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Hypertonic Saline for Acute Bronchiolitis

Nebulized Hypertonic Saline for Acute Bronchiolitis in the Emergency Department

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01247064
Enrollment
62
Registered
2010-11-24
Start date
2010-10-31
Completion date
2011-12-31
Last updated
2014-08-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bronchiolitis, Viral, Saline Solution, Hypertonic

Keywords

Bronchiolitis, Hypertonic Saline

Brief summary

The purpose of this study is to determine whether nebulized 3% hypertonic saline (HS) improves respiratory distress in children 2-23 months presenting to the emergency department (ED) with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.

Detailed description

Acute bronchiolitis is the most frequent cause of infant hospitalization in the United States. Bronchiolitis typically refers to a viral lower respiratory tract infection during the first two years of life manifesting as a constellation of clinical symptoms including wheezing, cough and respiratory distress. In addition to a tremendous disease burden, bronchiolitis admissions in the United States cost more than $500 million each year. The primary pathophysiologic processes in bronchiolitis include airway wall and peribronchial inflammation, increased mucous production, sloughing of necrotic epithelial cells, and impaired airway clearance. These processes result in airway obstruction, gas trapping, atelectasis and impaired gas exchange. Standard therapies for bronchiolitis remain supportive, including maintaining hydration and nutrition, ensuring adequate oxygenation, and physical suctioning of the nasal airways to clear secretions. Therapies such as the bronchodilator albuterol, although commonly used in standard practice, have not been proven to impact progression of disease or improve long-term outcomes of bronchiolitis. Nebulized hypertonic saline (HS) has been shown to increase mucociliary clearance in the airways of individuals with healthy lungs. In addition nebulized HS increases airway clearance for disease processes including asthma, cystic fibrosis and bronchiectasis. A recent Cochrane review examined 4 small studies that suggest that nebulized 3% HS may reduce length of hospital stay and improve clinical severity scores in infants with acute viral bronchiolitis. None of these studies have explored the use of nebulized HS in the emergency department (ED). A recent study examined the use of a single nebulized treatment of epinephrine mixed in 3% HS in 46 infants less than 12 months presenting to the ED with bronchiolitis. This study did not find a difference between epinephrine diluted in normal saline compared to epinephrine diluted in 3% HS. Despite no effect on clinical score, the investigators did note a trend toward decreased rates of hospitalization. Furthermore, since this was the first ED study and the first negative study, the authors concluded that further investigation is necessary to determine if HS has a role in the management of acute bronchiolitis. The purpose of the current study is to determine whether nebulized 3% HS improves respiratory distress in children 2-23 months presenting to the ED with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol. Given the tremendous clinical and financial burden of bronchiolitis, any effective therapy, particularly one that is inexpensive, has the potential to result in significant health care savings. If nebulized 3% HS improved clinical scores in the ED, this may provide an inexpensive, safe and effective therapy for children with bronchiolitis in the acute care setting.

Interventions

4 mL of nebulized 3% saline once

4 mL of 0.9% nebulized normal saline once

Sponsors

Children's Hospital of Philadelphia
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
2 Months to 23 Months
Healthy volunteers
No

Inclusion criteria

* Age 8 weeks through 23 months * First episode of wheezing associated with respiratory distress and upper respiratory tract infection. * Respiratory Distress Assessment Instrument (RDAI) rating of ≥4 and ≤15 after initial albuterol nebulization per standard care * Pediatric Emergency Medicine (PEM) physician does not plan additional bronchodilator therapy within the hour after initial assessment. * Parental/guardian permission (informed consent)

Exclusion criteria

* Subjects with prior history of wheezing or asthma or who have received bronchodilator therapy prior to the current illness * Chronic lung or heart disease * Critically ill infants requiring immediate airway stabilization * Non-English speaking parent/guardian * Inability to take nebulized medications

Design outcomes

Primary

MeasureTime frameDescription
Respiratory Assessment Change Score (RACS)Baseline and 1 hourThe Respiratory Assessment Change Score (RACS) assesses change in respiratory status using the change in the Respiratory Distress Assessment Instrument (RDAI) and a standardized change in respiratory rate, with points being assigned by change increments of 10%. Thus, a change in respiratory rate of ≤5% from baseline counted as a change of 0 units, decrease/increase of 6% to 15% counted as improvement/deterioration of 1 unit, etc. The overall RACS is the arithmetic sum of the RDAI change and the standardized respiratory rate change between assessments with a decrease in RACS signifying improvement.

