Table 1.

Summary of the 10 articles examining re-emergence of symptoms after nebulised adrenaline use in croup

Citation [ref.], year	Study population	Study type	Outcome	Comments
Eghbali [12], 2016	174 children between age of 6 months and 6 years. 87 children received placebo and 87 children received nebulised l-adrenaline (0.5 mg·kg−1 per dose). A single dose of i.m. dexamethasone 0.6 mg·kg−1 (maximum 8 mg) was administered to all.	Randomised double blind clinical trial	Significant reduction in mean croup score (Westley croup score) in children who received l-adrenaline (p<0.009).	Children treated with nebulised l-adrenaline showed continued decrease in croup score until 120 min.No rebound effect demonstrated in both study groups.
Weber [13], 2001	29 children with moderate to severe croup (modified Taussig croup score >5). Cool humidified oxygen and i.m. dexamethasone 0.6 mg·kg−1 administered to all children. 15 children randomised to nebulised racemic adrenaline 0.5 mL in 2.5 mL of normal saline for 3 h. 14 children randomised to 3 h of Heliox (blend of 70% helium and 30% oxygen) gas therapy for 3 h, with nebulised saline as placebo.	Randomised double blind clinical trial	Improvement in croup scores in both groups, with no overall statistically significant difference.	No deterioration of croup score to above score at presentation.
Kristjansson [14], 1994	54 children with mild to moderate croup. 25 children received racemic adrenaline and 29 children placebo.	Randomised double blind clinical trial	Children in both groups showed improvement.Children who received racemic adrenaline were significantly better than placebo in terms of improvement in total clinical score, inspiratory stridor, retractions and air entry. Relapse phenomenon was seen in 35% of children in the treatment group and 25% in placebo group. No child was clinically worse at 2 h after treatment than before treatment.	Authors reported relapse rather than rebound. The re-emergence of symptoms was higher in adrenaline group than placebo, but symptoms were no worse than baseline.
Fernandez [15], 1993	66 children hospitalised for croup. Children were randomised into four groups. Group 1: nebulised l-adrenaline and placebo (i.m.). Group 2: nebulised saline and placebo (i.m.). Group 3: nebulised saline and dexamethasone (i.m.). Group 4: nebulised l-adrenaline and dexamethasone (i.m.).	Randomised double blind clinical trial	Nebulised adrenaline was more beneficial than saline (p<0.05). No statistically significant improvement in the group treated with dexamethasone when compared with the group treated with the placebo i.m. injection.	No deterioration of croup score to above the score at presentation.
Waisman [7], 1992	Children between 6 months and 6 years of age with modified Downes and Rahaely Raphaely score>6. 16 children randomised to receive racemic nebulised adrenaline and 15 nebulised l-adrenaline. i.m. dexamethasone 0.6 mg·kg−1 given to children with a score >8.	Randomised double blind clinical trial	Significant reduction in croup scores in both groups at 30 min.	Re-emergence of croup symptoms with slight increase in croup scores at 60 min but no worse than baseline.
Kuusela [16], 1988	72 children hospitalised for croup were randomised to receive a single dose of 0.6 mg·kg−1 of i.m. dexamethasone or placebo. Subsequently the same patients were randomised to receive either nebulised racemic adrenaline or saline by inhalation.	Randomised double blind clinical trial	Children who received dexamethasone and racemic adrenaline had the lowest scores by all evaluations at 6 and 12 h. Only cough score at 6 h was significantly better in dexamethasone and racemic adrenaline group than the dexamethasone and saline group.	The authors conclude that a single i.m. injection of dexamethasone is beneficial in acute spasmodic croup. Nebulised racemic adrenaline is also effective, but the effect is less remarkable in patients treated with dexamethasone. The study does not provide clinical data at 30 min or 60 min when racemic adrenaline is likely to be beneficial.
Fogel [17], 1982	14 children with croup who had persistent inspiratory stridor at rest 20–30 min after sterile saline mist therapy were randomised to receive racemic adrenaline by nebulisation alone or racemic adrenaline by nebulisation with IPPB.	Randomised double blind clinical trial	Highly significant reduction in croup score (p<0.001) in both groups at 30 and 60 min, but no significant difference at 90 and 120 min.	None of the children received steroids. No deterioration of croup score to above the score at presentation.
Corkey [18], 1981	14 hospitalised children with acute infectious croup were randomised to receive nebulised distilled water (group I) or racemic adrenaline (group II).	Randomised double blind clinical trial	Group II children who received racemic adrenaline showed a statistically significant improvement (p<0.005) in both objective radiological assessment of tracheal diameter and subjective clinical score.	None of the children received steroids. No deterioration of croup score to above the score at presentation.
Westley [19], 1978	20 hospitalised children between 4 months and 5  years with acute croup and persistent stridor at rest. 10 children randomised to receive 2.25% racemic adrenaline and 10 children received nebulised normal saline as placebo.	Randomised double blind clinical trial	Racemic adrenaline group showed significant reduction in mean croup score 10 and 30 min after treatment compared with placebo (p<0.01).	Authors report no statistically significant difference in croup score at 120 min; however, analysis of data shows that it was no worse than pre-treatment level.
Gardner [20], 1973	20 children evaluated. 10 received racemic adrenaline and 10 received placebo.	Controlled double blind trial	Of the 10 children who showed a significant improvement five received racemic adrenaline and five placebo. All three children who showed mild improvement had received racemic adrenaline. Of seven children who had no improvement two received racemic adrenaline and five received placebo.	The authors concluded that apparent effectiveness of racemic adrenaline might be related to nebulisation of moisture rather than direct effect of the drug. None of children received steroids. No deterioration of croup score to above the score at presentation.

i.m.: intramuscular; IPPB: intermittent positive pressure breathing.