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.

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.

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.

Neonatal Jaundice: Improved Quality and Cost Savings After Implementation of a Standard Pathway.

OBJECTIVES: Seattle Children's Hospital sought to optimize the value equation for neonatal jaundice patients by creating a standard care pathway. METHODS: An evidence-based pathway for management of neonatal jaundice was created. This included multidisciplinary team assembly, comprehensive literature review, creation of a treatment algorithm and computer order sets, formulation of goals and metrics, roll-out of an education program for end users, and ongoing pathway improvement. The pathway was implemented on May 31, 2012. Quality metrics before and after implementation were compared. External data were used to analyze cost impacts. RESULTS: Significant improvements were achieved across multiple quality dimensions. Time to recovery decreased: mean length of stay was 1.30 days for 117 prepathway patients compared with 0.87 days for 69 postpathway patients (P < .001). Efficiency was enhanced: mean time to phototherapy initiation was 101.26 minutes for 14 prepathway patients compared with 54.67 minutes for 67 postpathway patients (P = .03). Care was less invasive: intravenous fluid orders were reduced from 80% to 44% (P < .001). Inpatient use was reduced: 66% of prepathway patients were admitted from the emergency department to inpatient care, compared with 50% of postpathway patients (P = .01). There was no increase in the readmission rate. These achievements translated to statistically significant cost reductions in total charges, as well as in the following categories: intravenous fluids, laboratory, room cost, and emergency department charges. CONCLUSIONS: An evidence-based standard care pathway for neonatal jaundice can significantly improve multiple dimensions of value, including reductions in cost and length of stay.