The Effectiveness of IV β-Agonists in Treating Patients with Acute Asthma in the Emergency Department: A Meta-analysis

doi:10.1378/chest.122.4.1200

Chest

Volume 122, Issue 4, October 2002, Pages 1200-1207

https://doi.org/10.1378/chest.122.4.1200 Get rights and content

Objectives

To determine the benefit of IV β₂-agonists for severe acute asthma treated in the emergency department (ED).

Methods

Randomized controlled trials were identified using EMBASE, MEDLINE, and CINAHL; the Cochrane Airways Review Group database; hand searching; bibliographies; pharmaceutical companies; and author contact. Studies where IV β₂-agonists were compared to placebo and/or existing standards of care were considered. Where appropriate, trials were combined using odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CIs).

Results

From 746 identified references, 55 potentially relevant articles were identified and 15 articles were included. All trials were performed outside North America and were published prior to 1997. Three main treatment strategies were reviewed: strategy 1 (three articles), IV β₂-agonists with inhaled β₂-agonists vs inhaled β₂-agonists; strategy 2 (six articles), IV β₂-agonists alone vs inhaled β₂-agonists; and strategy 3 (six articles), IV β₂-agonists vs IV methylxanthines. Compared to all treatments, IV β₂-agonist use did not lead to clinical or statistical significant differences in vital signs, pulmonary functions, laboratory measures, adverse effects, or clinical success. Although statistically nonsignificant, seven methodologically strong studies demonstrated that peak expiratory flows and heart rates were unchanged following β₂-agonist use compared to all other treatments at 60 min (8.3 L/min [95% CI, 17.6 to 34.2] and 3.65 beats/min [95% CI, 2.9 to 10.2], respectively), with an increased risk of adverse effects (OR, 1.98; 95% CI, 0.5 to 8.2).

Conclusions

Evidence is lacking to support the use of IV β₂-agonists in ED patients with severe acute asthma. Moreover, the clinical benefit appears questionable, while the potential clinical risks are obvious. The only recommendations for IV β-₂agonist use should be in those patients in whom inhaled therapy is not feasible, or in the context of a controlled clinical trial comparing IV β₂-agonists with standard care vs standard care alone.

Section snippets

Inclusion Criteria

To be eligible for inclusion in this review, a study had to meet all of the following criteria: (1) design, randomized controlled trials (RCTs) or quasi RCTs (allocation on days of the week, or some other method); (2) population, studies recruiting adult or pediatric patients with severe acute asthma from the ED (or its equivalent); (3) interventions, administration of IV (selective or nonselective) β-agonists vs the administration of placebo, other IV bronchodilators (ie, methylxanthines), or

Systematic Review

The Airways Review Group database search revealed 976 references that represented 740 original publications (76%): 258 articles (35%) in EMBASE, 250 articles (34%) in MEDLINE, 2 articles (0.3%) from CINAHL, 224 articles (30%) from both MEDLINE and EMBASE, and 6 articles (0.7%) cited in all three. An independent review of the abstracts and titles of these publications identified 31 potentially relevant studies. The agreement for relevance was high (κ = 0.83). Twenty-four additional references

Pulmonary Function

Table 2 demonstrates that across the 6-h observation in the seven articles reporting PEFR, no statistical differences in PEFR were identified between those patients who received IV β₂-agonists vs inhaled β₂-agonists or IV methylxanthines. Moreover, differences between the summary outcome measures in each stratum were of questionable clinical significance with pooled estimates of treatment effect ranging from a 0.4 to 19.4 L/min. Over the course of 6 h, there were no statistically or clinically

Discussion

The literature has been conflicting regarding the use of IV β₂-agonists in patients with acute asthma, and this systematic review is the first to examine the available evidence of the effect of treating severe acute asthmatics with IV β₂-agonists. The subsequent meta-analysis included 15 randomized trials over 25 years that included 584 adults and children across nine countries. IV β₂-agonists administered either by bolus or infusion compared to inhaled β₂-agonists or IV methylxanthines did not

Conclusion

Despite the methodologic limitations, the results of this work clarify the use of IV β₂-agonists in the treatment of severe acute asthma. The use of IV β₂-agonists compared to inhaled β₂-agonists or IV methylxanthines did not lead to any significant differences in pulmonary functions, laboratory measures of ventilation and oxygenation, or clinical failure/success. Although statistically nonsignificant, IV β₂-agonists produced slightly more autonomic side effects and tachycardia than do

ACKNOWLEDGMENT

The authors thank Stephen Milan, Anna Bara, and Jane Dennis of the Cochrane Airways Review Group. The editorial assistance of Professor Paul Jones (Cochrane Airways Review Group Coordinating Editor) and the abstraction of data by Carol Spooner were greatly appreciated.

