Background:

Nebulized therapy is commonly used in spontaneously breathing tracheostomized patients despite lack of recommended devices and techniques. We compared albuterol dose delivered toa model of spontaneously breathing children with tracheostomy using different nebulizers, tracheostomy tube sizes, inhalation techniques, and breathing patterns.

Methods:

A tracheostomy model was connected in series to a breathing simulator with a filter interposed. Breathing patterns of a 16 month old and 12-year old child and tracheostomytubes with internal diameters (mm) of 3.5, and 5.5 were used. Albuterol nebulizer solution (2.5 mg/3 ml) was used. A breath enhanced (BEN), a breath actuated (BAN), and a continuously operated nebulizer (CON) wereoperated for 5 minutes and run at 6 L/min with wall air. The latter was tested with different interfaces (T-piece and mask),with an extension tube and operated with and without assisted technique (every breath and every other breath). The amount of albuterol delivered was analyzed via spectrophotometry (276 nm). Particle size distribution was analyzed with a cooled Next Generation Impactor.

Results:

BEN was more efficient than others. Assisted technique for CON with extension increased albuterol delivery with every other breath (second best device/configuration) being superior to every breath technique. Adding an extension tube increased delivered albuterol. A T-piece was more efficient than a mask. Breathing patterns with larger Vt increased albuterol delivery. Tracheostomy size had less impact on drug delivery. Mass median aerodynamic diameter decreased between 48% and 74% when passing to the tracheostomies.0.8% of the nominal dose was deposited in the tracheostomy tube.

Conclusions:

The amount of albuterol delivered to a model of spontaneously breathing children with tracheostomyis influence by type of device and its configuration, use of assisted delivery, breathing pattern and tracheostomy size. Aerosols significantly decrease in size after passing through the tracheostomy tube.

Abstract

Background:

Early studies have found better clinical efficiency when a nebulizer was used with noninvasive positive pressure ventilation (NPPV), compared with spontaneous breathing without NPPV. However, very limited research addressed factors that might affect aerosol delivery. This study aimed to investigate the influence of exhalation valves and nebulizer positions on aerosol delivery during NPPV.

Methods:

We determined the efficiency of aerosol delivery in patients receiving NPPV with a lung model that simulates spontaneous breathing. Single-arch exhalation port, plateau exhalation valve, and whisper swivel were chosen as exhalation valves under different levels of inspiratory and expiratory pressures. A nebulizer was filled with 1 mL of 0.5% albuterol solution in 3 mL of normal saline, driven with 8 L/min oxygen, and placed at either a proximal position in the ventilator circuit (near the ventilator outlet, where humidifiers are usually connected) or a distal position in the ventilator circuit (between exhalation valve and lung model connection). Albuterol was collected by filters and then measured by ultraviolet spectrophotometry. The velocities of gas flow were also measured at different nebulizer positions.

Results:

Significant differences in the gas flow velocity were shown between proximal and distal positions of the breathing circuit under four combinations of inspiratory and expiratory pressure levels (15/5, 15/10, 25/5, and 25/10 cmH2O) (p<0.05). When the nebulizer was positioned distally, the single-arch exhalation port had the highest aerosol delivery, and the whisper swivel had the lowest aerosol delivery (p<0.05). When the nebulizer was placed proximally, the single-arch exhalation port had lower efficiency of aerosol delivery than the whisper swivel and plateau exhalation valve (p<0.05). In addition, higher inspiratory pressure was associated with increased aerosol delivery (p<0.05). The influence of expiratory pressure on aerosol delivery appeared too complex to predict.

