Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Metered dose inhalers for bronchodilator delivery in intubated, mechanically ventilated patients. Metered-dose inhaler versus nebulized albuterol in mechanically ventilated patients. Comparative efficacy of jet nebulizer and metered dose inhaler with spacer device in the treatment of acute asthma. Aerosolized metaproterenol in the treatment of asthmatics with severe airflow obstruction. Comparison of two delivery methods. Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with InspirEase in hospitalized asthmatic patients. Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. Comparison of drug delivery from conventional versus "Venturi" nebulizers.
Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction. We determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution nebulized with an updraft inhaler, were compared in a single blind, randomized crossover design. Pulmonary function was evaluated using an interrupter technique. Changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired measurements were made before and 30 minutes after drug delivery. The MDI and NEB resulted in similar improvements in iso-recoil flow (mean increase for both groups = 0.1 L/s). Treatment sequence, severity of obstruction, and bronchodilator responsiveness had no effect on relative efficacy. Albuterol caused a small but significant increase in heart rate that was similar following both delivery methods. We conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients. In nonintubated patients, beta 2-agonist bronchodilators are equally effective when delivered by metered-dose inhalers (MDI) or nebulizers (NEB). The delivery of these drugs by MDI to intubated, mechanically ventilated patients has become a widespread practice. To compare the efficacy of the two delivery systems and establish optimal dosing, we prospectively randomized 10 mechanically ventilated patients, with increased airways resistance, to receive albuterol by either MDI or nebulizer in incrementally higher doses. After a 4-hr washout, patients were crossed-over to receive the drug by the alternative route of administration. Albuterol delivered by NEB to a total dose of 2.5 mg reduced the inspiratory flow-resistive pressure (peak-pause airway pressures) from 21.5 +/- 5.7 to 17.6 +/- 5.4 cm H2O (p < 0.01). Nebulized albuterol at cumulative doses of 7.5 mg led to further reductions in 8 of 10 patients (p < 0.1), but led to toxic side effects in 4 of them; in the remaining 6 patients toxicity occurred at a cumulative dose of 15.0 mg. By contrast, albuterol in cumulative doses reaching 100 puffs (9 mg) from an MDI administered into an endotracheal tube adapter did not significantly reduce resistive pressures, and produced no toxicity. We conclude that nebulized albuterol provides objective physiologic improvement, while albuterol administered by MDI through an endotracheal tube adapter has no effect in mechanically ventilated patients with airflow obstruction. Nebulizer treatments can and should be titrated to higher-than-conventional doses, using toxic side-effects and physiologic response to guide therapy. To compare the relative efficacy of jet nebulizer and metered dose inhaler (MDI) with spacer for the administration of aerosolized salbutamol in an acute exacerbation of bronchial asthma.
                Randomized prospective study.
                Emergency Room.
                In 60 subjects with acute asthma aged between 1 to 12 years, clinical and laboratory assessment of severity at recruitment included heart rate, respiratory rate, pulsus paradoxus, arterial blood gas analysis (all cases) and peak expiratory flow rate (wherever possible). The subjects were randomized into two equal groups to receive aerosolized salbutamol either via nebulizer (Group I) or MDI-spacer (Group II) as per the Consensus Guidelines. The response to therapy was sequentially assessed after 20, 40 and 60 minutes of institution of therapy.
                A significantly (p < 0.02) greater number of subjects in Group II presented with severe dyspnea and intercostal muscle retraction (subjective assessment). However, the objectively evaluable outcome parameters were comparable (p > 0.05) in both groups at presentation. All the outcome measures showed a significant (p < 0.05) improvement with time in both the groups. The recovery parameters were comparable (p > 0.05) at different time periods in the two groups.
