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Three Part Question

Does intravenous salbutamol [intervention] result in quicker relief of the respiratory distress [outcome] than intravenous aminophylline, for a child with acute severe asthma [patient group]?

Clinical Scenario

You are the paediatric registrar in a district general hospital. An 8 year old boy, who is known to have asthma, presents to the paediatric assessment unit acutely with severe exacerbation of asthma. He has received back to back nebulisers of salbutamol and ipratropium bromide with no improvement in his condition. You are inclined to give an intravenous bolus of salbutamol to the child. However, the paediatric nurse informs you that they are familiar only with the use of intravenous aminophylline. You perform a literature search to seek evidence for the comparative efficacy of intravenous salbutamol vs. aminophylline in the management of this child.

Search Strategy

Cochrane Library (January 2010 issue),
MEDLINE (NHS Evidence interface 1950-22/4/2010) and EMBASE (NHS Evidence interface 1980-22/4/2010)
(salbutamol or albuterol) and aminophylline and (intravenous or IV) and severe asthma and child*,(exp ALBUTEROL/ or salbutamol or albuterol) and (exp AMINOPHYLLINE/ or aminophylline) and (intravenous or IV) and (exp ASTHMA/ or asthma) and severe, limited to Child) finding 22 and 19 results respectively.

Search Outcome

We found 2 randomised controlled trials comparing the efficacy of salbutamol and aminophylline in acute asthma in children.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
G. Hambleton 1979 UK	18 children (2-7yrs)	Randomised double blind controlled trial (level 2b)	Improvement in the clinical signs and vital parameters monitored at 1,2,6,12,18, 24 hours	No significant difference	1.Doses of aminophylline used were inadequate 2.Salbutamol bolus and infusion used
G Roberts, D Newsom, K Gomez, A Raffles, S Saglani, J Begent, P Lachman, K Sloper, R Buchdahl 2003 UK	44 children (1-16yr)	Randomised double blind controlled trial (level 2b)	Asthma severity score assessed at 1,2,6,12,24 hours	No significant difference at 2hours	Single bolus of salbutamol used Significant increase in the hospital stay and increased oxygen therapy in the salbutamol group

Comment(s)

Intravenous salbutamol has been recommended in the management of acute moderate to severe asthma in adults not responding to inhaled bronchodilators (3). A recent Cochrane review compared aminophylline with placebo in children with severe acute asthma receiving treatment with inhaled bronchodilators and systemic glucocorticoids (4). It showed that aminophylline improves lung function, reduces clinical severity, and reduces the need for ventilation. Intravenous aminophylline and salbutamol have only been compared in severe acute childhood asthma in two studies (1,2). The limitations of the first study were the use of inadequate intravenous dosages, no concurrent nebulised therapy, and small sample size. The second study was more rigorous in their methodology and compared a single bolus of salbutamol with aminophylline infusion in children who have not responded despite nebulised bronchodilators. They concluded that there was no significant difference in the effectiveness of intravenous aminophylline and salbutamol in the first 2 hours of treatment. They also noted that the children who received aminophylline required less duration of oxygen therapy and stay in the hospital. Again this study has a small sample size. The treatment efficacy was assessed using the asthma severity score, which although a validated tool, is unlikely to demonstrate a significant difference between the two treatments within 2 hours. This could have been modified by increasing the sample size or using other outcomes as well for efficacy i.e. the need for mechanical ventilation.

Clinical Bottom Line

There are not many good sized randomised controlled trials comparing aminophylline and intravenous bronchodilators in asthma in the the paediatric age group. Further clinical studies are required to determine whether multiple intravenous boluses of salbutamol/salbutamol infusion are as effective as an aminophylline infusion in the short term outcome of children with acute severe asthma. Till then every paediatric unit must have a protocol for the management of acute severe asthma which everyone must be familiar with.

References

1. G. Hambleton Comparison of IV salbutamol with IV aminophylline in the treatment of severe, acute asthma in childhood. Archives of Disease in Childhood 1979, 54, 391-402
2. G Roberts, D Newsom, K Gomez, A Raffles, S Saglani, J Begent, P Lachman, K Sloper, R Buchdahl, A Habel Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial Thorax 2003;58:306–310