Child Health Update

Nebulized epinephrine for

young children with bronchiolitis
Teeranai Sakulchit MD Ran D. Goldman MD FRCPC

Abstract
Question Every winter I see infants with flulike symptoms and wheezing. I frequently diagnose them with
bronchiolitis based on their presenting symptoms. Would it be prudent to send those infants to the nearest
emergency department for treatment with nebulized epinephrine?

Answer Nebulized epinephrine should not be routinely used in infants with bronchiolitis. It is an option to
consider in those with severe symptoms. If it is given and there are no signs of improvement, further doses
are discouraged. Ongoing studies of epinephrine combined with other agents (eg, hypertonic saline, oral
dexamethasone) are needed to confirm their benefit.

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La traduction en franais de cet article se trouve www.cfp.ca dans la table des matires du numro de dcembre 2016 la page e718.

B ronchiolitis is an acute inflammation of the bron-

chioles that leads to small airway edema, necro-
sis, and increased mucus production.1 It is triggered by
and reduction of airway edema,8 hence its potential role
in treatment of acute bronchiolitis.
Patel and colleagues9 from Canada assessed length
viral infections, most commonly respiratory syncytial of hospital stay in 149 term and healthy infants up to 12
virus,2 and affects children younger than age 2.3 Peak months of age who were admitted with a first episode of
incidence of bronchiolitis is between December and acute respiratory tract infection and wheezing. Infants
March in North America.4 Common presenting symp- receiving nebulized epinephrine (2.25% solution), alb-
toms include rhinorrhea and cough, followed by tachy- uterol (5 mg/mL solution), or saline placebo (0.9% sodium
pnea, nasal flaring, accessory muscles use, and, in some chloride) had similar lengths of stay (mean [SD] number
children, crackles and wheezing.5 The diagnosis is based of hours was 59.8 [62] for epinephrine, 61.4 [54] for alb-
on history and physical examination. Blood sampling uterol, and 63.3 [47] for placebo; P=.95). Similar find-
and chest radiography are rarely needed.1 ings were reported by Wainwright et al10 from Australia.
Treatment of bronchiolitis is mostly supportive and After administration of nebulized epinephrine or placebo,
includes suctioning of secretions, encouraging feeding, there was no difference found in length of hospital stay
and maintaining hydration. Other treatments include (P=.16) among 194 healthy infants with a first episode of
bronchodilators, corticosteroids, and nebulized hyper- wheezing and a clinical diagnosis of bronchiolitis. These
tonic saline. However, according to guidelines by the 2 studies were included in a systematic review,11 which
American Academy of Pediatrics 1 and the Canadian concluded that nebulized epinephrine and saline placebo
Paediatric Society,6 albuterol or salbutamol and systemic had similar effects on admission length (mean difference
corticosteroids should not be prescribed to infants with -0.35 days; 95% CI -0.87 to 0.17 days).
bronchiolitis. Although nebulized hypertonic saline is A following study from Norway12 confirmed the lack of
not recommended in the emergency setting, it might be epinephrine effect on length of hospital stay among 404
considered in hospitalized infants with bronchiolitis.7 infants with moderate to severe bronchiolitis (racemic
Supplemental oxygen is recommended for children who epinephrine dissolved in 0.9% saline vs 0.9% saline alone;
present with an oxygen saturation of less than 90%.1,6 P>.43). Hospital admission was longer if inhaled epi-
Hand washing has been identified as the most important nephrine was given on a fixed schedule compared with
measure to prevent dissemination of the disease. an on demand schedule (61.3 hours, 95% CI 45.4 to 77.2
hours vs 47.6 hours, 95% CI 30.6 to 64.6 hours; P=.01).
Nebulized epinephrine for inpatients
Epinephrine is a mixed - and -adrenergic agonist. The Combined epinephrine and hypertonic saline
-adrenergic action is responsible for vasoconstriction Evidence on the effect of nebulized hypertonic saline