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Epinephrine, given subcutaneously or IM, should be considered an option for severe exacerbations, particularly as initial treatment of patients with significant airway obstruction when delivery of inhaled medications to the lower airways may be limited. Terbutaline may be administered subcutaneously and is also commonly administered as a continuous IV infusion, although pediatric studies evaluating such protocols are limited.48,49 Noninvasive ventilatory support bilevel positive airway pressure may benefit patients tiring from increased work of breathing and with impending respiratory failure.
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Lors des exacerbations d’asthme, une mauvaise évaluation de la sévérité, un traitement initial inadéquat et un retard au recours à des structures d’urgence sont des facteurs de surmortalité. Cette revue est centrée sur les formes graves.
Les conséquences de l’obstruction bronchique sur la mécanique ventilatoire et son retentissement cardiocirculatoire expliquent les critères de sévérité des exacerbations. L’histoire ancienne et récente, la sévérité initiale et la réponse au traitement conditionnent l’orientation : passage aux urgences, admission en pneumologie ou en réanimation. Le traitement immédiat comporte correction de l’hypoxémie, nébulisations répétées de bronchodilatateurs et administration précoce de corticoïdes systémiques. La ventilation mécanique est indiquée en cas d’asphyxie ou d’épuisement. Il s’agit d’une ventilation de sécurité aboutissant à une hypercapnie permissive pour éviter tout barotraumatisme. Les traitements adjuvants, dérivés halogénés ou héliox sont discutés.
Le nombre de décès par asthme a diminué ces dernières années en France (< 1000 par an) et la majorité survient au domicile ou durant le transport. En dehors des cas d’asphyxie, ils seraient évitables si on considérait que toute exacerbation est potentiellement fatale. Cette notion devrait être renforcée dans les programmes d’éducation des patients et de formation des médecins.
All patients with asthma are at risk of exacerbations. Mortality is often associated with failure to identify patients at risk and/or to appreciate the severity of acute episode, resulting in inadequate initial treatment, delay in referring to emergency care and inappropriate hospitalization rates, including delayed transfer to intensive care units. This review focuses on the management of acute severe and near fatal asthma.
Lung mechanics and cardiopulmonary interactions associated with airflow obstruction explain the physical presentation and severity criteria for exacerbations. The past and recent medical history, the initial evaluation of severity and the assessment of response to treatment direct the in-hospital management: emergency department visit, transfer to ward or intensive care unit. In any cases, the goals of therapy are summarized as oxygenation, repetitive inhalations of bronchodilators and early administration of systemic corticosteroids. Mechanical ventilation is required in a few patients with near fatal attacks resulting in asphyxia or progressive exhaustion despite maximal therapy. Controlled hypoventilation with permissive hypercapnia is the best strategy to avoid barotrauma. The role of adjunctive therapies, mainly halogenated agents and heliox, is discussed.
During the last decade, asthma related mortality has decreased in France (< 1000/year). The majority of deaths occur at home or during transport to the hospital but some deaths occur suddenly. Most deaths could be preventable if one adopts the approach that every exacerbation is potentially fatal. This practice should be more vigorously included in patient and general practitioner educational programs.
Beyond the guidelines: Fatal and near-fatal asthma
2012, Paediatric Respiratory Reviews
Citation Excerpt :
These are often given in large doses by aerosol, systemically, or occasionally by both routes simultaneously. Clinical trials have shown that there is no advantage to the systemic administration (oral, intravenous, or intramuscular) administration of beta agonist bronchodilators as compared to aerosol administration42 nor is there any advantage to combining systemic with aerosol administration43. Although intravenous or intramuscular beta agonists are included in asthma care guidelines as add on therapy for severe asthma that is “unresponsive” to aerosol beta agonist, randomized controlled trials show a modest clinical benefit at best, with the possibility of side effects43,44
While asthma is extremely common, fatal and near fatal asthma is rare and often preventable if there is early recognition of symptom progression and appropriate intervention. In the past decade, asthma mortality has progressively declined in association with the widespread use of inhaled corticosteroids and asthma care plans. Management of life threatening asthma requires patient education to ensure the proper use of medications and to enable the patient to recognize when additional therapy for poorly controlled asthma is required. There is some evidence that suggests that the overly aggressive use of asthma medications when treating a severe exacerbation may contribute to morbidity. Because of the risks of air trapping and barotrauma associated with partial airway obstruction, it is best to avoid mechanical ventilation if possible but when this is used, low tidal volumes, longer exhalation times, and permissive hypercarbia can minimize these risks. There is the promise that a better understanding of asthma immunology and severe asthma “phenotypes” will lead to better prevention and therapy.
Management of acute asthma
2012, Revue des Maladies Respiratoires
Lors des exacerbations d’asthme, une mauvaise évaluation de la sévérité, un traitement initial inadéquat et un retard au recours à des structures d’urgence sont des facteurs de surmortalité. Cette revue est centrée sur les formes graves.
Les conséquences de l’obstruction bronchique sur la mécanique ventilatoire et son retentissement cardiocirculatoire expliquent les critères de sévérité des exacerbations. L’histoire ancienne et récente, la sévérité initiale et la réponse au traitement conditionnent l’orientation : passage aux urgences, admission en pneumologie ou en réanimation. Le traitement immédiat comporte correction de l’hypoxémie, nébulisations répétées de bronchodilatateurs et administration précoce de corticoïdes systémiques. La ventilation mécanique est indiquée en cas d’asphyxie ou d’épuisement. Il s’agit d’une ventilation de sécurité aboutissant à une hypercapnie permissive pour éviter tout barotraumatisme. Les traitements adjuvants, dérivés halogénés ou héliox sont discutés.
Le nombre de décès par asthme a diminué ces dernières années en France (< 1000 par an) et la majorité survient au domicile ou durant le transport. En dehors des cas d’asphyxie, ils seraient évitables si on considérait que toute exacerbation est potentiellement fatale. Cette notion devrait être renforcée dans les programmes d’éducation des patients et de formation des médecins.
All patients with asthma are at risk of exacerbations. Mortality is often associated with failure to identify patients at risk and/or to appreciate the severity of acute episode, resulting in inadequate initial treatment, delay in referring to emergency care and inappropriate hospitalization rates, including delayed transfer to intensive care units. This review focuses on the management of acute severe and near fatal asthma.
Lung mechanics and cardiopulmonary interactions associated with airflow obstruction explain the physical presentation and severity criteria for exacerbations. The past and recent medical history, the initial evaluation of severity and the assessment of response to treatment direct the in-hospital management: emergency department visit, transfer to ward or intensive care unit. In any cases, the goals of therapy are summarized as oxygenation, repetitive inhalations of bronchodilators and early administration of systemic corticosteroids. Mechanical ventilation is required in a few patients with near fatal attacks resulting in asphyxia or progressive exhaustion despite maximal therapy. Controlled hypoventilation with permissive hypercapnia is the best strategy to avoid barotrauma. The role of adjunctive therapies, mainly halogenated agents and heliox, is discussed.
During the last decade, asthma related mortality has decreased in France (< 1000/year). The majority of deaths occur at home or during transport to the hospital but some deaths occur suddenly. Most deaths could be preventable if one adopts the approach that every exacerbation is potentially fatal. This practice should be more vigorously included in patient and general practitioner educational programs.
An under-recognized complication of treatment of acute severe asthma
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View all citing articles on Scopus

