Journal of Paediatric Respirology and Critical Care
Evidence based management of acute bronchiolitis
Sou-Chi SIT Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong
Bronchiolitis is a common acute lower respiratory tract
routine use of salbutamol is not recommended judging
disease affecting infants. It is associated with viral
infection and respiratory syncytial virus is the mostfrequently identified microorganism. Bronchiolitis
As compared with salbutamol, ipratropium bromide
remains one of the major reason for hospitalisation
is less controversial. No significant effect on the
in children younger than 1-year. Its presentation is
clinical outcomes was documented with ipratropium
characterised by fever, coryza, cough, expiratory
bromide in two systemic reviews by Schindler et al
wheezing and distress. There were numerous clinical
and King et al respectively.4,5 Therefore, use of
s t u d i e s p u b l i s h e d o n t h e e ff i c a c y o f v a r i o u s
ipratropium bromide in bronchiolitis is not advised.
medications used in managing this disease. However,the results of many of these studies were conflicting. Epinephrine
Hence, controversies still exist concerning thepharmacological treatment of bronchiolitis. In this
A recently published meta-analysis by Hartling et al
article, the current evidence from the recently
investigated the efficacy of epinephrine in treating
published literature on different drugs given for acute
bronchiolitis.6 Fourteen randomised controlled trial
bronchiolitis will be discussed. These include
were included of which they were further categorised
salbutamol, ipratopium bromide, epinephrine, steroid,
into inpatient and outpatient studies for analysis.
Clinical score was the only outcome found to befavouring epinephrine with the standardised mean
Bronchodilator
difference (SMD) of -0.52 (CI -1.00, -0.03) among theinpatient studies comparing epinephrine and placebo.
There were four meta-analyses and one systemic
For the outpatient studies (3 trials), 5 outcomes
review investigating the efficacy of bronchodiliators
including the clinical score at 60 minutes, change in
in treating bronchiolitis. Salbutamol was the most
oxygen saturation at 30 minutes, respiratory rate at
frequently used bronchodilator among the clinical
30 minutes and improvement favoured epinephrine.
studies. Kellner et al found in his two meta-analyses
There was no significant difference in admission rate
that bronchodilator produced short term improvement
between the treatment and control group. The authors
in the clinical score.1,2 Its administration was not
also compared the effect of epinephrine and
associated with any significant adverse effect.
salbutamol in both inpatient and outpatient studies.
However, the magnitude of reduction in clinical score
Respiratory rate at 30 minutes was the only outcome
was small between the treatment and control group
out of seven detected to be improved in the adrenaline
(pooled difference in clinical score -0.2; 95% CI -0.37
group with weighted mean difference of -5.12 (95%
to -0.1). The clinical importance is therefore
CI -6.83, -3.41). Among the four outpatient studies,
questionable. There was also no significant difference
change in oxygen saturation at 60 minutes, heart rate
observed in the rate and duration of hospitalisation
at 90 minutes, respiratory rate at 60 minutes and
between both groups. For the remaining three studies,
"improvement" favoured epinephrine over salbutamol.
the authors did not find any evidence to suggest that
The evidence is not sufficient to support use of
use of salbutamol was associated with consistent
epinephrine in the treatment of bronchiolitis among
c l i n i c a l i m p r o v e m e n t i n h o s p i t a l i s a t i o n r a t e ,
inpatients. There is some evidence to suggest the
physiological parameters or clinical scores.3-5 Thus,
efficacy of epinephrine among outpatients but all thestudies only investigated short term effect. A largeand high quality trials is needed to substantiate the
Author to whom correspondence should be addressed.
effect of epinephrine. Meanwhile, use of nebulised
epinephrine should not be routinely recommended.
