Acute bronchiolitis is an
important cause of morbidity in infants and
children. It is the most common cause of
hospitalization due to acute lower respiratory
tract infection (LRTI) in infants. A number of
definitions have been proposed for bronchiolitis:
The American Academy of Pediatrics (AAP) defines
bronchiolitis as ‘acute inflammation, edema and
necrosis of epithelial cells lining small
airways, increased mucus production, and
bronchospasm’ [1]; but this definition is of
little clinical significance. Another useful
definition, which has been used in many clinical
studies, is: the first episode of wheezing in a
child younger than 12 to 24 months who has
physical findings of a viral respiratory
infection and has no other explanation for the
wheezing, such as pneumonia or atopy [2].
Methods
A search of articles
published on bronchiolitis was performed using
PubMed. The areas of focus were diagnosis,
treatment and prevention of bronchiolitis in
children. Relevant information was extracted
from English language studies published over the
last 20 years. In addition, the Cochrane
Database of Systematic Reviews was searched. We
selected relevant articles/studies/guidelines in
various domains for inclusion in this review.
Etiology
Bronchiolitis is typically
caused by a viral infection. With improvement in
diagnostic ability to identify viruses in
respiratory secretions (nasopharyngeal
aspirates) multiple viral agents have been
identified as causative agents of acute
bronchiolitis: Respiratory syncytial virus
(RSV), Rhinovirus, Parainfluenza viruses,
Influenza virus, Adenovirus, and Coronavirus.
RSV is the most common cause, accounting for
50-80% cases [3]. In Indian studies, RSV
infection was diagnosed in 30-70% of children
with bronchiolitis [4-6]. The proportion of
disease caused by specific viruses varies
depending upon the season and the year, and
there is a wide variation in the reported
proportions among various studies. Most of the
studies implicate rhinovirus (which normally
causes common cold) as the second most common
cause of bronchiolitis. Molecular diagnostic
techniques have also revealed a high frequency
(15-25%) of mixed viral infections among
children evaluated for bronchiolitis [7-11].
Apart from the above
mentioned viruses, newer respiratory viruses
have been described in children, including human
metapneumovirus (hMPV) and human bocavirus (HBoV)
[12]. Some of the recent studies have found hMPV
as a common cause of respiratory tract
infections in children throughout the world [13]
and often second only to RSV as a cause of
bronchiolitis in infants. In contrast to hMPV,
the role of HBoV in causing respiratory
illnesses is less clear. This is because HBoV is
associated with high coinfection rate (50-60%),
and therefore the role that HBoV alone plays in
illness can be questioned. Another problem with
HBoV is its lack of cultivability and hence lack
of appropriate models for pathogenesis [12].
Epidemiology
Bronchiolitis typically
affects children younger than two years with a
peak incidence between two and six months of
age. In a prospective hospital-based study from
Southern India, of 114 children with
bronchiolitis, 87 (76%) were less than 1 year
and 107 (94%) were less than 2 years of age
[14]. Bronchiolitis occurs in epidemics during
winter months. In India, outbreaks occur from
September to March.
Clinical Presentation
Children with bronchiolitis
typically present with a viral upper respiratory
prodrome comprising of rhinorrhea, cough, and on
occasion, a low grade fever. The onset of these
symptoms is acute. Within 1-2 days of these
prodromal symptoms, the cough worsens and child
may also develop rapid respiration, chest
retractions, and wheezing. The infant may show
irritability, poor feeding, and vomiting.
Though, in majority of cases, the disease
remains mild and recovery starts in 3-5 days,
some of these children may continue to worsen.
The importance of a detailed
clinical assessment of these children cannot be
overemphasized. The components of this
assessment include, in-depth review of the
child’s symptoms, impact of these symptoms on
his feeding (respiratory distress often prevents
adequate oral fluid intake and causes
dehydration), assessment of the child’s
responsiveness and alertness, identification of
various co-morbidities like underlying chronic
lung disease, congenital heart disease or immuno-compromised
state, and complete physical examination. Most
of the children with bronchiolitis have
tachycardia and tachypnea. Pulse oximetry helps
us in deciding about the need for supplemental
oxygen. The chest may appear hyper-expanded and
may be hyperresonant to percussion. Wheezes and
fine crackles may be heard throughout the lungs.
