A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma

doi:10.1016/j.jemermed.2006.05.025

The Journal of Emergency Medicine

Volume 31, Issue 4, November 2006, Pages 371-376

https://doi.org/10.1016/j.jemermed.2006.05.025 Get rights and content

Abstract—

Multiple studies have examined adding nebulized ipratropium bromide to intermittent albuterol for the treatment of acute asthma. Although continuous nebulized treatments in themselves offer benefits; few data exist regarding the efficacy of adding ipratropium bromide to a continuous nebulized system. To compare continuous nebulized albuterol alone (A) vs. albuterol and ipratropium bromide (AI) in adult Emergency Department (ED) patients with acute asthma, a prospective, randomized, double-blind, controlled clinical trial was conducted on a convenience sample of patients (IRB approved). The setting was an urban ED. Consenting patients > 18 years of age with peak expiratory flow rates (PEFR) < 70% predicted, between October 15 and December 28, 1999, were randomized to albuterol (7.5 mg/h) + ipratropium bromide (1.0 mg/h), or albuterol alone via continuous nebulization using the Hope Nebulizer (B&B Technologies Inc., Orangevale, CA) for 2 h. Main outcome measures were changed in mean improvement at 60 and 120 min PEFR compared to baseline (time 0). Secondary measures were admission rates. Data were analyzed using appropriate parametric and non-parametric tests (p < 0.05 statistically significant). Sixty-two patients (30 women) completed enrollment: 32 in (AI) and (30) in (A). Four (A) and 2 (AI) patients are without 120 min data: 3 (A) and 1 (AI) were discharged after 60 min, whereas one each (A) and (AI) worsened and were admitted before 120 min. There were no statistically significant differences between treatment groups in age, sex, predicted or initial PEFR. Thirteen (19.4%) patients were admitted. There was no statistically significant difference in improvement of mean PEFR at 60 min or 120 min compared to baseline, between groups, using repeated measures analysis of variance. Mean improvement in PEFR at 60 min compared to baseline (time 0): (A) = 93.2 L/min (95% confidence interval [CI] 64.5–121.8), (AI) = 86.6 L/min (95% CI 58.9–114.3); mean improvement in PEFR at 120 min compared to baseline (time 0) (A) = 116.5 L/min (95% CI 84.5–148.5), (AI) = 126.4 L/min (95% CI 95.4–157.4). There was no statistically significant difference in admission rates between groups: 5/30 (A) and 8/32 (AI) (p = 0.62). There were no significant differences in mean improvement of PEFR at either 60 or 120 min between ED patients with acute asthma receiving continuous albuterol alone vs. those receiving albuterol in combination with ipratropium bromide.

Introduction

Asthma is a common presenting complaint of Emergency Department (ED) patients, accounting for 1.5 million ED visits, 450,000 admissions, and 5000 deaths each year (1, 2).

The standard of care in the treatment of acute asthma has evolved to the use of inhaled B2-adrenergic agonists, and with moderate or severe cases, the early use of oral corticosteroids (3, 4, 5). Furthermore, the interval between nebulized B2-agonist treatments has decreased progressively from every 4 h to the current practice of treatment of every 20–30 min. Although considerable data have been published regarding the safety and efficacy of using nebulized parasympatholytics (atrovent/ipratropium bromide) in conjunction with B2-agonists in the treatment of acute asthma, other studies have failed to confirm its benefit (4, 5, 6, 7, 8, 9, 10, 11, 12).

Other treatment options now also include the use of continuous nebulized B2-agonists, which over a period of 2 h have been shown to be as effective for the treatment of acute asthma (and probably more effective in severe cases) when compared with intermittent nebulized B2-agonists (13). Further benefits of continuous nebulization B2-agonists include the amount of time and effort saved in administering treatments, which may lead to more timely treatment, an important consideration in busy EDs (13). Studies have shown there are no adverse physiologic side effects to the use of continuous B2-agonist treatments in standard doses (14, 15).

Our study was designed to examine the effects of adding ipratropium bromide to continuous albuterol with regards to peak expiratory flow rate (PEFR) in ED patients with acute asthma. We hypothesized that the use of an albuterol-ipratropium solution would increase PEFR by 75 L/min compared to albuterol alone.

Section snippets

Study Design

This study was a randomized double blind clinical trial on a convenience sample of patients between October 15 and December 28, 1999. The hospital’s institutional review board (IRB) approved the study. Written informed consent was obtained from all participants.

Study Setting and Population

The setting was the adult side of an inner-city hospital ED (Newark Beth Israel), with an Emergency Medicine resident program and a combined adult and pediatric annual volume of 75,000 patients (adult visits 55,000/year). Eighty-five to

Results

Review of our ED electronic tracking system showed there were 375 patients during the study period who had a diagnosis of acute asthma. Of these, 166 (44.2%) would have been eligible for study enrollment. Five potential study patients were triaged to fast-track, a separate ED area not included for study enrollment. Of the remaining 161, 69 were approached. Three refused and sixty-six were rapid consented, examined, completed study demographics, and prepared for study treatment. From this group,

Discussion

One other study, by Weber et al., has compared continuous nebulized B2-agonists with continuous nebulized B2-agonists to which ipratropium bromide has been added for the treatment of acute asthma in adults (12).This study of adult patients also failed to show an improvement in PEFR at 60 or 120 min, or a change in admission rates. Weber et al., however, followed patients an additional hour (total of 3 h) and although they reported no statistically significant change in outcomes at hour 3, they

Limitations

Our study was limited by several factors. First, the numbers enrolled were small, thus limiting our ability to detect small but potential clinically significant differences. In addition, 92 patients during the study period were not approached. Although selection bias may have been the cause of this, the lack of a dedicated full-time research coordinator, and the fact that a convenience sample of patients was approached likely accounted for the percent of eligible patients approached and

Conclusions

This was the second trial comparing continuous nebulized albuterol with ipratropium bromide to albuterol alone that failed to show a difference in 2-h PEFR or admission rates in patients with acute asthma presenting to an Emergency Department. Whereas this questions the use of ipraptropium bromide in the ED setting, its low adverse event profile, coupled with a possible delayed effect, suggests further studies should be performed on the possible benefits of this medication.

Acknowledgments—

The authors wish to thank the staff, attendings, residents, and nurses of the Emergency Department at Newark Beth Israel Medical Center Hospital for their help in this study. We also thank B&B Medical Technologies Inc., Orangevale, CA, for donation of the Hope Nebulizers used in this study.

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Original contributionA randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma

Abstract—

Introduction

Section snippets

Study Design

Study Setting and Population

Results

Discussion

Limitations

Conclusions

Acknowledgments—

Ann Emerg Med

Ann Emerg Med

Ann Emerg Med

Chest

Chest

Ann Emerg Med

Chest

Chest

Chest

Original contribution
A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma