Study characteristics
Study/Country Population
Intervention
Comparator(s)
Outcomes (Primary, Secondary)
Al-Ansari 2010 et al /
Inclusion: Children under 18 months, diagnosed with acute
3% Hypertonic saline (HS) (5ml),
0.9% Normal saline (NS) (5ml)
Bronchiolitis severity score improvement at 48
Qatar (Single centre)
bronchiolitis, upper respiratory tract infection, wheezing
5% Hypertonic saline (HS) (5ml).
administered every 4 hours until they
hours, length of hospital stay, readmissions
[67]
and/or crackles on auscultation, BSS (> 4).
Administered every 4 hours until
were ready for discharge via a
within 7 days and adverse events.
Exclusion: <34 weeks gestation, history of wheezing,
they were ready for discharge, via
nebuliser (flow rate 10L/min).
steroid use within 48 hours, obtundation and progressive
a nebuliser (flow rate 10L/min).
Administered with 1.5ml epinephrine.
respiratory failure requiring ICU admission, apnea within 24
Administered with 1.5ml
hours, oxygen saturation <85% in air, chronic lung disease,
epinephrine.
congenital heart disease, immunodeficiency.
Espelt et al 2012 /
Inclusion: Infants aged 1 to 24 months, 1st episode of
3% Hypertonic saline (HS) (3ml),
0.9% saline (NS) (3ml), administered
Length of hospital stay and length of oxygen
Argentina (number of
bronchiolitis with clinical severity score of >5 and 02
administered 4 times per day over
4 times per day over 5 days via a
use.
centres unknown)
saturation of <97%.
5 days via a nebuliser.
nebuliser. Administered with 0.25
[25]
Exclusion: Chronic respiratory or cardiovascular disease,
Administered with 0.25 mg/kg
mg/kg Albuterol.
respiratory failure.
Albuterol.
Everard et al 2014 /
Inclusion: Previously healthy infants under 1 year of age,
3% Hypertonic Saline (HS) (4ml),
UK (Multi-centre)
admitted with acute bronchiolitis, oxygen saturation <92%
administered every 6 hours until
discharge (length of hospital stay), admission
[72]
in air, consented and randomised within 4 hours of
fit for discharge via PARI Sprint
to intensive care units, readmission rates,
admission by a medical paediatrician.
nebuliser (flow rate 5L/minute).
duration of respiratory symptoms within 28
Usual Care
Time to fit for discharge, time to actual
Exclusion: Wheezy bronchitis or asthma – children with an
days of randomisation, healthcare utilisation
apparent viral respiratory infection and wheeze with no or
within 28 days of randomisation, Infant and
occasional crepitations, reflux, previous lower respiratory
parental quality of life using the Infant Toddler
tract infections (requiring assessment in hospital), risk
Quality of Life (ITQoL) questionnaire at 28
factors for severe disease [gestation <32 weeks,
days following randomisation and adverse
immunodeficiency, neurological and cardiac conditions,
events.
chronic lung disease], subjects where the carer’s English is
not fluent and translational services are not available.
Giudice et al 2012 /
Inclusion: Children under 2 years, first episode of
3% Hypertonic saline (HS)
0.9% saline (NS), administered every
Length of hospital stay and clinical response
Italy (Single centre)
bronchiolitis, 02 saturation of <94% in room air, significant
administered every 6 hours via a
6 hours via a nebuliser (flow rate
determined using clinical severity scores.
[61]
respiratory distress (Wang CSS score).
nebuliser (flow rate 6L/min).
6L/min). Administered with
Exclusion: Pre-existing cardiac/pulmonary disease,
Administered with aerosolised
aerosolised epinephrine (1.5mg).
premature birth (<36 wks), previous asthma diagnosis,
epinephrine (1.5mg).
initial 02 stats less than 85% or respiratory distress requiring
resuscitation.
