Objective: The objective was to determine whether nebulized hypertonic (3%) saline with adrenaline is more effective than nebulized0.9% saline with adrenaline in the treatment of acute bronchiolitis. Materials and Methods: In this randomized, double-blind, controlledstudy 100 patients were randomly allocated into two groups (50 patients in each group). In Group A (normal saline group), 4 ml ofnormal saline (0.9%) and 1 ml of 1:1,000 adrenaline was given as nebulization with oxygen flow of 6-8 L/min. In Group B (hypertonicsaline group), 4 ml of hypertonic saline (3%) and 1 ml of 1:1,000 adrenaline was given as nebulization with oxygen flow of 6-8 L/min.The nebulization was given at an interval of 4 h, 6 times daily till the patient was ready for discharge. Results: The percentageimprovement in clinical severity scores after inhalation therapy was not significant in Group A on 1st-3rd day after admission (3.4%,2.1%, and 4%, respectively). In Group B, significant improvement was observed on these days (7.4%, 8.7%, and 9.9%, respectively,p&lt;0.001). Furthermore, the improvement in clinical severity scores differed significantly on each of these days between the two groups.Using 3% saline decreased the hospitalization stay by 25%, from 3.4±1.7 days in Group A to 2.5±1.4 days in Group B (p&lt;0.05).Conclusion: In the treatment of acute bronchiolitis, 3% saline nebulization with adrenaline decreases the length of hospitalization andsymptoms as compared to 0.9% saline nebulization

Babu, M T Suresh

Kumar, P Sunil

Ragavendra, K

Sreenivasa, B

English

Atharva Scientific Publications (E-Jounals)

