Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model.

PURPOSE: Surfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation. METHODS: Juvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200 mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60 mg device loaded dose; equivalent to 24 mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30 min for 3.5 h and macro- and microscopy images were acquired at necropsy. RESULTS: While aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO2; 96-100% recovery) and oxygenation index, and the aerosol group had superior recovery of compliance (P < 0.05). The SLS-EEG aerosol group showed less lung tissue injury, greater uniformity in lung aeration, and more homogenous surfactant distribution at the alveolar surfaces compared with liquid Curosurf. CONCLUSIONS: The new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part I: In Vitro Testing and Characterization.

PURPOSE: Improving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments. METHODS: A new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals. RESULTS: The best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7-17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min. CONCLUSIONS: A high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.

Aerosol Delivery Efficiency With High-Flow Nasal Cannula Therapy in Neonatal, Pediatric, and Adult Nasal Upper-Airway and Lung Models.

BACKGROUND: High-flow nasal cannula (HFNC) systems employ different methods to provide aerosol to patients. This study compared delivery efficiency, particle size, and regional deposition of aerosolized bronchodilators during HFNC in neonatal, pediatric, and adult upper-airway and lung models between a proximal aerosol adapter and distal aerosol circuit chamber. METHODS: A filter was connected to the upper airway to a spontaneously breathing lung model. Albuterol was nebulized using the aerosol adapter and circuit at different clinical flow settings. The aerosol mass deposited in the upper airway and lung was quantified. Particle size was measured with a laser diffractometer. Regional deposition was assessed with a gamma camera at each nebulizer location and patient model with minimum flow settings. RESULTS: Inhaled lung doses ranged from 0.2-0.8% for neonates, 0.2-2.2% for the small child, and 0.5-5.2% for the adult models. Neonatal inhaled lung doses were not different between the aerosol circuit and adapter, but the aerosol circuit showed marginally greater lung doses in the pediatric and adult patient models. Impacted aerosols and condensation in the non-heated HFNC and aerosol delivery components contributed to the dispersion of coarse liquid droplets, high deposition (11-44%), and occlusion of the supine neonatal upper airway. In contrast, the upright pediatric and adult upper-airway models had minimal deposition (0.3-7.0%) and high fugitive losses (∼24%) from liquid droplets leaking out of the nose. The high impactive losses in the aerosol adapter (56%) were better contained than in the aerosol circuit, resulting in less cannula sputter (5% vs 22%), fewer fugitive losses (18% vs 24%), and smaller inhaled aerosols (5 µm vs 13 µm). CONCLUSIONS: The inhaled lung dose was low (1-5%) during HFNC. Approaches that streamline aerosol delivery are needed to provide safe and effective therapy to patients receiving aerosolized medications with this HFNC system.

In Vitro Comparison of Aerosol Delivery in High-Frequency Assisted Airway Clearance Devices With Integrated Nebulizers.

BACKGROUND: High-frequency assisted airway clearance systems combine positive expiratory pressure or oscillatory positive airway pressure with integrated nebulizers to improve the delivery of aerosols and assist with airway clearance. This aerosol study evaluated lung delivery efficiency during positive expiratory pressure and oscillatory positive airway pressure therapy of 2 high-frequency assisted airway clearance/nebulizer systems. METHODS: Aerosol delivery was evaluated during positive expiratory pressure therapy of 10 cm H2O and oscillatory positive airway pressure therapy of 20 cm H2O with the BiWaze Clear and the Volara high-frequency assisted airway clearance/nebulizer systems. The handset and nebulizer were attached to an anatomic upper-airway model via a mouthpiece and placed into a plethysmograph. A tracheal filter was placed to capture the inhaled aerosol. A vacuum filter entrained fugitive aerosols from the plethysmograph. After nebulization of technetium in 3.0 mL normal saline solution, the components were scanned by using scintigraphy and the decay-corrected radiation counts were referenced to the initial nebulizer technetium charges. RESULTS: Aerosol delivery during positive expiratory pressure therapy of 10 cm H2O resulted in higher lung deposition with the BiWaze Clear versus the Volara (28 vs 6.2%; P < .001; 95% CI 16.5-27.7), and higher fugitive losses (23.7 vs 2.8%; P = .004) and nebulizer losses (55 vs 3.3%; P < .001) with the Volara than with the BiWaze Clear. Aerosol delivery during oscillatory positive airway pressure of 20 cm H2O resulted in a higher lung deposition with the BiWaze Clear versus the Volara (16.3 vs 7.3%; P = .005; 95% CI 3.3-15) and higher fugitive (22.3 vs 3.8%; P = .02) and nebulizer (58.8 vs 7.2%; P = .004) losses with the Volara. There were no differences at the other locations during testing. CONCLUSIONS: The BiWaze Clear system showed greater delivery efficiency than did the Volara during positive expiratory pressure and oscillatory positive airway pressure. The high residual nebulizer dose and fugitive aerosol losses through the handset leak valve contributed to the lower delivery efficiency observed with the Volara. The nebulizer type, circuit design, and handset are important factors when targeting effective aerosol delivery to the lungs with high-frequency assisted airway clearance therapy.