Severely affected patients have grunting, marked
retractions. They may be cyanosed, and may have
impaired perfusion. Apnea may occur in those
born prematurely and in younger than two months
of age (15). Other associated problems that may
occur in children with bronchiolitis include
conjunctivitis, otitis media and pharyngitis.
Disease Course and Prediction
of Severity
Bronchiolitis usually is a
self-limited disease. Although symptoms may
persist for several weeks, the majority of
children who do not require hospital admission
may continue to have low grade symptoms upto 4
weeks [16]. In previously healthy infants, the
average length of hospitalization is three to
four days [17]. The course may be prolonged in
younger infants and those with co-morbid
conditions (e.g., chronic lung disease).
A number of risk factors and
clinical findings have been proposed to predict
the severity of disease in children with
bronchiolitis (Table I). Various
studies and treatment trials have also used
clinical scores (e.g., the Respiratory
Distress Assessment Instrument) to predict the
disease severity in children with bronchiolitis,
but none of these scores have been validated for
clinical predictive value in bronchiolitis. It
should be emphasized that repeated observation
over a period of time may provide a more valid
overall assessment of the disease severity than
a single examination [1]. Risk factors for
mortality include: younger age (<6 months),
prematurity, underlying chronic lung disease,
cyanotic heart disease or immunocompromised
state [24].
TABLE I Predictors of Severe Bronchiolitis
A. |
Host Related Risk Factors [18-20] |
• |
Prematurity |
• |
Low birth weight |
• |
Age less than 6 to 12 weeks |
• |
Chronic pulmonary disease |
• |
Hemodynamically significant congenital
heart disease (eg, moderate to severe
pulmonary hypertension, cyanotic heart
disease, or congenital heart disease
that requires medication to control
heart failure) |
• |
Immunodeficiency |
B. |
Environmental Risk Factors [21] |
• |
Having older siblings |
• |
Passive smoke |
• |
Household crowding |
• |
Child care attendance |
C. |
Clinical Predictors [18,22,23] |
• |
Toxic or ill appearance |
• |
Oxygen saturation <95 percent by pulse
oximetry while breathing room air |
• |
Respiratory rate ³70 breaths per minute |
• |
Moderate/Severe chest retractions |
• |
Atelectasis on chest radiograph |
Baseline Work-up
The diagnosis of
bronchiolitis and the assessment of disease
severity should be based on history and physical
examination. Laboratory tests and radiographs
are not required and do not alter treatment
decisions [1].
Radiographs
The radiographic
abnormalities of bronchiolitis are variable and
include hyperinflation and peribronchial
thickening. Patchy atelectasis may result from
airway narrowing and mucus plugging. In a
prospective study involving 265 children (age
2-23 months) with bronchiolitis, routine
radiography identified findings inconsistent
with bronchiolitis in only 2 cases, and in
neither case did these findings affect the acute
management. In fact, radiographic review
promoted unnecessary use of antibiotics [25].
Results of this study highlight that radiographs
do not change the management of acute
bronchiolitis. A chest X-ray may be obtained if
the diagnosis is in doubt, co-morbidity like
chronic lung disease or heart disease is
suspected, there is no improvement or if the
child is severely ill [1].
Laboratory tests
Laboratory tests are not
routinely indicated in the evaluation of infants
and young children with suspected bronchiolitis.
Abnormalities in total and differential white
blood cell counts do not predict serious
bacterial infection in infants and young
children hospitalized with lower respiratory
tract infection due to RSV [26].
Measurement of lactate
dehydrogenase (LDH) concentration in the
nasal-wash fluid has been proposed as an
objective indicator of bronchiolitis severity;
increased values (suggestive of a robust
antiviral response) have been shown to be
associated with decreased risk of
hospitalization [27]. This observation needs
further validation before nasal wash LDH
measurement is used to make decisions regarding
hospitalization for children with bronchiolitis.
Virologic testing
Clinical course, treatment
and outcome of acute bronchiolitis due different
viral infections are similar; therefore,
identification of viral agents does not affect
management in the majority of patients. However,
in the hospital setting, determining the
responsible virus may help to avoid unnecessary
antibiotic use and also prevent nosocomial
transmission to other patients.
