo pressure (SP) setting during high-frequency jet ventilation (HFJV) for a lung protective strategy in a neonatal model of acute respiratory distress. STUDY DESIGN: Comparison of efficacy between variable (standard) and fixed SP settings in a randomized animal study using rabbits (n = 10, mean weight = 1.80 kg) with surfactant deficiency by repeated lung lavages. RESULTS: Rabbits in the fixed SP group had greater peak inspiratory pressure, SP, minute volume, pH, and PaO2, and lower PaCO2 after lung lavage than the variable SP group. Lung volume monitoring with electrical impedance tomography showed that fixed SP reduced the decline of the global lung tidal variation at 30 min after lung lavage (-17.4% from baseline before lavage) compared to variable SP (-44.9%). CONCLUSION: HFJV with fixed SP significantly improved gas exchange and lung volumes compared to variable SP. Applying a fixed SP may have important clinical implications for patients receiving HFJV.

In vitro-in vivocorrelation of aerosol deposition before and after metered-dose inhaler coaching in healthy children.

Although pressurized metered dose inhaler (pMDI) education is a routine part of childhood asthma management and encouraging 'optimal breathing patterns' (i.e. slowly, deeply, completely, and with a mouth seal on the mouthpiece) is an integral part of recommended pMDI education, there is currently no quantifiable way to determine if a child is inhaling their medication correctly or optimally through a valved holding chamber (VHC). The TipsHaler™ (tVHC) is a prototype VHC device that measures inspiratory time, flow, and volume without changing the properties of the medication aerosol. The measurementsin vivorecorded by the tVHC can be downloaded and transferred to a spontaneous breathing lung model to simulate the inhalational patternsin vitroand also determine the deposition of inhaled aerosol mass with each pattern. We hypothesized that pediatric patients' inhalational patterns when using a pMDI would improve after active coaching via tVHC. This would increase the pulmonary deposition of inhaled aerosols in anin vitromodel. To test this hypothesis, we conducted a single-site, prospective, pilot, pre-and-post intervention study paired with a bedside-to-bench experiment. Healthy, inhaler-naïve subjects used a placebo inhaler in conjunction with the tVHC before and after coaching and recorded inspiratory parameters. These recordings were then implemented into a spontaneous breathing lung model during albuterol MDI delivery, and pulmonary deposition of albuterol was quantified. In this pilot study, active coaching resulted in a statistically significant increase in inspiratory time (n= 8,p= 0.0344, 95%CI: 0.082 to ∞). tVHC recorded inspiratory parameters obtained from patients were successfully implemented in thein vitromodel, which demonstrated that both inspiratory time (n= 8,r= 0.78,p <0.001, 95%CI: 0.47-0.92) and volume (n= 8,r= 0.58,p =0.0186, 95%CI: 0.15-0.85) strongly correlate with pulmonary deposition of inhaled drugs.

Evaluation of a Novel Dry Powder Surfactant Aerosol Delivery System for Use in Premature Infants Supported with Bubble CPAP.

Aerosolized lung surfactant therapy during nasal continuous positive airway pressure (CPAP) support avoids intubation but is highly complex, with reported poor nebulizer efficiency and low pulmonary deposition. The study objective was to evaluate particle size, operational compatibility, and drug delivery efficiency with various nasal CPAP interfaces and gas humidity levels of a synthetic dry powder (DP) surfactant aerosol delivered by a low-flow aerosol chamber (LFAC) inhaler combined with bubble nasal CPAP (bCPAP). A particle impactor characterized DP surfactant aerosol particle size. Lung pressures and volumes were measured in a preterm infant nasal airway and lung model using LFAC flow injection into the bCPAP system with different nasal prongs. The LFAC was combined with bCPAP and a non-heated passover humidifier. DP surfactant mass deposition within the nasal airway and lung was quantified for different interfaces. Finally, surfactant aerosol therapy was investigated using select interfaces and bCPAP gas humidification by active heating. Surfactant aerosol particle size was 3.68 µm. Lung pressures and volumes were within an acceptable range for lung protection with LFAC actuation and bCPAP. Aerosol delivery of DP surfactant resulted in variable nasal airway (0-20%) and lung (0-40%) deposition. DP lung surfactant aerosols agglomerated in the prongs and nasal airways with significant reductions in lung delivery during active humidification of bCPAP gas. Our findings show high-efficiency delivery of small, synthetic DP surfactant particles without increasing the potential risk for lung injury during concurrent aerosol delivery and bCPAP with passive humidification. Specialized prongs adapted to minimize extrapulmonary aerosol losses and nasal deposition showed the greatest lung deposition. The use of heated, humidified bCPAP gases compromised drug delivery and safety. Safety and efficacy of DP aerosol delivery in preterm infants supported with bCPAP requires more research.