Conclusions:

The type of exhalation valve and the position of the nebulizer in the ventilator circuit have a significant influence on the efficiency of aerosol delivery during NPPV. As a result, with different exhalation valves, an appropriate nebulizer position should be carefully chosen, and the inhaled dose should be adjusted after accurate prediction of aerosol delivery to ensure optimal clinical efficacy.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and its treatment is critical to improve quality of life, reduce symptoms, and diminish the frequency of COPD exacerbations. Due to the harmful environmental effects of pressurized metered-dose inhalers (pMDIs) containing chlorofluorocarbons (CFCs), newer systems for delivering respiratory medications have been developed.A search of the literature in the PubMed database was undertaken using the keywords "COPD," "albuterol," "ipratropium bromide," and "Respimat® Soft Mist Inhaler™"; pertinent references within the identified citations were included. The environmental effect of CFC-pMDIs, the invention of the Respimat® Soft Mist Inhaler™ (SMI) (Boehringer Ingelheim, Ingelheim, Germany), and its use to deliver the combination of albuterol and ipratropium bromide for the treatment of COPD were reviewed.The adverse environmental effects of CFC-pMDIs stimulated the invention of novel delivery systems including the Respimat SMI. This review presents its development, internal mechanism, and use to deliver the combination of albuterol and ipratropium bromide.CFC-pMDIs contributed to the depletion of the ozone layer and the surge in disorders caused by harmful ultraviolet B radiation. The banning of CFCs spurred the development of novel delivery systems for respiratory medications. The Respimat SMI is an innovative device that produces a vapor of inhalable droplets with reduced velocity and prolonged aerosol duration that enhance deposition within the lower airway and is associated with improved patient satisfaction. Clinical trials have demonstrated that the Respimat SMI can achieve effects equivalent to pMDIs but with lower medication doses. The long-term safety and efficacy remain to be determined. The Respimat SMI delivery device is a novel, efficient, and well-received system for the delivery of aerosolized albuterol and ipratropium bromide to patients with COPD; however, the presence of longer-acting, less frequently dosed respiratory medications provide patients and providers with other therapeutic options.

Ipratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant.The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A).This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A.Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers.PATIENTS WERE RANDOMIZED TO RECEIVE: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID.Patient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events.PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar. Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22). Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005). The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups.CVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device.

BACKGROND: The amygdala is the key brain structure for anxiety and emotional memory storage. We examined the involvement of β-adrenoreceptors in the basolateral amygdala (BLA) and their interaction with morphine in modulating these behaviors.The elevated plus-maze has been employed for investigating anxiety and memory. Male Wistar rats were used for this test. We injected morphine (4, 5, and 6 mg/kg) intraperitoneally, while salbutamol (albuterol) (1, 2, and 4 μg/rat) and propranolol (1, 2, and 4 μg/rat) were injected into the BLA. Open- arms time percentage (%OAT), open- arms entry percentage (%OAE), and locomotor activity were determined by this behavioral test. Retention was tested 24 hours later.Intraperitoneal injection of morphine (6 mg/kg) had an anxiolytic-like effect and improvement of memory. The highest dose of salbutamol decreased the anxiety parameters in test session and improved the memory in retest session. Coadministration of salbutamol and ineffective dose of morphine presenting anxiolytic response. In this case, the memory was improved. Intra-BLA administration of propranolol (4 μg/rat) decreased %OAT in the test session, while had no effect on memory formation. Coadministration of propranolol and morphine (6 mg/kg) showed an increase in %OAT. There was not any significant change in the above- mentioned parameter in the retest session. Coadministration of morphine and propranolol with the effective dose of salbutamol showed that propranolol could reverse anxiolytic-like effect. We found that opioidergic and β-adrenergic systems have the same effects on anxiety and memory in the BLA; but these effects are independent of each other.

OBJECTIVE::

We investigated the in vitro inspired dose and particle size distribution of albuterol delivered by a vibrating mesh nebulizer through the Vapotherm (Stevensville, MD) humidified high-flow nasal cannula system.

DESIGN:

: Albuterol (2.5mg/3mL) was delivered by an Aeroneb Solo (Aerogen, Galway, Ireland) nebulizer that was connected via adaptor proximal to the nasal cannula and downstream from the Vapotherm 2000i. Albuterol was collected onto an inspiratory filter mounted to a breath simulator programmed with age-appropriate breathing patterns. Particle sizing was completed by cascade impaction. Albuterol was quantified using ultraviolet spectrometry. Measurements were made using varying flow rates through infant, pediatric, and adult nasal cannulae.

SETTING:

: Aerosol research laboratory.

