This randomized controlled trial compared 7%
hypertonic saline versus 0.9% (normal) saline, in addition to racemic
epinephrine (in both groups), among infants with mild to moderate
severity bronchiolitis. The authors used a modification of the
oft-applied bronchiolitis severity score (BSS) by Wang, et al.
 to evaluate the efficacy of treatment at multiple time points until
discharge/disposition from the hospital. They reported no statistically
significant differences between the groups for changes in modified-BSS
after 1 dose of treatment as well as until final disposition from the
This study has the usual methodological refinements
associated with a high-quality trial, including appropriate sequence
generation, block randomization, allocation concealment and
double-blinding (especially the outcome assessor). Although a
convenience sample was enrolled, the number included was pre-calculated
and adequately powered. The cohort of infants was consistent with the
usual clinical understanding of bronchiolitis. Clinically relevant
outcomes were chosen for evaluation of efficacy.
Some years back, Indian Pediatrics explored
the issue of hypertonic saline as an adjunct therapy in bronchiolitis
, and concluded that there was insufficient robust evidence to
include it in routine practice. However, a Cochrane systematic review
 published around the same time suggested a beneficial effect of
hypertonic saline in terms of statistically significant reduction in
clinical severity score and duration of hospital stay. At that time, all
available studies had compared 3% hypertonic saline against normal
saline. There is a single recent trial that used 5% hypertonic saline in
some patients  but results are presented together with those
receiving 3% saline. In that sense, this trial by Jacobs, et al.
evaluating 7% hypertonic saline is the first of its kind. In fact, the
authors have used this to justify their trial, expecting that 7% saline
would be even more beneficial than 3% saline.
It is therefore surprising that Jacobs, et al.
failed to mention the updated version of the Cochrane review published
in May 2013  that included a total of 11 trials. This review
corroborated the previous version, again showing a statistically
significant reduction in severity score and hospital stay. Strictly
speaking, the trial by Jacobs, et al. may not be comparable to
the trials included in the Cochrane review, as the intervention and the
measurement tool for outcomes were different. However, the benefit of
alluding to it would have been to report the findings using the same
tools for outcome measurement as all the previous trials. This would
have made it possible to incorporate Jacobs’ findings into the
meta-analysis and assess its impact on the results available thus far.
This trial suggests that 7% hypertonic saline added
to epinephrine may not provide additional benefit in bronchiolitis,
although the balance of evidence is leaning towards adding 3% hypertonic
saline to epinephrine for infants with bronchiolitis. The implications
for research are two-fold viz that additional randomized trials may be
required to resolve the issue and more important – new research should
be conducted with an attempt to enrich existing knowledge, rather than
for the sake of research itself.
Jospeh L Mathew
Department of Pediatrics,
PGIMER, Chandigarh, India.
Pediatric Pulmonologist’s Viewpoint
The debate on bronchiolitis and its management will
remain a controversy for many years to come and the final word might be
difficult to arrive at – with the present background. Bronchiolitis is
defined as a clinical syndrome in children less than 2 years of age,
characterized by upper respiratory tract symptoms followed by lower
respiratory tract signs and symptoms – with no other explanation for the
wheezing. However, the first episode of wheeze can be an overlap
manifestation of episodic virus-induced wheezing or acute
viral-triggered asthma. It is pertinent to remember that all first
episodes of wheeze in young children within the agreed clinical
definition are only "probable bronchiolits".
Inhaled epinephrine for bronchiolitis was found to be
of benefit in the first day of care . Nebulized 3% saline
significantly reduces clinical severity score and also the length of
hospital stay among children with non-severe acute bronchiolitis .
However a recent randomized control study in Indian context failed to
elicit a favorable response . In Indian children with cystic
fibrosis, 3% hypertonic saline nebulization was better than 7% saline
inhalation as a mucolytic .
A major hurdle in an interventional study is the
difficulty to differentiate bronchiolitis from virus-induced wheeze or
asthma, as each category responds differently making it difficult to
determine the effect of each medication. Further, presence of two drugs
– that could have a synergistic or antagonistic effect – makes the
assessment of the effect of a single drug in such combination difficult.
The present study is thought-provoking by being the first study with 7%
saline. In clinical practice, 3% saline would remain the preferred
choice when warranted. The use of 7% saline as a concept is interesting,
but for now – is not promising.
Consultant Pediatrician and Pulmonologist,
Sundaram Medical Foundation,
Dr Rangarajan Memorial Hospital,
Chennai, Tamil Nadu, India.
Given that bronchiolitis is one of those illnesses of
infancy in which the treating physician is almost helpless and at
his/her wit’s end – being unable to provide any definitive treatment to
alleviate the symptoms – a new treatment modality is welcome. Over the
past decades, proven effective treatments for bronchiolitis remain the
same: oxygen and hydration. Routine use of corticosteroids or
bronchodilators has no proven efficacy, although a trial of
bronchodilators is worth a try. Evidence suggests that epinephrine may
be more efficacious compared to salbutamol.
Nebulized hypertonic saline has shown promise as an
alternative treatment option. The majority of studies are with 3% saline
and some with 5% saline, either alone or in combination with
epinephrine. The most recent Cochrane review  of this treatment
modality suggests a definite advantage with reduced length of
hospitalization in moderate to severe bronchiolitis and some improvement
in clinical scores. No adverse effects with nebulized hypertonic saline
have been reported. As far as 7% saline goes, this seems to be the first
study to evaluate its efficacy in bronchiolitis: it does not show any
additional benefit compared to nebulization with normal saline and
epinephrine. Nebulized 7% saline has also not shown any additional
benefit in patients with cystic fibrosis . For infants hospitalized
with bronchiolitis, the most justifiable and safe treatment option
(apart from supportive treatment with oxygen and intravenous fluids) may
be a trial of nebulized epinephrine with 3% saline that is to be
continued if a definite objective improvement is demonstrated.
Max Healthcare, New Delhi, India.
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