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Child Health Update

in infants with bronchiolitis is conflicting,13 and some In another large Canadian study, 20800 term and
research suggests it might reduce length of hospital stay healthy infants (6 weeks to 12 months of age) with mod-
for children hospitalized for more than 3 days.7 It was erate bronchiolitis who visited 8 pediatric EDs during the
suggested that a combination of epinephrine and hyper- peak respiratory syncytial virus season received nebulized
tonic saline might be of benefit to admitted children. epinephrine and oral dexamethasone (group 1), nebu-
Among 185 term and healthy infants (younger than lized epinephrine with oral placebo (group 2), nebulized
age 24 months) with moderate bronchiolitis admitted to placebo with oral dexamethasone (group 3), or nebulized
a Spanish hospital, investigators administered nebulized placebo with oral placebo (group 4). The 2 nebulized treat-
3% hypertonic saline with either a 3-mL epinephrine or ments administered 30 minutes apart consisted of 3 mL
3-mL placebo (ie, sterile water) combination.14 Infants of 1:1000 epinephrine or saline. The oral treatment con-
improved significantly earlier in the epinephrine group sisted of 1 mg/kg of dexamethasone (maximum 10 mg)
(P=.029 and P=.036 on days 3 and 5, respectively), and or placebo given after the first nebulized treatment in
length of hospital stay was significantly shorter in the the ED, followed by once-daily doses of dexamethasone
epinephrine group compared with those receiving pla- (0.6 mg/kg) or placebo for 5 days. Infants receiving epi-
cebo (mean [SD] of 3.9 [1.9] vs 4.8 [2.3] days; P=.011). nephrine and dexamethasone had lower ED admission
On the contrary, in a small study from Tunisia15 with 94 rates compared with those receiving placebo by day
term infants (up to 12 months old) with a first episode of 7 (RR=0.65; 95% CI 0.45 to 0.95; P=.02; unadjusted anal-
moderate acute bronchiolitis, length of hospital stay in ysis). However, after adjusted analysis owing to multi-
infants who received a combination of 2 mL of epineph- ple comparisons, the RR of ED admission by day 7 in the
rine and 2 mL of 5% hypertonic saline every 4 hours was group receiving epinephrine with dexamethasone com-
similar to those who received hypertonic saline alone or pared with the group receiving placebo was no longer
with saline placebo (mean [SD] of 3.5 [2.0], 3.6 [1.7], and significant (95% CI 0.41 to 1.04; P=.07). Nebulized epineph-
4.5 [3.8] days, respectively; P=.316). rine or oral dexamethasone alone did not reduce the rate
While the Spanish study provides a compelling of admission compared with placebo in both unadjusted
argument to use a combination of epinephrine and and adjusted analysis. Nebulized epinephrine seems to
hypertonic saline, it is premature to recommend such have only a transient effect on preventing ED admission.
treatment, and larger studies repeating these findings Further studies are needed to confirm this result.
are needed to endorse such therapy.
Conclusion
Nebulized epinephrine for outpatients Nebulized epinephrine should not be used in hospital-
While findings among admitted infants show a lack of ized children except if used as a rescue agent for severe
sufficient response to nebulized epinephrine, emer- diseasemarkedly increased respiratory rate, retrac-
gency department (ED) research investigated the ben- tions, and decreased oxygen saturation. For children
efit of early epinephrine therapy in the ED. A Cochrane seen in the ED, evidence does not support the effec-
review11 included 5 studies16-20 with 995 children who tiveness of nebulized epinephrine in infants with bron-
received nebulized epinephrine versus saline placebo. chiolitis. For children with severe illness, providers can
Cumulative evidence documented a significantly lower administer a dose of epinephrine and carefully moni-
admission rate at day 1 after the ED visit among those tor for possible improvement. If there are no signs of
receiving epinephrine (relative risk [RR] of 0.67; 95% CI improvement, further doses are discouraged. The combi-
0.50 to 0.89), a benefit lost by day 7 after the ED visit nation of epinephrine with other agents (eg, hypertonic
(RR=0.81; 95% CI 0.63 to 1.03). Out of those 5 stud- saline or oral dexamethasone) needs further research in
ies, 219,20 declared admission rate as a primary outcome order to confirm any benefit.
while the other studies used clinical score as the primary Competing interests
None declared
outcome and admission rate as the secondary outcome.
Correspondence
When nebulized racemic epinephrine was com- Dr Ran D. Goldman; e-mail [email protected]
pared with albuterol and saline placebo in the treat- References
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992 Canadian Family Physician Le Mdecin de famille canadien | Vol 62: december dcembre 2016
 Child Health Update

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Do you have questions about the effects of drugs, chemicals, radiation, or
ized, controlled trial of nebulized 5% hypertonic saline and mixed 5% hyper- infections in children? We invite you to submit them to the PRETx program by
tonic saline with epinephrine in bronchiolitis. Tunis Med 2014;92(11):674-7. fax at 604 875-2414; they will be addressed in future Child Health Updates.
16. Anil AB, Anil M, Saglam AB, Cetin N, Bal A, Aksu N. High volume normal saline
alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal Published Child Health Updates are available on the Canadian Family Physician
saline, and 3% saline in mild bronchiolitis. Pediatr Pulmonol 2010;45(1):41-7. website (www.cfp.ca).

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