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.

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.

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.

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.

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.

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.

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..

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.

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.

Physiologic Effects of Nasal Aspiration and Nasopharyngeal Suctioning on Infants With Viral Bronchiolitis.

BACKGROUND: There is limited evidence supporting an optimum method for removing mucus from the airways of hospitalized infants with bronchiolitis. This study was designed to evaluate short-term physiologic effects between nasal aspiration and nasopharyngeal suctioning in infants. METHODS: Sixteen infants requiring hospitalization for supportive management of bronchiolitis were instrumented with transcutaneously measured partial pressure of carbon dioxide ([Formula: see text]) and [Formula: see text] monitoring. Electrical impedance tomography (EIT) was used to estimate changes in inspiratory and end-expiratory lung volume loss and recovery. Subjects were suctioned with both nasal aspiration and nasopharyngeal suctioning methods in a randomized order (8 received nasal aspiration followed by nasopharyngeal suctioning, and 8 received nasophayrgeal suctioning followed by nasal aspiration). Noninvasive gas exchange and EIT measurements were obtained at baseline (pre-suction) and at 10, 20, and 30 min following each suctioning intervention. Sputum mass was obtained following suctioning, and clinical respiratory severity scores, before and after suctioning, were computed. RESULTS: There were no differences in inspiratory EIT (P = .93), change in end-expiratory lung impedance (ΔEELI; P = .53), [Formula: see text] (P = .41), [Formula: see text] (P = .88), heart rate (P = .31), or breathing frequency (P = .15) over the course of suctioning between nasal aspiration and nasopharyngeal suctioning. Sputum mass (P = .14) and clinical respiratory score differences before and after suctioning (P = .59) were not different between the 2 suctioning interventions. Sputum mass was not associated with ΔEELI at 30 min for nasal aspiration (ρ = 0.11, P = .69), but there was a moderate positive association for nasopharyngeal suctioning (ρ = 0.50, P = .048). CONCLUSIONS: Infants with viral bronchiolitis appeared to tolerate both suctioning techniques without adverse short-term physiologic effects, as indicated by the unchanged gas exchange and estimated lung volumes (EIT). Nasopharyngeal suctioning recovered 36% more sputum than did nasal aspiration and there was moderate correlation between sputum mass and end-expiratory lung impedance change at 30 minutes post-suction with nasopharyngeal that was not present with nasal aspiration. It is possible that a subset of patients may benefit from one type of suctioning over another. Future research focusing on important outcomes for suctioning patients with bronchiolitis with varying degrees of lung disease severity is needed.

Interaction of Critical Care Practitioners With a Decision Support Tool for Weaning Mechanical Ventilation in Children.