The available tools for
etiologic diagnosis include Antigen detection,
Immunofluorescence, Polymerase Chain Reaction
(PCR), and culture of respiratory secretions
obtained by nasal wash or nasal aspirate. New
techniques such as real-time polymerase chain
reaction (PCR), nested PCR, and multiplex PCR
have improved the virologic diagnosis of
bronchiolitis immensely [5,28, 29]. In a study
to detect RSV in children <2 years with acute
respiratory tract illness using three different
techniques: viral culture, direct
immunofluorescence, and nested PCR, it was found
that PCR was the most sensitive technique (11.1%
positivity), followed by direct
immunofluorescence (7.9% positivity) and viral
culture (6.3% positivity) [30].
Therapy
Acute bronchiolitis is, in
the majority of cases, a mild and self-limiting
illness that can be managed on ambulatory basis
with supportive care alone. Management mainly
consists of educating parents or caregivers
about adequate feeding and to report any
deterioration (such as increasing difficulty in
breathing, chest indrawing or problems with
feeding) to an appropriate health care facility.
Multiple intervention studies have been carried
out to improve treatment of bronchiolitis. Still
there is much controversy, confusion, and lack
of evidence over the best treatment for infants
hospitalised with moderate to severe
bronchiolitis [31] (Table II).
TABLE II Summary of Interventions Used For Management of Acute Bronchiolitis
Interventions with clear evidence of
effectiveness
• Supportive care
(supplemental oxygen, IV fluids)
Interventions which are possibly
effective
• Nebulized
bronchodilators (epinephrine/salbutamol)
• Nebulized Hypertonic
saline
• Dexamethasone +
Inhaled epinephrine
Interventions which are possibly
effective for most severe cases
• CPAP
• Surfactant
• Heliox
• Aerosolized
Ribavirin
Interventions which are possibly
ineffective
• Oral bronchodilators
• Montelukast
• Inhaled/Systemic
corticosteroids
• Chest physiotherapy
• Antibiotics
• Steam inhalation
• RSV polyclonal
immunoglobulin / Palivizumab
• Inhaled Furosemide/Inhaled
interferon alfa-2a / Inhaled recombinant
human DNase |
Supportive Care
Supportive care remains the
cornerstone of treatment of children with
bronchiolitis. It includes maintenance of
adequate hydration, provision of respiratory
support as necessary, and monitoring for disease
progression.
A. Fluid administration
Children with bronchiolitis
are at an increased risk of dehydration because
of their increased needs (related to fever and
tachypnea) and reduced oral acceptance.
Clinicians should carefully assess hydration and
ability to take fluids orally. Children having
dehydration or difficulty in feeding safely
because of respiratory distress should be given
intravenous fluids [1]. For children who can
tolerate enteral feedings, small frequent
feedings or orogastric or nasogastric feedings
may be used to prevent dehydration. Children
with bronchiolitis are also at an increased risk
of fluid retention (and subsequent pulmonary
congestion) due to excessive antidiuretic
hormone production, so urine output should be
carefully monitored [1,32].
B. Nasal Decongestion
Saline nose drops and
cleaning of nostrils by gentle suction may help
to relieve nasal block. Instilling saline drops
and cleaning nostrils by gentle suction before
feeding may be helpful. Parents should be
educated about instilling saline drops and
cleaning secretions from nose before discharge
from hospital [33].
C. Respiratory support
Supplemental oxygen
The major consequence of
airway obstruction and concomitant poor
distribution of ventilation and perfusion in
bronchiolitis is hypoxemia. Humidified oxygen
should be administered to hypoxemic infants by
any technique familiar to the nursing personnel
(nasal cannula, face mask, or head box). Pulse
oximetry is the most commonly used tool to
decide about oxygen supplementation. The cut-off
level of oxyhemoglobin saturation (SpO
and respiratory distress in bronchiolitis was of
low methodological quality, and there was no
conclusive evidence that CPAP reduced the need
for intubation [36]. However, a recent
randomised trial comparing nasal CPAP and oxygen
inhalation concluded that CPAP resulted in rapid
reduction in work of breathing and improvement
in the respiratory distress score at 6 hour. The
improvement was proportional to the initial
severity, suggesting that, early use of CPAP in
severe forms of the disease may be beneficial
[38]. CPAP level of 7 cm of water was associated
with greatest improvement [39]. Current evidence
is inconclusive regarding routine use of CPAP in
children with acute bronchiolitis. More studies
with adequate numbers and better quality are
required.