Vol 2 | Issue 2 | Apr - Jun 2015 Indian J Child Health 55
Sreenivasa et al. Normal saline versus hypertonic saline in acute bronchiolitis
Original Article
A randomized controlled study of nebulized 3% saline versus 0.9% saline with 
adrenaline in the treatment of acute bronchiolitis
B Sreenivasa1, P Sunil Kumar2, M T Suresh Babu1, K Ragavendra1
From 1Department of Pediatrics, Basaveshwara Medical College and Hospital, Chitradurga - 577 501, Karnataka, India, 2Department 
of Pediatrics, Adichunchanagiri Institute of Medical Science, B.G. Nagara - 571 448, Karnataka, India
Correspondence to: Dr. P Sunil Kumar, S/o B. Puttaswamy Gowda, Behind Guru Theatre, B.M. Road, Hassan - 573 201, Karnataka, 
India. Phone: +91-9902038797, E-mail: drpusuku@gmail.com
Received - 03 March 2015 Initial Review - 09 April 2015 Published Online - 25 May 2015
Abstract
Objective: The objective was to determine whether nebulized hypertonic (3%) saline with adrenaline is more effective than nebulized 
0.9% saline with adrenaline in the treatment of acute bronchiolitis. Materials and Methods: In this randomized, double-blind, controlled 
study 100 patients were randomly allocated into two groups (50 patients in each group). In Group A (normal saline group), 4 ml of 
normal saline (0.9%) and 1 ml of 1:1,000 adrenaline was given as nebulization with oxygen flow of 6-8 L/min. In Group B (hypertonic 
saline group), 4 ml of hypertonic saline (3%) and 1 ml of 1:1,000 adrenaline was given as nebulization with oxygen flow of 6-8 L/min. 
The nebulization was given at an interval of 4 h, 6 times daily till the patient was ready for discharge. Results: The percentage 
improvement in clinical severity scores after inhalation therapy was not significant in Group A on 1st-3rd day after admission (3.4%, 
2.1%, and 4%, respectively). In Group B, significant improvement was observed on these days (7.4%, 8.7%, and 9.9%, respectively, 
p<0.001). Furthermore, the improvement in clinical severity scores differed significantly on each of these days between the two groups. 
Using 3% saline decreased the hospitalization stay by 25%, from 3.4±1.7 days in Group A to 2.5±1.4 days in Group B (p<0.05). 
Conclusion: In the treatment of acute bronchiolitis, 3% saline nebulization with adrenaline decreases the length of hospitalization and 
symptoms as compared to 0.9% saline nebulization.
Key words: Bronchiolitis, Hypertonic saline, Normal saline, Adrenaline
Acute bronchiolitis is the most frequent lower respiratory infection requiring hospitalization in infants [1-3]. Peribronchial inflammation, airway edema, mucus 
plugging and necrosis, and desquamation of ciliated epithelial 
cells are the predominant pathological processes implicated in 
acute bronchiolitis [4]. Theoretically, any therapeutic modality 
which can improve clearance of airway secretions and minimize 
edema should be beneficial. Four such modalities that have been 
studied targeting the above are inhaled epinephrine, recombinant 
deoxyribonuclease, chest physiotherapy, and hypertonic saline [5].
Of these, hypertonic saline has recently shown some 
promising results, the basic premise for its use stemming from 
extrapolation of its benefits seen in asthma, bronchiectasis, 
cystic fibrosis, and sinonasal diseases [4]. It has been postulated 
that saline hydrates airway surface liquid, improves impaired 
mucociliary clearance and aids water absorption from the 
mucosa, thereby reducing airway edema [5]. This modality 
has enormous potential for cost-saving, both in developing 
and developed countries, more so if it could actually reduce 
the length of hospitalization as suggested by a recent Cochrane 
review [6].
We conducted this study to evaluate the efficacy of 
nebulized hypertonic (3%) saline in children diagnosed 
with clinical bronchiolitis. Limited number of studies has 
been published from India and abroad regarding the use of 
hypertonic saline with adrenaline nebulization in bronchiolitis 
in children.
MATERIALS AND METHODS
The present study was a randomized double-blind, controlled 
trial conducted at a tertiary care teaching institution of 
Karnataka during the period from March 2013 to January 2015. 
Children 1-24 months of age with a clinical diagnosis of acute 
bronchiolitis were enrolled. Bronchiolitis was defined by the first 
episode of wheezing along with prodrome of upper respiratory 
tract infection including rhinorrhea, cough, and sometimes 
low-grade fever. Children with obtunded consciousness, 
cardiac disease, chronic respiratory disease, previous wheezing 
episode, progressive respiratory distress requiring respiratory 
support other than supplemental oxygen, and those having 
received nebulized hypertonic saline or adrenaline within the 
previous 12 h were excluded from the study. The Institutional 
Vol 2 | Issue 2 | Apr - Jun 2015 Indian J Child Health 56