Kuzik et al 2007 /
Inclusion: children under 18 months, first episode of
3% Hypertonic saline (HS) (4ml)
0.9% saline (NS) (4ml), administered
Abu Dhabi and
bronchiolitis.
administered every 2 hours (3
every 2 hours (3 doses), every 4 hours
Canada (Multi
Exclusion: Previous history of wheezing, cardiopulmonary
doses), every 4 hours (5 doses),
(5 doses), every 6 hours till discharge
centre) [20]
disease or immunodeficiency, critical illness requiring
every 6 hours till discharge via a
via a nebuliser.
admission to ITU, use of nebulised HS in last 12 hrs or
nebuliser.
Length of hospital stay and adverse events.
premature birth (<34wks).
Luo et al 2010 / China
Inclusion: children under 2 years, first episode of viral
3% hypertonic saline (4ml), 3
0.9% saline (NS) (4ml), 3 Treatments
Length of hospital stay, cough and wheezing,
(Single centre) [62]
bronchiolitis, mild to moderate bronchiolitis.
Treatments every day every 8
every day every 8 hours until
pulmonary moist crackles remission time and
Exclusion: >24 months, previous wheezing episode, chronic
hours until discharge via a
discharge via a nebuliser.
adverse events.
cardiac or pulmonary disease, immunodeficiency,
nebuliser. Administered with 2.5
Administered with 2.5 mg salbutamol.
accompanying respiratory failure, requiring mechanical
mg salbutamol.
ventilation, having intervention 12 h before treatment,
premature infants.
Luo et al 2011 /
Inclusion: infants aged <24 months, first episode of
3% hypertonic saline (HS) (4ml),
0.9% saline (NS) (4ml), administered
Length of hospital stay, clinical severity scores
China (Single centre)
wheezing, admitted to hospital for treatment of moderate to
administered every 2 hours (3
every 2 hours (3 doses), every 4 hours
and remission of cough, wheezing, pulmonary
[63]
severe bronchiolitis.
doses), every 4 hours (5 doses),
(5 doses), every 6 hours till discharge
moist crackles and adverse events.
Exclusion: >24 months, previous episode of wheezing,
every 6 hours till discharge via a
via a nebuliser.
chronic cardiac and pulmonary disease, immunodeficiency,
nebuliser.
accompanying respiratory failure needing mechanical
ventilation, inhaled 3% HS 12 hours before treatment,
premature birth.
Maheshkumar et al
Inclusion: Children under 2 years, 1st episode of
3% Hypertonic saline (HS) (3ml),
Normal saline (NS) (3ml),
Length of hospital stay, reduction in clinical
2013 / India (Single
bronchiolitis, moderate distress.
administered every 6 hours till fit
administered every 6 hours till fit for
severity scores, number of add on nebulisations
centre) [66]
Exclusion: pre-existing cardiac disease, previous wheezing
for discharge, via a nebuliser (flow
discharge via a nebuliser (flow rate 5-
and number of treatment failures.
episode, severe disease (score of >8) needing mechanical
rate 5-6L/min). Administered with
6L/min). Administered with 0.15
ventilation, saturation <85% on room air, cyanosis,
0.15 mg/kg Salbutamol.
mg/kg Salbutamol.
obtunded consciousness and/or progressive respiratory
failure.
Mandelberg et al
Inclusion: children up to 12 months, viral bronchiolitis with
3% hypertonic saline (HS) (4ml),
0.9% saline (NS) (4ml), administered
Length of hospital stay, change in clinical
2003 / Israel (Single
temperature of >38 degrees C leading to hospitalisation.
administered 3 times a day every 8
3 times a day every 8 hours until
severity scores and adverse events.
centre) [18]
Exclusion: cardiac or chronic respiratory disease, previous
hours until ready for discharge via
ready for discharge via an aeromist
wheezing episode, saturation <85% in room air, obtunded
an aeromist nebuliser (flow rate
nebuliser (flow rate 5L/min).
consciousness, progressive respiratory failure needing
5L/min).Administered with 1.5 mg
Administered with 1.5 mg
mechanical ventilation.
epinephrine. Administered until
epinephrine. The nebuliser was
nebuliser empty.
administered until empty.