BACKGROUND: There is evidence that ventilator weaning protocols provide benefit to children receiving mechanical ventilation, but many protocols do not include explicit instructions for decreasing ventilator support from maximal settings. We evaluated care provider opinions on ventilator weaning recommendations made by a computerized decision support tool. METHODS: Recommendations for ventilator adjustment were generated using a computerized decision support tool based on the ARDSNet protocol using data from children with acute hypoxemic respiratory failure admitted to the pediatric ICU (PICU). Attending physicians, fellows, nurse practitioners, and respiratory therapists (RTs) caring for these patients answered a brief survey to assess whether recommendations were reasonable and whether the practitioner believed they could be implemented. RESULTS: RTs completed 99 surveys and ICU providers completed 96 surveys based on data from 10 patients. RTs and ICU providers found 63.9% and 65.3% of recommendations reasonable, respectively. There were 5 instances of disagreement between RTs and ICU providers. The percent of recommendations that RTs thought could be implemented was 29.9%, whereas this figure for ICU providers was 26.3%, with 4 instances of disagreement. Free-text responses indicated that many RTs and ICU providers were concerned about disrupting current patient stability and low tidal volumes. CONCLUSIONS: On initial evaluation, the decision support tool did not appear to be highly acceptable to RTs and ICU providers in our setting because recommendations were rarely implemented. In addition, acceptability did not increase over time as patients generally improved. Most respondents preferred to make no ventilator changes and felt the recommendations were too aggressive. The notable barrier to use was a perception of potential patient instability with weaning.

Decreasing radiographs in neonates through targeted quality improvement interventions.

OBJECTIVE: Our aim was to decrease radiograph use for monitoring placement of peripherally inserted central catheters (PICC) and endotracheal tubes (ETT) in neonates admitted to the neonatal intensive care unit (NICU) by 20% from November 2017 to November 2018. STUDY DESIGN: We carried out three Plan-Do-Study-Act (PDSA) cycles: (1) implementation of a radiograph protocol emphasizing ideal patient positioning, standard radiograph views and frequency, (2) standardizing ETT depth using the NRP guidelines, and (3) implementation of an institution specific ETT depth guideline. RESULTS: The pre-intervention radiographs per PICC day was 0.86 versus a post-intervention value of 0.46 (P = 0.004). The pre-intervention radiographs per ETT day was 1.45 versus a post-intervention value of 1.07 (P = 0.002). CONCLUSIONS: Our multidisciplinary NICU team performed a QI project, which resulted in more than a 20% decrease in the number of radiographs used for monitoring placement of PICCs and ETTs.

Physiologic Effects of 3 Different Neonatal Volume-Targeted Ventilation Modes in Surfactant-Deficient Juvenile Rabbits.

BACKGROUND: Different brands of volume-targeted modes may vary the location of tidal volume (VT) monitoring and whether peak inspiratory pressure is adjusted based on inspiratory, expiratory, or leak-compensated VT. These variables may result in different levels of support provided to patients, especially when an endotracheal tube (ETT) leak is present. We hypothesized that there would be no differences in gas exchange, triggering, or work of breathing between volume-targeted modes of 3 different brands of equipment in a surfactant-deficient, spontaneously breathing animal model with and without an ETT leak. METHODS: Twelve rabbits (mean ± SD 1.61 ± 0.20 kg) were sedated, anesthetized, intubated, lavaged with 0.9% saline solution, and randomized in a crossover design so that each animal was supported by 3 different volume-targeted modes at identical settings with and without an ETT leak. After 30 min, arterial blood gas, VT, and esophageal and airway pressure were recorded for each condition, and pressure-rate product and percentage of successfully triggered breaths were calculated. RESULTS: Gas exchange and the pressure-rate product were not different between the ventilators in the absence of an ETT leak. When an ETT leak was introduced, volume-guarantee modes allowed a higher percentage of triggered breaths and peak inspiratory pressure, which resulted in higher minute ventilation, pH, and lower PaCO2 than the pressure-regulated volume control mode (P < .05). CONCLUSIONS: When a moderate ETT leak was present, volume-targeted modes that used proximal VT monitoring and triggering with adaptive leak compensation capabilities appeared more effective in providing ventilation support than did a ventilator that used measurements obtained from the back at the ventilator and does not have leak compensation.