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A 4 month old infant attends the emergency department in the late morning with bronchiolitis. It is the first episode of wheeze. Clinically, there is moderate indrawing and recession, tachypnoea (respiratory rate = 50), reasonable air movement on auscultation, and the oxygen saturation is 94% in air. You want to admit the infant, but the mother is breast feeding and keen to get home by 3 pm, when her other children get home from school. You have heard that in North America, nebulised adrenaline has been used in some cases and admission has been avoided.
Structured clinical question
In an infant with bronchiolitis [patient] does nebulised adrenaline (compared to other treatments) [intervention] reduce the need for admission [outcome]?
Cochrane Library (2002)—“bronchiolitis”—4 systematic reviews (3 irrelevant—anticholinergics and wheeze, ribavirin, immunoglobulin); 1 protocol.
Clinical Evidence (Issue 7)—“child health—bronchiolitis”—2 systematic reviews (1 irrelevant—adrenaline not included) and 1 protocol for SR.
DARE—“bronchiolitis”—8 systematic reviews (5 irrelevant; 2 relevant SRs were by same authors—1 referenced in Cochrane and 1 referenced in journal; 1 protocol).
PubMed clinical queries
“bronchiolitis” and “epinephrine” [therapy, sensitive]—33 references (23 irrelevant to question). Of 10 relevant, 2 not randomised controlled trials.
MedLine [1966–Dec, 2000] (Ovid)
“bronchiolitis” or “bronchitis” and [“epinephrine (exp)” or “catecholamines”]; LIMIT to “clinical trial”—23 references (14 irrelevant to question).
Nine papers addressed the question of nebulised adrenaline and bronchiolitis (two of them specifically answering the question). See table 1⇓.
There are only two studies (Menon et al and Ray and Singh) that specifically answer the question, and both of these studies show a reduction in hospital admission with adrenaline; the study groups are similar to the patient in the clinical scenario.
A systematic review that includes adrenaline as one of a number of bronchodilators fails to show significant differences in outcomes compared to placebo. However, adrenaline has an α adrenergic action that is thought to be important in bronchiolitis (as well as its β adrenergic bronchodilatation effects). The positive effect of adrenaline may therefore have been diluted in the systematic review by the inclusion of agents that have little or no effect. A systematic review on the effect of adrenaline in bronchiolitis is underway (protocol in Cochrane Library10).
The Menon and Ray studies compared adrenaline with salbutamol, which is not routinely used in the UK in this condition. For this reason, data on studies comparing adrenaline to placebo in bronchiolitis are also presented. Most studies comparing the two show a benefit of adrenaline over placebo as well as benefit over pure β adrenergic agonists. There are studies showing similar benefits with l-adrenaline as well as racemic adrenaline.
It is thought that the α adrenergic properties of adrenaline are important in bronchiolitis, as the vasoconstriction of the pulmonary vessels reduces mucosal oedema and exudate, thereby reducing airway obstruction.
Only one study (Abul-Ainine et al) failed to show a difference between adrenaline and placebo. Only one dose of adrenaline was used, however, which may be a reason for the lack of difference. Admission rates were not examined as all patients were admitted. This study does confirm the safety of adrenaline in this condition.
The regimes used were 3 ml of 1/1000 adrenaline nebulised at arrival and 30 minutes later, followed by observation for at least two hours (Menon et al); and 0.1 mg/kg/dose given at 20 minute intervals three times and then observation for three hours (Ray and Singh).
Currently, a multicentre trial in the UK comparing nebulised adrenaline with placebo is under discussion.
CLINICAL BOTTOM LINE
Nebulised adrenaline reduces hospital admission in bronchiolitis.
Nebulised adrenaline is superior to salbutamol and placebo in relieving symptoms in bronchiolitis.
Nebulised adrenaline is safe in bronchiolitis.