MEASUREMENTS AND MAIN RESULTS:

: The inspired dose (percent of nominal dose) for each cannula size and flow rate was 2.5%, 0.8%, 0.4%, and 0.2% for the adult cannula at 5, 10, 20, and 40 L/min, respectively; 1.2%, 0.6%, 0.1%, and 0.0% for the pediatric cannula at 3, 5, 10, and 20 L/min, respectively; and 0.6%, 0.6%, and 0.5% for the infant cannula at 3, 5, and 8 L/min, respectively. Most (62-80%) of the loaded albuterol dose accumulated within the adaptor. For each cannula size, there was a significant decrease in the inspired dose with increasing flow rates, p = 0.026 (infant), p = 0.001 (pediatric), and p < 0.001(adult). The inspired dose increased with increasing cannula size for 5, 10, and 20 L/min (p = 0.007, p < 0.001, and p = 0.005, respectively). The mass median aerodynamic diameter for all trials was less than 5 µm.

CONCLUSION:

: The amount of albuterol delivered with the Vapotherm system using this model was lower than the amount expected for a clinical response for the majority of flow rates and cannula size combinations. Further studies are needed before routine use of aerosolized albuterol through a Vapotherm high-flow system can be recommended.

OBJECTIVES:

: IV corticosteroids are routinely prescribed to treat critically ill children with asthma. However, no specific dosing recommendations have been made for children admitted to the PICU. We aim to determine current asthma corticosteroid dosing preferences in PICUs within North America.

DESIGN:

: Cross-sectional, self-administered survey.

SETTING:

: North American PICUs.

SUBJECTS:

: Pediatric intensivists working in the United States and Canada.

INTERVENTIONS:

: None.

MEASUREMENTS AND MAIN RESULTS:

: A total of 104 intensivists completed the survey. Of these, 70% worked in the United States, 67% attended in PICUs with at most 20 beds, and 79% had more than 10 years of PICU experience. The majority of asthmatics were admitted to PICUs based on clinical asthma examination/score or because the patient was receiving continuous albuterol. IV methylprednisolone is prescribed by the large majority of intensivists (96%). Of those who prescribe methylprednisolone, 66% use a starting dose of 4mg/kg/d, whereas 31% use a starting dose of 2mg/kg/d, and only 3% use 1mg/kg/d. The large majority of respondents (85%) use "clinical experience" as their rationale for their preferred dosage. In multivariate logistic regression analysis, only knowledge of the National Heart, Lung, and Blood Institute guidelines was an independent predictor of prescribing an initial corticosteroid dose of 4mg/kg/d (odds ratio, 3.69 [95% CI, 1.26-10.80]; p = 0.017). Country of practice, years of experience, and PICU size were not associated with corticosteroid dosing preference.

CONCLUSIONS::

Most intensivists administer methylprednisolone to critically ill asthmatics at doses 2-4 times higher than recommended by the National Heart, Lung, and Blood Institute guidelines for hospitalized asthmatic children. The rationale for these decisions is likely multifactorial, but in the absence of evidence-based data, most of them cite clinical experience as their deciding factor. Future research is needed to determine the most appropriate corticosteroid dosage in this critically ill patient population.

To our knowledge, no data exist regarding the effect of levalbuterol and racemic albuterol on heart rate in pediatric cardiology patients.To compare heart rate change in pediatric cardiology patients receiving levalbuterol and/or racemic albuterol. The secondary objective was to identify characteristics associated with heart rate changes observed with these drugs.A review of electronic medical records at a pediatric academic hospital was conducted to determine the equivalence of heart rate change in patients receiving levalbuterol or racemic albuterol. Patients receiving at least 3 doses of levalbuterol and/or racemic albuterol during the study period were included if they were younger than 18 years and had a diagnosis of congenital heart disease (CHD), cardiomyopathy, or supraventricular tachycardia. Patients were excluded if they received a β-blocker or continuous racemic albuterol or did not have documented pre- and postdose heart rates.One hundred ninety-two patients were included. One hundred forty-two received racemic albuterol, 40 received levalbuterol, and 10 received both racemic albuterol and levalbuterol. The mean increase in heart rate for patients receiving racemic albuterol and levalbuterol was 6.8 beats/min and 6.2 beats/min, respectively (p = 0.01). In patients with CHD, the racemic albuterol group experienced a mean heart rate increase of 6.6 beats/min compared to 6.3 beats/min in the levalbuterol group (p = 0.01). Equivalence was also determined in patients without surgical intervention and patients receiving concomitant cardiac and respiratory medications. Equivalence was not established in other analyzed subgroups secondary to insufficient sample sizes.Racemic albuterol and levalbuterol were associated with increased heart rate in pediatric cardiology patients. This increase was found to be equivalent.

