Cochrane Review: Nebulized epinephrine for croup in children
Authors: Bjornson Candice , Russell Kelly F , Vandermeer Ben , Durec Tamara , Klassen Terry P , Johnson David W 
Published: July 2012

Background

Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine (NE) may prevent intubation.

Objectives

To evaluate the efficacy and safety of NE in children presenting to emergency department (ED) or admitted to hospital with croup.

Search methods

We searched CENTRAL (The Cochrane Library 2010, Issue 4), containing the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (1966 to November Week 1, 2010), EMBASE (1980 to November 2010), Web of Science (1974 to November 2010), CINAHL (1982 to November 2010) and Scopus (1996 to November 2010).

Selection criteria

Randomized controlled trials (RCTs) or quasi‐RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: NE versus placebo, racemic NE versus L‐epinephrine (an isomer), and NE delivered by intermittent positive pressure breathing (IPPB) versus NE without IPPB. Primary outcome was change in croup score post‐treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects.

Data collection and analysis

Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodologic quality assessment. One author extracted data while the second checked accuracy. We performed standard statistical analyses.

Main results

Eight studies (225 participants) were included. NE was associated with croup score improvement 30 minutes post‐treatment (three RCTs, standardized mean difference (SMD) ‐0.94; 95% confidence interval (CI) ‐1.37 to ‐0.51; I2 statistic = 0%). This effect was not significant two and six hours post‐treatment. NE was associated with significantly shorter hospital stay than placebo (one RCT, mean difference ‐32.0 hours; 95% CI ‐59.1 to ‐4.9). Comparing racemic and L‐epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI ‐0.42 to 1.08). After two hours, L‐epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of NE via IPPB versus nebulization alone at 30 minutes (one RCT, SMD ‐0.14; 95% CI ‐1.24 to 0.95) or two hours (SMD ‐0.72; 95% CI ‐1.86 to 0.42).

Authors' conclusions

NE is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post‐treatment. Evidence does not favor racemic epinephrine or LE, or IPPB over simple nebulization.

Plain Language Summary

Nebulized epinephrine for croup in children

Croup is a common childhood illness that is usually caused by a viral infection. Symptoms of croup include a hoarse voice, a 'barking' cough and noisy breathing. These symptoms are the result of swelling that occurs in the area of the windpipe (trachea) just below the voice box (larynx). Although most cases of croup are mild and resolve on their own, occasionally the swelling can be severe enough to cause difficulty in breathing. In these children, epinephrine (also called adrenaline) is a medication that is inhaled as a mist to temporarily shrink the swollen area in the trachea.

This review looked at trials of inhaled epinephrine for the treatment of children with croup. Compared to no medication, inhaled epinephrine improved croup symptoms in children at 30 minutes following treatment (three studies, 94 children). This treatment effect disappeared two hours after treatment (one study, 20 children). However, children's symptoms did not become worse than prior to treatment. No study measured adverse events. This review is comprised of only eight studies and the number of included children was small (225). Few studies examined similar outcomes, therefore data could often not be pooled and conclusions are based on one or few studies.