Sreenivasa et al. Normal saline versus hypertonic saline in acute bronchiolitis
Ethical Committee of our hospital approved the study. Signed 
informed consent was obtained from the parents of all children.
Sample size was calculated using Epi-info 06 software 
and sample of 100 was selected to provide 80% power and a 
confidence interval of 95%. Recruited children were randomly 
allocated into two groups (50 patients in each group) using a 
computer-generated random number table. In Group A (normal 
saline group), 4 ml of normal saline (0.9%) and 1 ml of 1:1,000 
adrenaline was given as nebulization with oxygen flow of 
6-8 L/min. In Group B (hypertonic saline group), 4 ml of 3% 
saline and 1 ml of 1:1,000 adrenaline was given as nebulization 
with oxygen flow of 6-8 L/min [4]. The nebulization was given 
at intervals of 4 h, 6 times daily till the patient was ready for 
discharge. Antibiotics were used in the presence of fever, high 
white blood cell count, infiltration on chest X-ray.
The following parameters (Table 1) were measured and 
recorded at admission using a clinical severity score described 
by Wang et al. along with pulse rate and oxygen saturation [7]. 
Patients were monitored for improvement or worsening of 
the condition using above-mentioned parameters at 12 h 
intervals until they were ready for discharge. Discharge criteria 
included feeding well orally, no need for intravenous fluids 
and supplemental oxygen, clinical severity score <3, absence 
of accessory muscle use or tachypnea (respiratory rate 
<31 breaths/min), and oxygen saturation >92% on room air.
Outcome Measures
Primary outcome: Length of hospital stay; secondary outcome: 
Improvement in clinical severity score, oxygen saturation, 
pulse rate, number of add-on treatment.
Statistical Analysis
All continuous variables were examined using the paired or 
unpaired t-test as appropriate. Non-continuous variables were 
examined using χ2 test. The mean ± standard deviation (with 
95% confidence interval) expresses the central tendency of 
the data. To examine the change in clinical severity score 
after nebulizer, paired t-test was carried out in each treatment 
groups separately. For the analysis, p<0.05 was considered 
significant.
RESULTS
Total 100 patients were included in the study with 50 cases in 
each group (Fig. 1). Two study groups were similar in baseline 
characteristics (Table 2) including age, sex, and clinical severity 
score.
Primary Outcome
The mean hospitalization stay was 2.9±1.6 days for the entire 
study group. This parameter differed significantly between 
two groups, being 3.4±1.7 days for Group A and 2.5±1.4 for 
Group B (p<0.05).
Secondary Outcome
The percentage fall of clinical severity score after inhalation 
therapy was not significant in Group A on first, second, and 
3rd day after hospitalization (3.4%, 2.1%, and 4%, respectively). 
In Group B, significant differences were observed on each of 
the first 3 days (7.4%, 8.7%, and 9.9%, respectively, p<0.001). 
Furthermore, fall in clinical scores differed significantly 
between the two groups on each of these days. In first 3 days, 
there was a trend for more add-on inhalation therapy needed 
per day for Group A (1.1±0.9) as compared to Group B 
(0.9±0.7). However, it was statistically not significant (p=0.1). 
No adverse effects were observed in patients in either of the 
groups and no significant difference was seen in pulse rate and 
oxygen saturation at any time between two groups.
In Group A (0.9% saline group), 22 children received 
antibiotics, 5 received steroid (injectable or oral). Similarly 
in Group B (hypertonic saline group), 23 received antibiotics, 
6 received steroid (injectable or oral). These extra additions did 
not have any impact on the intervention outcome, as they were 
all statistically not significant.
DISCUSSION
Our study shows that by substituting normal saline solution 
with hypertonic saline in the inhalation mixture for delivering 
adrenaline to hospitalized infants with viral bronchiolitis, the 
hospital stay was reduced by 25%, from 3.4 days in the 0.9% 
saline solution group (Group A) to 2.5 days in the 3% saline 
Table 1: Clinical severity score
Variables 0 1 2 3
Respiratory rate/min
<1-year <50 50-60 60-70 >70
>1-year <30 31-45 46-60 >60
Wheezing None Terminal expiratory or 
only with stethoscope
Entire expiration or audible on 
expiration without stethoscope
Inspiration and expiration 
without stethoscope
Retraction None Intercostal only Tracheosternal Severe with nasal flaring
General condition Normal Irritable, lethargic, poor feeding
Vol 2 | Issue 2 | Apr - Jun 2015 Indian J Child Health 57
Sreenivasa et al. Normal saline versus hypertonic saline in acute bronchiolitis
solution group (Group B). This possible effect could bear an 
important economic and clinical impact worldwide especially 
in developing countries. This study demonstrated a significantly 
