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Three Part Question

In [adults presenting with an acute exacerbation of asthma] does [adding IV aminophylline to standard therapy] result in [improvement in airflow or other physiological parameters] OR [a reduction in mortality or morbidity or hospitalisation]?

Clinical Scenario

A 30 year old known asthmatic presents with an acute severe attack of asthma. Despite administering continuous nebulised beta-agonists and intravenous corticosteroids, he fails to improve. You wonder whether adding an intravenous bolus of aminophylline followed by an infusion to his therapy would be beneficial.

Search Strategy

The Cochrane Library 2007 Issue 1, searched on 26/03/2007.
MEDLINE 1999 to March Week 3 2007 using the OVID interface.
COCHRANE: asthma AND aminophylline.
MEDLINE: [exp asthma/ OR asthma$.mp OR exp status asthmaticus/ OR status asthmaticus$.mp] AND [exp aminophylline/ OR aminophylline$.mp OR exp. xanthines/ OR methyl xanthine$.mp OR exp. theophylline or theophylline$.mp] AND [highly sensitive filter for randomised controlled trials] LIMIT to Human and English

Search Outcome

One systematic review was identified by the Cochrane Library search. The MEDLINE search identified 292 papers of which 290 were irrelevant or of insufficient quality, leaving 2 selected papers. The two identified papers were the Cochrane review and the other was a short commentary on the Cochrane review with no new additional evidence.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Parameswaran K, Belda J and Rowe BH 2000	739 adult patients (>18 years of age) from 17 randomised controlled trials, presenting with acute asthma in an acute care setting. 386 recieved standard care (oxygen and beta-agonists (nebulised or inhaled) +/- corticosteroids) 353 recieved standard care + IV aminophylline	Systematic Review (Level 1a)	Change in PEFR at 05, 1, 12 and 24 hours after administration	No significant difference at any time.	Variety of outcome measures used between studies - both PEFR and FEV1, expressed both as % of predicted and absolute values. Baseline difference in PEFR and FEV1 between groups (lower values in pooled treatment group). Variety of beta-agonists used betwen trials and administered through a variety of routes; no subgroup analysis looking at the effect of this. Only three studies had samples sizes greater than 30 subjects.
			Change in FEV1 at 0.5, 1, 12 and 24 hours after administration	No significant difference at any time.
			Hospitalization	No significant difference.
			Adverse Effects	Significantly higher incidence of palpitations and/or arrhythmias (OR 3.02 95%CI 1.2-7.9) and vomiting (OR 4.21 95%CI 2.2-8.1) in aminophylline group. No significant difference in incidence of tremor. Insufficient data to produce results for convulsion or hypokalaemia.

Comment(s)

The use of intravenous aminophylline as a routine agent in the treatment of acute asthmatics has declined in the last few years. In a recent observational paper by Kelly A-M et al (Internal Medicine Journal 2003;33:406-13.) looking at 1340 attendances to the ED with acute asthma only 6% of cases were treated with aminophylline. The Cochrane review failed to show any evidence of benefit especially in severe asthma. The use of intravenous aminophylline was associated with a higher incidence of adverse effects compared to standard care alone. Whether or not aminophylline has a place as an additional therapy following treatment with proven medications such as inhaled B-agonists, systemic corticosteroids and intravenous magnesium remains uncertain.

Clinical Bottom Line

Current evidence does not support the addition of intravenous aminophylline to standard care in adults with acute asthma.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

1. Parameswaran K, Belda J and Rowe BH Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma The Cochrane Database of Systematic Reviews 2000, Issue 4