Mechanical Ventilation
The major indications for
intubation and mechanical ventilation are
clinical deterioration (worsening respiratory
distress, listlessness, and poor peripheral
perfusion), apnea and/or bradycardia, and
hypercarbia. Infants do not usually require
intubation for oxygenation alone. In a
prospective cohort study done in children
admitted with RSV LRTI, approximately 9% of
patients required mechanical ventilation [19].
The median duration of mechanical ventilation is
relatively short, about 5 days, but protracted
courses of ventilation may be required [40].
Chest Physiotherapy
Chest physiotherapy clears
the excessive respiratory secretions, and thus
helps to reduce airway resistance, the work of
breathing, and enhances gas exchange. Inspite of
this theoretical advantage, a systematic review
of nine randomized trials concluded that chest
physiotherapy using vibration and percussion or
passive expiratory techniques did not improve
respiratory parameters, reduce supplemental
oxygen requirement, or reduce length of hospital
stay [41]. The use of chest physiotherapy is
discouraged in children with bronchiolitis,
because it may increase the distress and
irritability of ill infants.
Bronchodilators
Routine use of
bronchodilators in the management of
bronchiolitis is debatable. One of the major
problems with interventional trials evaluating
bronchodilators in infants and children with
bronchiolitis is the difficulty in
distinguishing bronchiolitis from virus-induced
wheezing and asthma. Children in the latter
categories, who often respond to bronchodilators
(and gluco-corticoids), are invariably included
in bronchiolitis trials, making it difficult to
determine the effects of these medications in
children with true viral bronchiolitis.
In a meta-analysis of 28
trials (1912 participants) comparing
bronchodilators other than epinephrine (included
salbutamol, terbutaline, ipratopium) with
placebo, there were no significant differences
in improvement in oxygenation, hospitalization
rate, or duration of hospitalization. A modest
improvement in clinical scores was noted in the
treated outpatients; however, this small
improvement in clinical scores must be weighed
against the costs and adverse effects of
bronchodilators [42].
Another meta-analysis of 19
trials (2256 participants) compared nebulized epinephrine with
placebo or other bronchodilators [43].
Epinephrine versus placebo among outpatients
showed a significant reduction in admissions at
Day 1 but not at Day 7 post-emergency department
visit. Epinephrine versus salbutamol
showed no differences among outpatients for
admissions at Day 1 or 7. Although epinephrine
was associated with decreased length of stay
compared with salbutamol, epinephrine did not
decrease length of stay when compared with
placebo. This review demonstrated the
superiority of epinephrine compared to placebo
for short-term outcomes for outpatients,
particularly in the first 24 hours of care, but
there was no evidence to support the use of
epinephrine for inpatients.
Oral bronchodilators should
not be used in the management of bronchiolitis.
They neither shorten clinical illness nor
improve clinical parameters, but are associated
with adverse effects (increased heart rate)
[44].
Based on the current evidence
it is not easy to decide about bronchodilator
uses. It is also difficult to distinguish
bronchiolitis from viral infection associated
wheezing or multi-trigger wheeze. In the latter
condition, broncho-dilators may improve clinical
outcome. Therefore, we consider a trial of
bronchodilator with careful monitoring. Choice
of bronchodilator may be based on personal or
family history of atopy or asthma; if present,
salbutamol inhalation may be given. In absence
of it, a trial of epinephrine inhalation may be
given. Further doses of either medications may
be continued only on documentation of
improvement.
Steroids
Systemic corticosteroids
Initial studies of the
treatment of bronchiolitis with corticosteroids
suggested that steroids might favourably
influence mortality and morbidity. However,
large controlled studies have failed to
demonstrate any significant clinical effect. A
meta-analysis evaluating the use of systemic
glucocorticoids (oral, intramuscular, or
intravenous) and inhaled glucocorticoids for
acute bronchiolitis in children (0 to 24 months
of age) included 17 trials with 2596 patients
[45]. In pooled analyses, no significant
differences were found in hospital admission
rate, length of stay, clinical score after 12
hours, or hospital readmission rate. Hence, it
is recommended not to use glucocorticoids in
healthy infants and young children with a first
episode of bronchiolitis. Another meta-analysis
(of 3 studies) studied the role of systemic
steroids in critically ill children with
bronchiolitis [46]. It was found that systemic
corticosteroid showed no overall effect on
duration of mechanical ventilation.
Corticosteroids plus
Epinephrine
A possibility of synergy
between epinephrine and glucocorticoids has also
been evaluated. There is one trial which
suggested that administration of epinephrine and
glucocorticoids in the outpatient setting
prevents hospitalization within seven days [47].