Nemsadze et al 2013
Children 2 months to 2 years old with bronchiolitis,
3% Hypertonic saline (HS),
Normal saline (NS) administered
Bronchiolitis Clinical Score, length of hospital
/ Georgia (Number of
eligibility criteria unclear as abstract only.
administered every 6 hours.
every 6 hours.
stay and change in oxygen saturation.
centres unknown)
[68]
Ojha et al 2014 /
Inclusion: Aged 6 weeks – 24 months, presenting with
3% Hypertonic Saline (HS) (4ml),
0.9% Normal Saline (NS) (4ml),
Length of hospital stay and requirement of
Nepal (Single centre)
bronchiolitis for the first time.
patients in each group received
patients in each group received
oxygen supplementation.
[71]
Exclusion: Previous episode of wheezing, chronic cardiac
minimum of three nebulization
minimum of three nebulisation each
and pulmonary disease, immunodeficiency, respiratory
each day delivered at 8 hour
day delivered at 8 hour intervals until
failure, mechanical ventilation, inhaling nebulised 3% saline
intervals until discharge via a
discharge via a nebuliser.
and salbultamol 12 hours before treatment, premature
nebuliser.
infants (less than 34 weeks), oxygen saturation below 85%
on room air.
Ozdogan et al 2014 /
Inclusion: Infants 1-24 months of age admitted to hospital
3% Hypertonic Saline (HS), 5%
0.9% normal saline (NS) administered
Change in respiratory score and length of
Turkey (Number of
with acute bronchiolitis.
Hypertonic Saline (HS).
via nebulisations given three times a
hospital stay.
centres unknown)
Exclusion: unclear – abstract only.
Nebulisations given three times a
day, each dose was administered with
day via a nebuliser, albuterol was
Albuterol.
[27]
given with each dose.
Pandit et al 2013 /
Inclusion: 2 to 12 months and admitted with acute
3% Hypertonic saline (HS) (4ml).
0.9% saline (NS) (4ml). The
Length of hospital stay, improvement in
India (Single centre)
bronchiolitis.
The nebulisation was given three
nebulisation was given three times
Respiratory Distress Assessment Instrument
[65]
Exclusion: Previous wheezing and respiratory distress,
times with an interval of one hour,
with an interval of one hour, there
score, haemoglobin saturation, respiratory rate,
family history of asthma, atopy, congenital heart disease,
there after nebulisation was given
after nebulisation was given every 6
heart rate, number of add on treatments and
ventilation as new-born, patients with shock, seizures, heart
every 6 hours until discharge via a
hours until discharge via a nebuliser.
adverse events.
rate (>180/min), respiratory rate (>100/min) and in
nebuliser (flow rate 6-8 L/minute).
Administered with 1ml/1mg
respiratory failure, consolidation lung on X-ray.
Administered with 1ml/1mg
Adrenaline.
Adrenaline.
Sharma et al 2013/
Inclusion: Children from 1- 24 months,1st episode of acute
3% Hypertonic saline (HS) (4ml),
0.9% saline (NS) (4ml), administered
Length of hospital stay, clinical severity scores
India (Number of
bronchiolitis, hospitalised, clinical severity score 3-6.
administered every 4 hours, 6
every 4 hours, 6 times a day till ready
and adverse events.
centres
Exclusions: obtunded consciousness, cardiac disease,
times a day till ready for discharge
for discharge via a nebuliser (flow
unknown)[64]
chronic respiratory disease, previous wheezing episode,
via a nebuliser (flow rate 7
rate 7 L/minute). Administered with
progressive respiratory distress needing respiratory support
L/minute). Administered with 2.5
2.5 mg salbutamol. The nebuliser was
other than oxygen.
mg salbutamol. Nebuliser was
administered until empty.
administered until empty.