The aim of this study was to evaluate and modify commercial dry powder inhalers (DPIs) for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. The optimized device and formulation combination was then tested in a realistic in vitro mouth-throat - tracheobronchial (MT-TB) model. An optimized EEG submicrometer powder formulation, consisting of albuterol sulfate (drug), mannitol (hygroscopic excipient), l-leucine (dispersion enhancer) and poloxamer 188 (surfactant) in a ratio of 30:48:20:2 was prepared using a Büchi Nano spray dryer. The aerosolization performance of the EEG formulation was evaluated with five conventional DPIs: Aerolizer, Novolizer, HandiHaler, Exubera and Spiros. To improve powder dispersion, the HandiHaler was modified with novel mouth piece (MP) designs. The aerosol performance of each device was assessed using a next generation impactor (NGI) at airflow rates generating a pressure drop of 4kPa across the DPI. In silico and in vitro deposition and hygroscopic growth of formulations was studied using a MT-TB airway geometry model. Both HandiHaler and Aerolizer produced high emitted doses (EDs) together with a significant submicrometer aerosol fraction. A modified HandiHaler with a MP including a three-dimensional (3D) array of rods (HH-3D) produced a submicrometer particle fraction of 38.8% with a conventional fine particle fraction (%<5μm) of 97.3%. The mass median diameter (MMD) of the aerosol was reduced below 1μm using this HH-3D DPI. The aerosol generated from the modified HandiHaler increased to micrometer size (2.8μm) suitable for pulmonary deposition, when exposed to simulated respiratory conditions, with negligible mouth-throat (MT) deposition (2.6%).

Rationale Unblinded studies have shown improvements in airway hyper-responsiveness (AHR) with chronic nadolol in steroid naïve asthmatics. Objective To assess the effects of chronic non-selective beta-blockade as add on to inhaled corticosteroids (ICS) in asthmatics. Methods A double-blind randomised placebo controlled crossover trial of propranolol in mild-to-moderate asthmatics receiving ICS was performed. Participants underwent a six to eight week dose titration of propranolol or placebo as tolerated to a maximum of 80mg per day. Tiotropium was given for the first four to six weeks of each treatment period. Measurements Primary outcome was methacholine challenge. Secondary outcomes included histamine challenge, pulmonary function, mini-asthma quality of life questionnaire (mini-AQLQ) and asthma control questionnaire (ACQ). Main Results 18 patients completed: mean (SEM); age 36 (4), FEV1% 93 (2), ICS ug/day 440 (66). No significant difference was observed in methacholine or histamine challenge following exposure to propranolol versus placebo. For methacholine challenge the doubling dilution difference (DDD) was 0·04 (95%CI -0·56 - 0·63), p=0·89. Albuterol recovery at 20mins post histamine challenge was partially attenuated by propranolol vs placebo, FEV1% mean difference: 5.28 (95%CI 2.54-8.01), p=0.001. Post chronic beta-blockade there was a small worsening in FEV1 % predicted of 2·4% (95%CI -0·1 - 4·8), p=0·055. No difference was found for ACQ or mini-AQLQ. Conclusions This is the first placebo controlled study to assess the effects of chronic non-selective beta-blockade in asthma, showing no significant effect of propranolol compared to placebo on either methacholine or histamine AHR and no change in ACQ or AQLQ. Clinical trial registration information available at www.clinicaltrials.gov, i.d. NCT01074853.