                MDI-spacer is as effective as a nebulizer for the aerosolized administration of salbutamol in an acute exacerbation of asthma in children. However, for developing countries, distinct advantages (economic and power requirement) argue strongly for utilization of MDI-spacer in preference to nebulizer. The bronchodilator response to metaproterenol delivered by metered-dose inhaler (MDI) with a spacer device (Aerochamber [A]) and by jet nebulizer was studied in 44 asthmatic patients who presented to the emergency department with acute severe (FEV1 less than 50 percent predicted) airflow obstruction. The delivery method was randomized, double-blinded and placebo controlled. The A group received one puff of metaproterenol every five minutes for a total of three puffs (1.95 mg). The jet nebulizer group received 15 mg of metaproterenol by continuous nebulization over ten minutes. Only about 2.75 mg of the original 15 mg delivered by jet nebulizer was calculated to be available for inhalation due to the inefficiencies of the delivery system. The mean percentage of improvement in FVC and FEV1 in the A group was 33.5 and 49.0 percent, respectively. The mean percentage of improvement in FVC and FEV1 in the jet nebulizer group was 22.8 and 33.0 percent, respectively. There was no significant difference in the mean percentage of improvement values between the two groups. We were unable to demonstrate a difference in bronchodilator response to metaproterenol delivered by MDI-A and jet nebulizer in emergency department asthmatics with acute severe airflow obstruction. The present study was undertaken to determine if beta-agonists delivered by nebulizer provide better clinical responses than MDI therapy in status asthmaticus. We divided 28 hospitalized asthmatic patients into three groups. Group 1 received albuterol by MDI with InspirEase. Group 2 received nebulized albuterol. Group 3 received nebulized metaproterenol. Both nebulizer regimens resulted in significant improvements in both FVC and FEV1 by 30 min after initial hospital beta-agonist treatment. No significant improvement was noted in initial spirometry in the MDI with InspirEase group. In spite of the superiority of nebulizer therapy in the initial phase of hospitalization, the daily rates of spirometric improvement and duration of hospitalization were not significantly different among the three groups. Our results indicate that nebulizer therapy provides superior spirometric improvement in the initial phase of status asthmaticus. However, both MDI and nebulizer regimens provided similar rates of spirometric improvement and duration of hospitalization. A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments. The aim of this study was to compare the response to inhaled albuterol after administration by nebulizer with the response after administration by a metered-dose inhaler and spacer device (MDI-spacer) to children with acute asthma. In a double-blind fashion, 33 children (6 to 14 years of age) with forced expiratory volume in 1 second (FEV1) between 20% and 70% of predicted values, and who were seen in the emergency department with acute asthma, were studied. They were treated with aerosolized albuterol or placebo by MDI-spacer, followed immediately by albuterol or placebo administered by nebulizer with oxygen. The dose ratio for albuterol by MDI-spacer versus nebulizer was 1:5. Outcome measures included a clinical score, respiratory rate, arterial oxygen saturation, and FEV1, measured before and 10, 20, and 40 minutes after treatment. With the exception of heart rate (which increased in the nebulizer group and decreased in the MDI-spacer group (p < 0.05), no difference in the rate of improvement of clinical score, respiratory rate, arterial oxygen saturation, or FEV1 was noted during the 40-minute study period between children who received albuterol by nebulizer and those who received it by MDI-spacer. We conclude that spacers and nebulizers are equally effective means of delivering beta 2-agonists to children with acute asthma. Attempts to improve drug delivery from conventional jet nebulizers have included the use of storage systems to reduce drug wastage during exhalation. Venturi nebulizers enhance drug delivery during inhalation, reducing treatment times and drug wastage. This study investigated the effect of age on inhaled dose from a conventional jet nebulizer (Acorn) used both with and without a storage chamber (Mizer), compared to two Venturi nebulizers (Ventstream and Pari LC). Filters were attached to the four nebulizer systems, containing salbutamol, and 18 children with cystic fibrosis (3-16 yrs) inhaled through these devices. The quantity of drug collected on the filter was assessed using ultraviolet spectrophotometry. The particle size distribution of the aerosol from each nebulizer system was measured using laser diffraction. Inspiratory filter deposition using the Acorn was lower than the Acorn with Mizer, and both Venturi nebulizers. Filter deposition using the Acorn with Mizer was lower than the Pari LC. No trend with age, height or weight was noted using any nebulizer. Aerosol particle size using the Ventstream was lower than the other nebulizer systems. Drug output from both Venturi nebulizers was more efficient than from the jet nebulizer, used with and without the storage chamber, during inhalation by children with cystic fibrosis. The inhaled dose did not change with the patient's age or size using both types of nebulizer.
Existing randomized controlled trials, including randomized cross-over trials where the order of the intervention was randomized, comparing nebulizer and MDI for aerosol bronchodilation in mechanically ventilated adult patients do not provide sufficient evidence to support either delivery method at this time.