Presented at the American College of Emergency Physicians Annual Meeting, Las Vegas, NV, October 1999, and the Canadian Association of Emergency Physicians Annual Meeting, Quebec City, PQ, Canada, October, 1999.

These results have been electronically published by the Airways Review Group in the Cochrane Collaboration (Cochrane Database of Systematic Reviews. The Cochrane Library, Issue 4, 2001. Oxford, UK: Update Software). Dr. Travers received a grant from the Canadian Association of Emergency Physicians to complete this work. Dr. Rowe is supported by a salary award from the Canadian Institute of Health Research as the Chair in Emergency Airway Diseases (Ottawa, ON). Dr. Camargo is supported by grant HL-03533 from the National Institutes of Health (Bethesda, MD).

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Chest

Clinical InvestigationsThe Effectiveness of IV β-Agonists in Treating Patients with Acute Asthma in the Emergency Department: A Meta-analysis

Objectives

Methods

Results

Conclusions

Section snippets

Inclusion Criteria

Systematic Review

Pulmonary Function

Discussion

Conclusion

ACKNOWLEDGMENT

Lancet

Control Clin Trials

Treatment of acute asthma

Lancet

Guidelines for the emergency management of asthma in adults

Can Med Assoc J

Canadian Asthma Consensus Conference: summary of recommendations

Can Respir J

Cochrane collaboration handbook. The Cochrane Library. Issue 4, 2001

Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials

JAMA

Comparison of salbutamol given intravenously and by intermittent positive-pressure breathing in life-threatening asthma

BMJ

A controlled trial on intravenous salbutamol and aminophylline in acute asthma

Med J Aust

Intravenous β-agonist in severe acute asthma

BMJ

Intravenous vs nebulized terbutaline in patients with acute severe asthma: a double-blind randomized study

Ann Allergy

Clinical Investigations
The Effectiveness of IV β-Agonists in Treating Patients with Acute Asthma in the Emergency Department: A Meta-analysis