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Three Part Question

In [children with acute asthma] does [nebulised epinephrine as opposed to nebulised beta-two agonists] [improve respiratory function and decrease hospitalisation].

Clinical Scenario

A child presents with acute asthma. You start standard treatment with salbutamol, ipratropium and steroids. Your medical student points out that nebulised epinephrine is used for children with acute severe bronchiolitis, and wonders why you do not use the same treatment in asthma.

Search Strategy

Ovid Medline(R) 1950 - Feb Week 1 2007
NCBI PubMed
For Medline(R):
1 Asthma/
2 Epinephrine/ad, tu, th [Administration & Dosage, Therapeutic Use, Therapy]
3 1 and 2
4 limit 3 to (humans and english language)
For PubMed:
Epinephrine and Asthma

Search Outcome

276 potential papers from Medline(R) and 48 from PubMed, of which 6 were considered suitable on reviewing the abstracts. When the full text was read, 3 studied adults only while one was in French. 2 papers were suitable for further analysis on reading the full text.
There was also a meta-analysis found (AJEM 2006 Vol 24 217-222), but this analysed only one paper in children. Since this paper is reviewed here, it was not added to the BET.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Plint AC, Osmond MH, Klassen TP October 2000 Canada	All children (1-18 years old) admitted to ED of a childrens hospital in Eastern Ontario between March-May and October-December with an acute asthma attack.	A prospective randomised double-blind study of children treated with oral steroids and either nebulised salbutamol or nebulised racaemic epinephrine for acute asthma.	Pulmonary index scores (similar to FEV1).	No significant difference	Excluded children with severe asthma, those with respiritoy distress and those needing intensive medical intervention. Uses pulmonary index scoring rather than peak flow to measure respiritory function.
			Requirement for supplemental oxygen	No significant difference
			Length of stay in the ED	No significant difference
			Number of patients admitted to hospital	No significant difference
			Length of Hospital stay for those admitted	No significant difference
B. Kjellman, H. Tollig and G. Wettrell 1980 Sweden	Ten children (7-16) with stable subacute asthma (FEV1 <70% predicited), 2 days post admission for acute asthma.	10 children, each acting as their own controll. FEV1 measured pre-and post either salbutamol nebuliser (2 administrations per day) or epinephrine nebuliser (2 administrations per day).	Change in FEV1	No difference between nebulised salbutamol and nebulised epinephrine	Small number of patients. Not acute asthma Only looked at FEV1, not the clinical effect on the child.

Comment(s)

In acute bronchiolitis, the alpha agonist effect of epinephrine is thought to reduce mucosal oedema in the bronchioles, whilst the beta agonist effect reduces smooth muscle spasm. It was postulated that this dual effect may be beneficial in acute asthma. Although this dual effect can be shown in vitro, it does not seem to be significant clinically. Inhaled salbutamol was introduced to replace subcutaneous epinephrine in acute asthma and was shown to be as effective. It seems that there is no additional benefit from inhaling epinephrine.

Clinical Bottom Line

There is no evidence that nebulised epinephrine is superior to nebulised salbutamol in childhood acute asthma.

References

1. Amy C. Plint, Martin H. Osmond, Terry P. Klassen The Efficacy of Nebulised Racemic Epinephrine in Children with Acute Asthma: A Randomised, Double-blind Trial Academic Emergency Medicine 2000 Oct;7(10) 1097-1103
2. B. Kjellman, H. Tollig and G. Wettrell Inhalation of Racemic Epinephrine in Children with Asthma Allergy 1980;35 605-610