Performance Characteristics of a Novel 3D-Printed Bubble Intermittent Mandatory Ventilator (B-IMV) for Adult Pulmonary Support.

The COVID-19 pandemic has brought attention to the need for developing effective respiratory support that can be rapidly implemented during critical surge capacity scenarios in healthcare settings. Lung support with bubble continuous positive airway pressure (B-CPAP) is a well-established therapeutic approach for supporting neonatal patients. However, the effectiveness of B-CPAP in larger pediatric and adult patients has not been addressed. Using similar principles of B-CPAP pressure generation, application of intermittent positive pressure inflations above CPAP could support gas exchange and high work of breathing levels in larger patients experiencing more severe forms of respiratory failure. This report describes the design and performance characteristics of the BubbleVent, a novel 3D-printed valve system that combined with commonly found tubes, hoses, and connectors can provide intermittent mandatory ventilation (IMV) suitable for adult mechanical ventilation without direct electrification. Testing of the BubbleVent was performed on a passive adult test lung model and compared with a critical care ventilator commonly used in tertiary care centers. The BubbleVent was shown to deliver stable PIP and PEEP levels, as well as timing control of breath delivery that was comparable with a critical care ventilator.

Neonatal noninvasive ventilation techniques: do we really need to intubate?

The current trend for supporting neonates with respiratory distress syndrome is nasal continuous positive airway pressure (CPAP). Nearly half of all neonates who are supported with CPAP will still develop respiratory failure that requires potentially injurious endotracheal intubation and invasive ventilation. Thus, the role of any neonatal clinician is to minimize invasive ventilation whenever possible, to avoid the multitude of complications that can arise when using this form of therapy. Noninvasive ventilation (NIV) is a form of respiratory assistance that provides greater respiratory support than does CPAP and may prevent intubation in a larger fraction of neonates who would otherwise fail CPAP. With the inception of nasal airway interfaces, clinicians have ushered in many different forms of NIV in neonates, often with very little experimental data to guide management. This review will explore in detail all of the different forms of neonatal NIV that are currently focused within an area of intense clinical investigation.

Mechanical ventilation of the premature neonate.

Although the trend in the neonatal intensive care unit is to use noninvasive ventilation whenever possible, invasive ventilation is still often necessary for supporting pre-term neonates with lung disease. Many different ventilation modes and ventilation strategies are available to assist with the optimization of mechanical ventilation and prevention of ventilator-induced lung injury. Patient-triggered ventilation is favored over machine-triggered forms of invasive ventilation for improving gas exchange and patient-ventilator interaction. However, no studies have shown that patient-triggered ventilation improves mortality or morbidity in premature neonates. A promising new form of patient-triggered ventilation, neurally adjusted ventilatory assist (NAVA), was recently FDA approved for invasive and noninvasive ventilation. Clinical trials are underway to evaluate outcomes in neonates who receive NAVA. New evidence suggests that volume-targeted ventilation modes (ie, volume control or pressure control with adaptive targeting) may provide better lung protection than traditional pressure control modes. Several volume-targeted modes that provide accurate tidal volume delivery in the face of a large endotracheal tube leak were recently introduced to the clinical setting. There is ongoing debate about whether neonates should be managed invasively with high-frequency ventilation or conventional ventilation at birth. The majority of clinical trials performed to date have compared high-frequency ventilation to pressure control modes. Future trials with premature neonates should compare high-frequency ventilation to conventional ventilation with volume-targeted modes. Over the last decade many new promising approaches to lung-protective ventilation have evolved. The key to protecting the neonatal lung during mechanical ventilation is optimizing lung volume and limiting excessive lung expansion, by applying appropriate PEEP and using shorter inspiratory time, smaller tidal volume (4-6 mL/kg), and permissive hypercapnia. This paper reviews new and established neonatal ventilation modes and strategies and evaluates their impact on neonatal outcomes.

Neonatal and pediatric respiratory care: what does the future hold?

Neonatal and pediatric respiratory care continues to move forward at a truly impressive pace. Recent technologic advances and an increasing number of randomized clinical trials are leading to improved outcomes for neonates, infants, children, and adolescents with respiratory illness. The goals of this 47th Respiratory Care Journal Conference were to review pertinent recent advances in neonatal and pediatric respiratory care and, more importantly, to offer thoughts and perspectives for the future of our field. It is important to note that of the prior 46 Journal Conferences, only 2 have been dedicated to neonatal and/or pediatric respiratory care topics. It is our hope that the publication of these proceedings will provide respiratory therapists, physicians, and other members of the clinical care team a foundation on which to ponder the future of neonatal and pediatric respiratory care.