In this multicentre trial, there was a reduction
in hospitalization rates in the group that
received dexamethasone and 2 doses of
epinephrine by nebulizer as compared with those
who were treated with placebo (17.1% vs
26.4%). Number needed to prevent one admission
was 11. However, the strength of evidence was
low and after adjustment for multiple
comparisons, the difference did not reach
statistical significance. This may have a
potential role in future treatment algorithms.
Till additional studies shows similar results
and safety is established, this combination
therapy may be considered under evaluation.
Inhaled Corticosteroids (ICS)
Use of ICS during acute
bronchiolitis has been proposed to prevent post-bronchiolitic
wheezing. A systematic review of 5 studies
involving 374 infants did not demonstrate an
effect of ICS, given during the acute phase of
bronchiolitis, in the prevention of recurrent
wheezing following bronchiolitis [48]. An
additional RCT involving 243 infants with
RSV-related LRTI did not find any effect of
inhaled corticosteroids on recurrent wheeze
[49]. Hence, there is no evidence for use of
inhaled corticosteroids to prevent or reduce
post- bronchiolitis wheezing after RSV
bronchiolitis.
Antibiotics
Unnecessary use of
antibiotics is associated with increased cost of
treatment, adverse reactions and development of
bacterial resistance in community/ geographic
region. In children with bronchiolitis and
fever, the risk of secondary bacterial infection
is low, therefore, routine use of antibiotics is
not recommended. It is recommended that
antibiotics should be used only in children
having specific indications of coexistence of a
bacterial infection [1]. Presence of infiltrates
or alelectasis on X-ray film may not
indicate bacterial infection. Clinical setting,
with consolidation on X-ray film may
indicate a possibility of bacterial pneumonia in
infants with bronchiolitis [50].
A systematic review including
five studies (543 participants) did not find
significant benefits for use of antibiotics in
acute bronchiolitis. However, the review
indicated a need for research to identify a
subgroup of patients who may benefit from
antibiotics [51]. One small study (21
participants) which was included in this review,
compared clarithromycin for 3 weeks with placebo
in children with RSV bronchiolitis. Treatment
with clarithromycin was associated with
reduction in the length of hospital stay,
duration of need for oxygen, and readmission
rates. Clarithromycin was proposed to have a
possible immunomodulatory effect. More
well-planned studies to clarify role of
macrolides in acute bronchiolitis are required
[52].
Hypertonic Saline
Aerosolized hypertonic saline
has been proposed as a therapeutic modality for
acute bronchiolitis. Hypertonic saline may
reverse some pathophysiological abnormalities in
acute bronchiolitis by decreasing epithelial
edema, improving elasticity and viscosity of
mucus and thus improving airway clearance. A
Cochrane review of seven trials involving 581
infants (282 inpatients, 65 outpatients and 234
emergency department patients) with acute
bronchiolitis found that nebulisation with 3%
saline results in a significantly shorter length
of hospital stay as well as a lower clinical
score as compared to nebulisation with 0.9%
saline [53]. The potential side effects,
principally acute bronchospasm, remain a concern
with nebulized hypertonic saline. In six of the
seven trials included in the above mentioned
review, patients received hypertonic saline
inhalation in conjunction with bronchodilators
and no significant adverse events related to 3%
saline inhalation were reported [54].
A recent randomized
controlled trial reported that high volume
normal saline was as effective as 3% saline in
children with mild bronchiolitis. It may be
inferred that improved clearance of mucus in
airway may be function of total mass of NaCl
rather than concentration of NaCl [55].
Hypertonic saline inhalation may be considered
as potential treatment for bronchiolitis.
However, there are several unanswered questions
related to its use including optimal volume,
concentration of saline, frequency of
administration and effective device. Its use
cannot be recommended till all these are
addressed by further studies.
Inhaled Furosemide
Furosemide inhalation in
acute bronchiolitis has been proposed with a
hypothesis that it may improve outcome by acting
on airway smooth muscle, airway vessels,
electrolytes and fluid transport across
respiratory mucosa, and reducing airway
inflammation. One RCT (32 participants) studied
the effect of inhaled furosemide in hospitalized
infants with bronchiolitis, and recorded no
significant clinical effects in these infants
[56]. Therefore, there is no evidence for use of
inhaled furosemide in the management of
bronchiolitis.
