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Meta-Analysis
. 2012 Dec 12;12(12):CD002742.
doi: 10.1002/14651858.CD002742.pub2.

Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma

Parameswaran Nair  1 , Stephen J Milan, Brian H Rowe
Affiliations
Meta-Analysis

Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma

Parameswaran Nair et al. Cochrane Database Syst Rev. .

Abstract

Background: Asthma is a chronic condition in which sufferers may have occasional or frequent exacerbations resulting in visits to the emergency department (ED). Aminophylline has been used extensively to treat exacerbations in acute asthma settings; however, it's role is unclear especially with respect to any additional benefit when added to inhaled beta(2)-agonists.

Objectives: To determine the magnitude of effect of the addition of intravenous aminophylline to inhaled beta(2)-agonists in adult patients with acute asthma treated in the ED setting.

Search methods: We identified trials from the Cochrane Airways Group register (derived from MEDLINE, EMBASE, CINAHL standardised searches) and handsearched respiratory journals and meeting abstracts. Two independent review authors screened and obtained potentially relevant articles and handsearched their bibliographic lists for additional articles. In the original version of this review published in 2000 we included searches of the database up to 1999. The 2012 review was updated with a revised search from inception to September 2012.

Selection criteria: Randomised controlled trials comparing intravenous aminophylline versus placebo in adults with acute asthma and treated with inhaled beta(2)-agonists. We included patients who were treated with or without corticosteroids or other bronchodilators provided this was not part of the randomised treatment.

Data collection and analysis: Two review authors independently extracted data and one review author entered data into RevMan, which was checked by a second review author. Results are reported as mean differences (MD) or odds ratios (OR) with 95% confidential intervals (CI).

Main results: Fifteen studies were included in the previous version of the review, and we included two new studies in this update, although we were unable to pool new data. Overall, the quality of the studies was moderate; concealment of allocation was assessed as clearly adequate in only seven (45%) of the trials. There was significant clinical heterogeneity between studies as the doses of aminophylline and other medications and the severity of the acute asthma varied between studies.There was no statistically significant advantage when adding intravenous aminophylline with respect to hospital admissions (OR 0.58; 95% CI 0.30 to 1.12; 6 studies; n = 315). In 2000 it was found that there was no statistically significant effect of aminophylline on airflow outcomes at any time period; the addition of two trials in 2012 has not challenged this conclusion. People treated with aminophylline and beta(2)-agonists had similar peak expiratory flow (PEF) values compared to those treated with beta(2)-agonists alone at 12 h (MD 8.30 L/min; 95% CI -20.69 to 37.29 L/min) or (MD -1.21% predicted; 95% CI -14.21% to 11.78% predicted) and 24 h (MD 22.20 L/min; 95% CI -56.65 to 101.05 L/min). Two subgroup analyses were performed by grouping studies according to mean baseline airflow limitation (11 studies) and the use of any corticosteroids (nine studies). There was no relationship between baseline airflow limitation or the use of corticosteroids on the effect of aminophylline. Aminophylline-treated patients reported more palpitations/arrhythmias (OR 3.02; 95% CI 1.15 to 7.90; 6 studies; n = 249) and vomiting (OR 4.21; 95% CI 2.20 to 8.07; 7 studies; n = 321); however, no significant difference was found in tremor (OR 2.60; 95% CI 0.62 to 11.02; 5 studies; n = 249).

Authors' conclusions: The use of intravenous aminophylline did not result in significant additional bronchodilation compared to standard care with inhaled beta(2)-agonists in patients experiencing an asthma exacerbation in the ED setting, or in a significant reduction in the risk of hospital admission. For every 100 people treated with aminophylline an additional 20 people had vomiting and 15 people arrhythmias or palpitations. No subgroups in which aminophylline might be more effective were identified. Our update in 2012 is consistent with the original conclusions that the risk-benefit balance of intravenous aminophylline is unfavourable.

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Conflict of interest statement

The authors who have been involved in this review have done so without any known conflicts of interest. They are not involved with the primary studies. Moreover, none of the authors are considered paid consultants by any pharmaceutical companies that produce aminophylline agents.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Aminophylline vs. placebo, outcome: 1.2 PEF (L/min).
4
4
Forest plot of comparison: 1 Aminophylline vs. placebo, outcome: 1.3 PEFR (% predicted).
5
5
Forest plot of comparison: 1 Aminophylline vs. placebo, outcome: 1.4 FEV1 (L).
6
6
Forest plot of comparison: 1 Aminophylline vs. placebo, outcome: 1.5 FEV1 (% predicted).
7
7
Forest plot of comparison: 1 Aminophylline vs. placebo, outcome: 1.1 Hospital admissions.
8
8
Arrhythmia/palpitations: in the control group 10 people out of 100 had arrhythmias or palpitations, compared to 25 out of 100 (95% CI 11 to 47) for the IV aminophylline group.
9
9
Vomiting: in the control group nine people out of 100 had vomiting, compared to 29 out of 100 (95% CI 18 to 44) for the IV aminophylline group.
1.1
1.1. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 1 Hospital admissions.
1.2
1.2. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 2 PEF (L/min).
1.3
1.3. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 3 PEF (% predicted).
1.4
1.4. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 4 FEV1 (L).
1.5
1.5. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 5 FEV1 (% predicted).
1.6
1.6. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 6 Tremor.
1.7
1.7. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 7 Vomiting.
1.8
1.8. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 8 Arrythmia/palpitations.
1.9
1.9. Analysis
Comparison 1 Aminophylline vs Placebo, Outcome 9 Convulsions.
2.1
2.1. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 1 PEF (L/min) or PEF (%) if missing at baseline.
2.2
2.2. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 2 PEF (L/min) or PEF (%) if missing at 30 min.
2.3
2.3. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 3 PEF (L/min) or PEF (%) if missing at 60 min.
2.4
2.4. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 4 PEF (L/m) or PEF (%) if missing at 12 h.
2.5
2.5. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 5 PEF (L/min) or PEF (%) if missing at 24 h.
2.6
2.6. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 6 FEV1 (L) or FEV1 (%) if missing at baseline.
2.7
2.7. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 7 FEV1 (L) or FEV1 (%) if missing at 30 min.
2.8
2.8. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 8 FEV1 (L) or FEV1 (%) if missing at 12 h.
2.9
2.9. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 9 FEV1 (L) or FEV1 (%) if missing at 60 min.
2.10
2.10. Analysis
Comparison 2 Aminophylline vs placebo (grouped by baseline severity), Outcome 10 FEV1 (L) or FEV1 (%) if missing at 24 h.
3.1
3.1. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 1 PEF (L/min) or PEF (%) if missing at baseline.
3.2
3.2. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 2 PEF (L/min) or PEF (%) if missing at 30 min.
3.3
3.3. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 3 PEF (L/min) or PEF (%) if missing at 60 min.
3.4
3.4. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 4 PEF (L/min) or PEF (%) if missing at 12 h.
3.5
3.5. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 5 PEF (L/min) or PEF (%) if missing at 24 h.
3.6
3.6. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 6 FEV1 (L) or FEV1 (%) if missing at baseline.
3.7
3.7. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 7 FEV1 (L) or FEV1 (%) if missing at 30 min.
3.8
3.8. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 8 FEV1 (L) or FEV1 (%) if missing at 60 min.
3.9
3.9. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 9 FEV1 (L) or FEV1 (%) if missing at 12 h.
3.10
3.10. Analysis
Comparison 3 Aminophylline vs placebo (grouped by corticosteroid use), Outcome 10 FEV1 (L) or FEV1 (%) if missing at 24 h.
See this image and copyright information in PMC

Update of

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