steroid in managing severe bronchiolitis. Owing to theconflicting evidence, steroid should only be given to
The trials for steroid in the management of acute
patients with severe bronchiolitis after careful
bronchiolitis can be classified according to the types
of patients involved in the studies namely inpatients,outpatients and intensive care patients. Ribavirin
A meta-analysis by Garrison et al concluded that
A recent systemic review by King and his colleagues
systemic steroid was beneficial for treatment of
included 10 trials to investigate the effect of ribavirin
bronchiolitis by demonstrating improvement in length
for treatment of bronchiolitis.5 No significant difference
of stay and duration of symptoms.7 However, five out
on days of hospitalisation, length of time for intensive
of six included studies showed little or no beneficial
supportive interventions and duration of illness was
effect and the actual benefit demonstrated was
detected. Three out of six trials reporting clinical score
qualitatively small, i.e. less than half a day difference
and symptoms as their outcome did not find any
in hospitalisation. Hence, the result of this meta-
improvement after treatment with ribavirin. The results
analysis should be interpreted cautiously. In addition,
of the remaining three trials reporting positive effect
two other inpatient trials published in recent few years
were not entirely consistent. The authors therefore
failed to document any positive effect with the use of
concluded that no evidence of ribavirin use led to
steroid.8,9 There is currently inadequate evidence to
consistent or more than transient improvements in
support routine use of steroid in hospitalised patients
In another systemic review published in Cochrane
In contrast to the inpatient studies, three recently
Library 2004, the investigators found reduction in
published trials performed in the emergency
mortality (OR 0.58; 95% CI 0.18 to 1.85), probability
department have shown that systemic steroid was
of respiratory deterioration (OR 0.37; 95% CI 0.12 to
effective in reduction of clinical score, duration of
1.18), days of hospitalisation (weight mean difference
symptoms and hospitalisation.10-12 The corticosteroid
(WMD) of 1.9 days; 95% CI -4.6 to +0.9) and days of
used in the trials included 2 mg/kg of prednisolone
ventilation (WMD of 1.8 days; 95% CI -3.4 to -0.2) in
for 3 to 5 days and one dose of 1 mg/kg of dexa-
infants and young children with respiratory syncytial
methasone. Weinberger et al commented that the
virus infection of the lower respiratory tract with the
observed effect could have been explained by the
use of ribavirin.17 However, the included trials were
early treatment provided in the emergency department
small and lacked sufficient power to provide reliable
when the inflammation of airway was still reversible.13
estimate of the effects. A large RCT on ribavirin
A large and well designed RCT is certainly required
treatment for severe bronchiolitis is indicated to further
to confirm the efficacy on early initiation of steroid
therapy. Though, the existing evidence may not besufficient to recommend routine administration of
Montelukast
steroid to patients with bronchiolitis in the outpatientsetting, its use may be considered taking into account
Bisgaard and his groups described their observation
on the effect of montelukast on symptoms of RSVbronchiolitis.18 Infants were free of any symptoms on
In the subgroup analysis of two separate studies by
22% of the days and nights after receiving 28 days of
van Woensel et al, systemic steroid shortened the
montelukast therapy whereas patients on placebo had
duration of mechanical ventilation, supplemental
4% of symptom-free days and nights (p=0.015). Also,
oxygen and hospital stay in bronchiolitis patients
the day time cough was reduced and exacerbation
requiring mechanical ventilation.14,15 However, another
was delayed significantly in the montelukast-treated
trial performed on critical ill patients with bronchiolitis
group. However, this study was designed to evaluate
did not detect any significant difference in clinical
the treatment effect on postbronchiolitis symptom and
outcomes of the steroid treated group.16 Further large
its role on acute symptom has not been addressed.
scale trial is warranted to document the benefit of
To date, this study is the only trial reporting the use
Journal of Paediatric Respirology and Critical Care
of montelukast in the management of bronchiolitis.
CS, et al. Long and short-term effect of prednisolone in
More studies are needed to determine the efficacy of
hospitalized infants with acute bronchiolitis. J Paediatr Child
montelukast on acute symptoms of bronchiolitis before
any recommendation can be made on its use.
10. Goebel J, Estrada B, Quinonez J, Nagji N, Sanford D,
Boerth RC. Prednisolone plus albuterol versus albuterolalone in mild to moderate bronchiolitis. Clin Pediatr (Phila)
In summary, many studies identified for drugs given
in bronchiolitis were underpowered and their results
11. Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M, et
were not uncommonly conflicting. Large trials on
al. Efficacy of oral dexamethasone in outpatients with acute
individual medications are definitely indicated to
bronchiolitis. J Pediatr 2002;140:27-32.
provide clinicians with adequate guidance for an
12. Csonka P, Kaila M, Laippala P, Iso-Mustajarvi M, Vesikari
evidence based approach in management of this
T, Ashorn P. Oral prednisolone in the acute management
common disease of paediatric patients.
of children age 6 to 35 months with viral respiratoryinfection-induced lower airway disease: a randomized,
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PRENATAL DIAGNOSIS Prenat Diagn 2009; 29 : 1095–1096. Published online in Wiley InterScience (www.interscience.wiley.com) CORRESPONDENCE Antibiotic prophylaxis before amniocentesis: a proven and effective method to preserve fetal life APGA trial (Giorlandino et al ., 2009) is today theAlfirevic and Pilu point out the attention on a cru-biggest randomized controlled trial (RCT) ever
Ultrasound Obstet Gynecol 2013; 42 : 478–479 Published online 8 May 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.12366 How to . . . Practical advice on imaging-based techniques and investigations withaccompanying slides and videoclips online How to record uterine artery Doppler in the first trimester *Department of Fetal Medicine, Institute for Women’s