Silver et al 2014 /
Inclusion: Patients up to 12 months of age, admitted to
3% Hypertonic Saline (HS) (4ml),
0.9% normal saline (NS) (4ml),
Length of hospital stay, readmission for
New York (Number
hospital with bronchiolitis.
administered every 4 hours until
administered every 4 hours until
bronchiolitis within 30 days of discharge and
of centres unknown)
Exclusion: Status asthmaticus, chronic cardiopulmonary
discharge. Administered using a
discharge via a nebulizer with 5 litres
adverse events.
[70]
disease, Trisomy 21and immunodeficiency or transplant
standard pressurised hospital wall
oxygen flow. Administered until
recipient or neuromuscular disease. Admission directly to
nebuliser flow rate 5L/min and
nebuliser treatment complete.
ICU, previous use of nebulized hypertonic saline less than
administered until nebuliser
12 hours prior to presentation and previous enrolment in the
treatment complete.
study in 72 hours prior to presentation.
Sosa-Bustamante et
Inclusion: Aged 2-24 months, first episode of wheezing
3% Hypertonic Saline (HS) (4ml),
0.9% Hypertonic Saline (NS) (4ml),
Score respiratory distress, hours of hospital
al 2014 / Mexico
associated with respiratory distress, history of upper
nebulized for 3 initial sessions
administered via nebulisations for 3
stay, hospital readmission and frequency of
(Single centre) [26]
respiratory tract infections and evaluation of respiratory
lasting 20 minutes each and every
initial sessions lasting 20 minutes
complications of the disease itself.
difficulty with Scale Hospital Sant Joan de Deu from 6 – 16
4 hours during hospital stay, 100
each and every 4 hours during
at entry points.
micrograms / kg salbutamol was
hospital stay. Administered with 100
Exclusion: Subjects with history of previous wheezing,
given with each dose.
micrograms / kg salbutamol.
asthma, or who have received bronchodilator treatment
before the present illness. Patients with chronic lung
disease, heart disease, with congenital or acquired anatomic
abnormalities of the airway.
Tal et al 2006 / Israel
Inclusion: children under 12 months, clinical presentation of
3% Hypertonic saline (HS) (4ml),
0.9% Saline (NS) (4ml), 3 treatments
Length of hospital stay, change in clinical
(Number of centres
viral bronchiolitis that led to hospitalization.
3 treatments each day
each day administered every 8 hours
severity scores and adverse events.
unknown) [19]
Exclusion: Cardiac disease, chronic respiratory disease,
administered every 8 hours via a
via a nebuliser (output 0.25 ml/min).
previous wheezing episode, age >12 months, 02 sats <85%,
nebuliser (output 0.25 ml/min).
Administered with 1.5mg epinephrine.
obtunded consciousness and/or progressive respiratory
Administered with 1.5mg
The nebuliser was administered until
failure needing ventilation.
epinephrine. Nebuliser
empty.
administered until empty.
Teunissen et al 2014 /
Inclusion: Children aged 0-24 months, admitted to hospital
3% Hypertonic saline (HS) (4ml),
0.9% saline (NS) (4ml), administered
Length of hospital stay, clinical severity scores,
The Netherlands
with viral bronchiolitis with a Wang score of >3.
6% Hypertonic saline (HS) (4ml).
every 8 hours until discharge via a
transfer to Paediatric Intensive Care Units,
(Multi-centre) [69]
Exclusion: Excluded if Wang score improved by at least 2
Administered every 8 hours until
HOT Top Plus Nebuliser (flow rate 6-
need/duration of tube feeding or supplemental
points after inhalation, congenital heart disease, chronic pre-
discharge via a HOT Top Plus
8 L/minute). Administered with 2.5
oxygen and adverse events.
existent lung disease, T-cell immunodeficiency,
Nebuliser (flow rate 6-8
mg salbutamol. The nebuliser was
corticosteroid treatment and previous wheezing, eczema or
L/minute). Administered with
administered until empty.
food allergy.
2.5mg salbutamol. Nebuliser
administered until empty.