Steam inhalation
Steam inhalation/ mist
inhalation has been proposed to improve airway
clearance of mucus and outcome of acute
bronchiolitis. Being less expensive and easily
available, steam was considered to be a suitable
intervention in low income countries. A
systematic review could identify only one RCT
(156 participants) that compared role of
nebulised salbutamol, nebulised saline and mist
in a tent in children with acute bronchiolitis.
[57,58]. Group of children receiving salbutamol
inhalation showed significant improvement in
respiratory distress symptom (RDS) score but
there was no improvement in children receiving
mist in a tent or nebulised saline. In view of
limited experience with mist/ steam inhalation,
more studies are required to prove or disapprove
role of steam inhalation in acute bronchiolitis.
Leukotriene receptor antagonists (Montelukast)
Clinical symptoms and post-bronchiolitis
cough and wheeze are attributed to the increased
cysteinyl leukotrienes in airway secretions of
children with bronchiolitis during acute phase
as well as in short term follow up. Randomized
trials of montelukast as a treatment for acute
bronchiolitis have had conflicting results
[59,60]. Randomized trials of montelukast for
the prevention of airway reactivity and post-bronchiolitis
respiratory symptoms have also had inconsistent
results [61,62]. However, in the largest trial
(979 participants), use of montelukast for 24
weeks was not associated with improvement in
post-bronchiolitis respiratory symptoms [62]. In
view of these studies, montelukast is currently
not recommended for treatment of bronchiolitis
or for prevention of airway reactivity after
bronchiolitis.
Heliox
Heliox (mixture of helium and
oxygen) may improve alveolar ventilation as it
flows through airways with less turbulence and
resistance. This may reduce work of breathing
and improve oxygenation in respiratory illness
with moderate to severe airway obstruction
including acute bronchiolitis. A meta-analysis
of four clinical trials (84 participants), using
heliox demonstrated improved respiratory
distress scores in first hour in children with
moderate to severe acute bronchiolitis. However,
heliox inhalation did not affect need for
intubation and mechanical ventilation and length
of stay in pediatric intensive care unit. There
was significant heterogeneity in the included
studies [63].
It is concluded that evidence
for beneficial role of Heliox in acute
bronchiolitis are inadequate and more experience
is required [64].
Antivirals
Ribavirin, a synthetic
nucleoside analog resembling guanosine, acts by
inhibiting viral protein synthesis, and has a
broad antiviral effect. It is delivered as a
small-particle aerosol for 18 to 20 hours per
day. The drug is relatively expensive and may
lead to some risk (teratogenic effect) to health
care personnel administering the drug [1]. A
systematic review of 10 RCTs (320 participants)
reported no improvement in clinical outcome of
acute bronchiolitis after ribavirin use [65].
Ribavirin may be considered in high risk infants
(immunocompromised and/or hemodynamically
significant cardiopulmonary disease) and in
infants requiring mechanical ventilation [1,
46].
Apart from ribavarin, no
other antiviral is currently approved for use in
bronchiolitis. Numerous other drugs are
undergoing trials for use against RSV, which is
the most common cause of bronchiolitis. The
immuno-suppressive agent leflunomide has been
shown to exert potent antiviral and
anti-inflammatory activity against RSV in
experimental animal models [66]. Another
promising group of drugs currently under
investigation are the small molecule fusion
inhibitors (TMC353121, CL387626, RFI-641,
JNJ-2408068 etc) that inhibit viral fusion by
interacting with the RSV F protein (RSV F
protein mediates the fusion of viral envelope
with host cell membrane) [67,68]. Fusion
inhibitors have also been shown to be effective
against hMPV in experimental animals, and some
researchers have suggested a possibility for use
of these fusion inhibitors for early treatment
in an epidemic context. However, more studies
are needed to characterize the best delivery
mode, dosage, and schedule of administration for
these fusion inhibitors [69].
Surfactant
In severe bronchiolitis there
may be secondary surfactant insufficiency
suggesting possible role of administration of
exogenous surfactant [64]. A meta-analysis
(included three RCTs with total 79 participants)
evaluated the effect of exogenous surfactant in
infants and children with bronchiolitis
requiring mechanical ventilation [70]. The
duration of mechanical ventilation and duration
of ICU stay were significantly lower in the
surfactant group compared to the control group.
Use of surfactant had favourable effects on
oxygenation and CO
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