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Highlight for Query ‹Bluetongue symptoms

Rebound stridor in children with croup after nebulised adrenaline: does it really exist?

Search question

Do children with croup (patient group) when treated with nebulised adrenaline (intervention) develop re-emergence of stridor, worse than the initial baseline presentation (comparison) as defined by changes in symptoms score (outcome)?

Search strategy

Secondary sources: the Cochrane library was searched in September 2018 with the terms Croup and Adrenaline OR Epinephrine. One relevant review was identified. The review included eight studies. Primary sources: MEDLINE was searched via PubMed using following terms Croup OR Laryngitis AND Adrenaline OR Epinephrine OR rebound stridor. Inclusion criteria were that studies included children between the ages of 0 and 18 years. 41 clinical trials were retrieved. A further two studies [12, 13] were considered relevant, in addition to the eight studies included in the Cochrane review. Summaries of the papers are presented in the table 1.


The management of children with croup has had several controversies over the decades. In 1988, a review by Couriel emphasised the lack of high-quality studies to aid management. Nebulised adrenaline was advocated only in children with impending airway obstruction, due to the transient improvement and possibility of rebound. The benefit of steroids in the management was not clearly established at that time and hence most early studies compared treatments of nebulised adrenaline with placebo or racemic adrenaline versus


Lenny and Milner proposed the possibility of rebound phenomenon in children with acute viral croup treated with a nebulised α-adrenergic stimulant. The authors studied the total airway resistance before and after administration of nebulised phenylephrine in eight children. Prior to nebulisation, two drops of 0.05% xylometazoline were instilled in each nostril to ensure full nasal patency and children were sedated with 80 mg·kg−1 chloral hydrate. Seven out of eight children who were treated with nebulised phenylephrine showed improvement clinically and in terms of airway resistance. One child who did not show improvement was later was diagnosed with acute epiglottitis. The authors reported that improvement was transient and the airway resistance returned to pre-treatment levels within 30 min, which was hypothesised as a possible rebound phenomenon.

Over the following 40 years, the 10 studies identified here are very reassuring in that rebound does not exist and that although symptoms may return after the use of nebulised adrenaline, no study has reported the symptoms as being worse than baseline. If steroids are used as well then, as their effect starts to impact the upper airway at 2 h post-administration, this reduces any re-emergence of symptoms post-adrenaline as that effect wears off after 1–2 h.

A small underpowered study from 1973 by Gardner

et al., reported before the advent of the widespread use of steroids, was a retrospective review and this, not surprisingly, failed to substantiate a decrease in either hospitalisation or symptoms resulting from treatment with nebulised adrenaline. They did, however, acknowledge that adrenaline may be of therapeutic value in some patients with croup depending on the aetiological agent but may simply be the addition of moisture to the airways.

Three small studies [17–19], involving 48 children in total, showed significant initial improvement using nebulised adrenaline compared to placebo with some return of symptoms but no rebound reported. The following studies started using steroids in their design and recruited larger numbers but in children with more severe croup. No rebound of symptoms is described and an effect of the steroids reducing any re-emergence of symptoms is becoming clearer [7, 15, 16] (see table 1).


et al. reported re-emergence of symptoms in 35% of children receiving nebulised adrenaline and in 25% of children receiving placebo. No steroids were used. They posited that it is not likely that the phenomenon is related to adrenaline only, but rather to ongoing inflammation and oedema in the airway. They concluded that nebulised adrenaline is effective for the treatment of acute mild to moderately severe croup and that it should be used as a first line treatment. This has not been taken up universally, but it is now standard practice in some countries to use steroids and nebulised adrenaline in the emergency department, watch the patients for 2 h and then discharge home if well enough. The final two studies both used steroids and nebulised adrenaline, showing clearly a good response to the treatment with no rebound or indeed any major re-emergence of symptoms [12, 13].

The data presented here are reassuring in that re-emergence of symptoms may occur but is no worse than baseline. The re-emergence of symptoms is less marked in studies when children received concurrent steroids.

So, in answer to the proposed question: “Do children with croup (patient group) when treated with nebulised adrenaline (intervention) develop re-emergence of stridor, worse than initial baseline presentation (comparison) as defined by changes in symptoms score (outcome)?” Or “Rebound stridor in children with croup after nebulised adrenaline: does it really exist?” The answer is no.