better improvement in clinical severity score after adrenaline 
inhalation in hypertonic (3%) saline solution as compared to 
adrenaline in 0.9% saline solution.
Studies conducted by Grewal et al. [8], Anil et al. [9] and 
Sarrell et al. [10] did not show any significant advantage of 
hypertonic saline over normal saline in terms of improvement in 
clinical severity scores or hospitalization rates. This can be due 
to their small sample size and enrollment of cases admitted in 
emergency care settings. Our study was in line with the studies 
by Kuzik et al. [11], Mandelberg et al. [12], Luo et al. [13] 
and Tal et al. [14] which showed significant difference in terms 
of hospital stay and clinical severity scores between normal 
saline and hypertonic saline groups. This may be due to the 
enrollment of mild to moderately severe cases of bronchiolitis 
conducted in hospitalized patients.
Bronchiolitis is an infectious inflammation of respiratory 
mucosal epithelium, pronounced in small bronchioles. This 
leads to tissue edema and mucus production, resulting in 
thick mucus plaques within the airway lumen, and increase in 
intraluminal deoxyribonucleic acid (DNA) concentration [15]. 
DNA is released due to lysis of inflammatory and sloughed 
respiratory epithelial cells which further increases the viscosity 
and adhesiveness of lung secretions. In our study, possible 
mechanism can be an improvement in mucociliary transport 
and better elimination of intracellular debris leading to reduced 
viral load and milder ongoing inflammation within the airways. 
This might decrease an opportunity for secondary bacterial 
overgrowth and thereby may contribute to the favorable effect 
of decreasing the post-inhalation therapy clinical severity score.
The strength of this study was its randomized control 
design using standard protocol with a good match of 
baseline characteristics such as clinical presentation, signs on 
examination, and laboratory findings between 2 groups. Our 
study evaluated efficacy in non-critically sick admitted patients 
with acute bronchiolitis. Furthermore, there were no dropouts 
or withdrawal of patients during the study period in either 
group which strengthen confidence in the outcome. We used a 
lower concentration of hypertonic saline (i.e., 3%) in order to 
decrease the possible negative effect of higher concentrations 
(>7% saline) on ciliary beat frequency and to decrease the risk 
of bronchospasm. In addition, by giving hypertonic saline with 
adrenaline, a bronchodilator, any additional bronchoconstriction 
effect secondary to hypertonic saline was avoided.
Limitations of this study were patients enrolled based on 
clinical diagnosis and not confirmed by virological studies, 
the exact duration of hypertonic saline effect (half-life) and, 
therefore, its continuing impact on clinical parameter is not 
known and should be investigated further. More research with 
higher saline concentrations and more frequent inhalation of 
hypertonic saline is warranted to further clarify this potential 
treatment modality. This treatment has an excellent safety 
profile.
CONCLUSION
In the treatment of acute bronchiolitis, 3% saline nebulization 
with adrenaline significantly decreases the length of hospital 
stay and percentage fall of the clinical severity score as 
compared to 0.9% saline nebulization.
REFERENCES
1. Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, 
Sterling L, et al. Diagnosis and testing in bronchiolitis: A systematic 
100 patients met inclusion criteria
No patients refused enrollment and no dropouts  
100 patients randomized
Group A (50 patients) – 0.9% saline group Group B (50 patients) – 3% saline group
50 analyzed 50 analyzed
Figure 1: Participants flow diagram
Table 2: Baseline characteristics of study subjects
Characteristics 0.9% saline 
Group, n=50
3% saline 
Group, n=50
p value
Age in months 5.5±3.9 4.4±3.4 NS
Male/female 28/22 26/24 NS
Baseline severity score 8.0±1.3 8.18±1.4 NS
Baseline oxygen 
saturation %
92.8±2.8 91.9±2.6 NS
NS: Not significant
Vol 2 | Issue 2 | Apr - Jun 2015 Indian J Child Health 58
Sreenivasa et al. Normal saline versus hypertonic saline in acute bronchiolitis
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Funding: None; Conflict of Interest: None Stated
How to cite this article: Sreenivasa B, Kumar PS, Babu MT, 
Ragavendra K. A randomized controlled study of nebulized 3% 
saline versus 0.9% saline with adrenaline in the treatment of acute 
bronchiolitis. Indian J Child Health. 2015;2(2):55-58.


A randomized controlled study of nebulized 3% saline versus 0.9% saline with adrenaline in the treatment of acute bronchiolitis

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A randomized controlled study of nebulized 3% saline versus 0.9% saline with adrenaline in the treatment of acute bronchiolitis

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