Secondary

MeasureTime frame
Rate of Hospitalization1 day
Respiratory Rate ChangeBaseline and 1 hour
Oxygen Saturation ChangeBaseline and 1 hour
Parental Perception of Improvement of Breathing After Study Medication1 hour

Countries

United States

Participant flow

Participants by arm

ArmCount
Nebulized 3% Saline
Nebulized 3% saline: 4 mL of nebulized 3% saline once
31
Nebulized 0.9% Normal Saline
Nebulized 0.9% Normal Saline: 4 mL of 0.9% nebulized normal saline once
31
Total62

Baseline characteristics

CharacteristicNebulized 3% SalineTotalNebulized 0.9% Normal Saline
Age, Continuous7.2 months
STANDARD_DEVIATION 5.1
6.6 months
STANDARD_DEVIATION 4.3
6.1 months
STANDARD_DEVIATION 3.6
Days of Symptoms3.4 days
STANDARD_DEVIATION 3.7
3.4 days
STANDARD_DEVIATION 3.1
3.4 days
STANDARD_DEVIATION 2.4
Eczema History
No
21 participants44 participants23 participants
Eczema History
Unknown
2 participants3 participants1 participants
Eczema History
Yes
8 participants15 participants7 participants
Family History of Atopy
No
7 participants13 participants6 participants
Family History of Atopy
Unknown
2 participants3 participants1 participants
Family History of Atopy
Yes
22 participants46 participants24 participants
Heart Rate153.4 beats per minute
STANDARD_DEVIATION 18.4
156.5 beats per minute
STANDARD_DEVIATION 20
159.3 beats per minute
STANDARD_DEVIATION 21.9
ICU History
No
23 participants50 participants27 participants
ICU History
Unknown
2 participants2 participants0 participants
ICU History
Yes
6 participants10 participants4 participants
Oxygen Saturation95.4 percent
STANDARD_DEVIATION 3.8
95.9 percent
STANDARD_DEVIATION 3.7
96.3 percent
STANDARD_DEVIATION 3.7
Physician Clinical Impression
Mild
9 participants20 participants11 participants
Physician Clinical Impression
Missing
1 participants1 participants0 participants
Physician Clinical Impression
Moderate
21 participants41 participants20 participants
Race/Ethnicity, Customized
African-American
24 participants47 participants23 participants
Race/Ethnicity, Customized
Asian
2 participants2 participants0 participants
Race/Ethnicity, Customized
Hispanic
1 participants6 participants5 participants
Race/Ethnicity, Customized
Missing
1 participants1 participants0 participants
Race/Ethnicity, Customized
White
3 participants6 participants3 participants
Respiratory Distress Assessment Instrument Score7.8 units on a scale
STANDARD_DEVIATION 2.6
7.6 units on a scale
STANDARD_DEVIATION 2.5
7.4 units on a scale
STANDARD_DEVIATION 2.5
Respiratory Rate49.6 breaths per minute
STANDARD_DEVIATION 12.4
50.9 breaths per minute
STANDARD_DEVIATION 12.3
52.4 breaths per minute
STANDARD_DEVIATION 12.4
Sex: Female, Male
Female
16 Participants34 Participants18 Participants
Sex: Female, Male
Male
15 Participants28 Participants13 Participants
Smokers in Household
No
14 participants31 participants17 participants
Smokers in Household
Unknown
0 participants1 participants1 participants
Smokers in Household
Yes
17 participants30 participants13 participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 310 / 31
serious
Total, serious adverse events
0 / 310 / 31

Outcome results

Primary

Respiratory Assessment Change Score (RACS)

The Respiratory Assessment Change Score (RACS) assesses change in respiratory status using the change in the Respiratory Distress Assessment Instrument (RDAI) and a standardized change in respiratory rate, with points being assigned by change increments of 10%. Thus, a change in respiratory rate of ≤5% from baseline counted as a change of 0 units, decrease/increase of 6% to 15% counted as improvement/deterioration of 1 unit, etc. The overall RACS is the arithmetic sum of the RDAI change and the standardized respiratory rate change between assessments with a decrease in RACS signifying improvement.

Time frame: Baseline and 1 hour

ArmMeasureValue (MEAN)
Nebulized 3% SalineRespiratory Assessment Change Score (RACS)-1.5 units on a scale
Nebulized 0.9% Normal SalineRespiratory Assessment Change Score (RACS)-4 units on a scale
p-value: 0.01t-test, 2 sided
Secondary

Oxygen Saturation Change

Time frame: Baseline and 1 hour

ArmMeasureValue (MEAN)
Nebulized 3% SalineOxygen Saturation Change1.1 percent
Nebulized 0.9% Normal SalineOxygen Saturation Change0.1 percent
p-value: 0.36t-test, 2 sided
Secondary

Parental Perception of Improvement of Breathing After Study Medication

Time frame: 1 hour

ArmMeasureValue (NUMBER)
Nebulized 3% SalineParental Perception of Improvement of Breathing After Study Medication50 percentage of participants
Nebulized 0.9% Normal SalineParental Perception of Improvement of Breathing After Study Medication54.8 percentage of participants
p-value: 0.62Chi-squared
Secondary

Rate of Hospitalization

Time frame: 1 day

ArmMeasureValue (NUMBER)
Nebulized 3% SalineRate of Hospitalization71 percentage of participants
Nebulized 0.9% Normal SalineRate of Hospitalization64.5 percentage of participants
p-value: 0.86Chi-squared
Secondary

Respiratory Rate Change

Time frame: Baseline and 1 hour

ArmMeasureValue (MEAN)
Nebulized 3% SalineRespiratory Rate Change-1.8 breaths per minute
Nebulized 0.9% Normal SalineRespiratory Rate Change-9.8 breaths per minute
p-value: 0.02t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026