Respiratory care year in review 2010: part 2. Invasive mechanical ventilation, noninvasive ventilation, pediatric mechanical ventilation, aerosol therapy.

The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting ß-adrenergic agents, long-acting ß-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting ß-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.

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.

Evaluation of a Bubble CPAP System for Low Resource Settings.

BACKGROUND: Despite its established safety, efficacy, and relative simplicity, CPAP treatment is not widely available for newborns and infants in low- and middle-income settings. A novel bubble CPAP system was designed to address the gaps in quality and accessibility of existing CPAP systems by providing blended, humidified, and pressurized gases without the need for electricity, compressed air, or manual power. This was the first study that tested the performance of the system with a simulated patient model. METHODS: In a spontaneously breathing 3-dimensional printed nasal airway model of a preterm neonate, CPAP performance was assessed based on delivered pressure, oxygen level, and humidity at different settings. RESULTS: Preliminary device performance characteristics were within 5% among 3 separate devices. Performance testing showed accurate control of CPAP and oxygen concentration at all settings with the bubble CPAP system. Lung model pressure and oxygen concentration were shown to stay within ±0.5 cm H2O and ±4% of full scale of the device settings, respectively, with relative humidity > 80%. CONCLUSIONS: Performance testing of the bubble CPAP system demonstrated accurate control of CPAP and oxygen concentration with humidity levels suitable for premature newborns on noninvasive support.

Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome.

OBJECTIVES: Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model. DESIGN: Preclinical study. SETTING: Research laboratory. SUBJECTS: Anesthetized pigs. INTERVENTION: In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation. MEASUREMENTS AND MAIN RESULTS: Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups. CONCLUSIONS: Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Effective gas exchange in paralyzed juvenile rabbits using simple, inexpensive respiratory support devices.

We have developed two devices: a high-amplitude bubble continuous positive airway pressure (HAB-CPAP) and an inexpensive bubble intermittent mandatory ventilator (B-IMV) to test the hypotheses that simple, inexpensive devices can provide gas exchange similar to that of bubble CPAP (B-CPAP) and conventional mechanical ventilation (CMV). Twelve paralyzed juvenile rabbits were intubated, stabilized on CMV, and then switched to CPAP. On identical mean airway pressures (MAPs), animals were unable to maintain pulse oximeter oxygen saturation (SpO2) >80% on conventional B-CPAP, but all animals oxygenated well (97.3 ± 2.1%) on HAB-CPAP. In fact, arterial partial pressures of O2 (Pao2) were higher during HAB-CPAP than during CMV (p = 0.01). After repeated lung lavages, arterial partial pressures of CO2 (Paco2) were lower with B-IMV than with CMV (p < 0.0001), despite identical ventilator settings. In lavaged animals, when HAB-CPAP was compared with CMV at the same MAP and 100% O2, no differences were observed in Pao2, but Paco2 levels were higher with HAB-CPAP (70 ± 7 versus 50 ± 5 mm Hg; p < 0.05). Arterial blood pressures were not impaired by HAB-CPAP or B-IMV. The results confirm that simple inexpensive devices can provide respiratory support in the face of severe lung disease and could extend the use of respiratory support for preterm infants into severely resource-limited settings.

Noninvasive respiratory support of juvenile rabbits by high-amplitude bubble continuous positive airway pressure.

Bubble continuous positive airway pressure (B-CPAP) applies small-amplitude, high-frequency oscillations in airway pressure (DeltaPaw) that may improve gas exchange in infants with respiratory disease. We developed a device, high-amplitude B-CPAP (HAB-CPAP), which provides greater DeltaPaw than B-CPAP provides. We studied the effects of different operational parameters on DeltaPaw and volumes of gas delivered to a mechanical infant lung model. In vivo studies tested the hypothesis that HAB-CPAP provides noninvasive respiratory support greater than that provided by B-CPAP. Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP. The animals were then supported at the same mean airway pressure, bias flow, and fraction of inspired oxygen (FiO2) required for stabilization, whereas the bubbler angle was varied in a randomized crossover design at exit angles, relative to vertical, of 0 (HAB-CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90), and 135 degrees (HAB-CPAP135). Arterial blood gases and pressure-rate product (PRP) were measured after 15 min at each bubbler angle. Pao2 levels were higher (p<0.007) with HAB-CPAP135 than with conventional B-CPAP. PaCO2 levels did not differ (p=0.073) among the three bubbler configurations. PRP with HAB-CPAP135 were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p=0.001). These results indicate that HAB-CPAP135 provides greater respiratory support than conventional B-CPAP does.