Bronchiolitis
Conditions
Keywords
bronchiolitis, hypertonic saline
Brief summary
This study aims to examine the effect of nebulized 3% hypertonic saline in the treatment of viral bronchiolitis. The investigators hypothesize that nebulized 3% saline will decrease rate of hospital admission, decrease clinical severity scores, and decrease length of stay.
Detailed description
Bronchiolitis is the most common viral respiratory infection in young children and infants. It is responsible for hundreds of thousands of outpatient visits and hospitalizations every year. Hypertonic saline may decrease swelling in the lung tissue, improve the patient's ability to clear secretions, and decrease nasal congestion. Hypertonic saline nebulizations have already been used effectively in patients with cystic fibrosis and in a few small trials on infants with bronchiolitis. Patients who come to the emergency department or inpatient ward of two urban free-standing pediatric hospitals in California between December and April and are diagnosed with bronchiolitis will be randomized into two groups- the control group will receive nebulized 0.9% normal saline, while the study group will receive nebulized 3% hypertonic saline. Nebulizations will be pretreated with albuterol, to prevent the theoretical risk of increased wheezing in patients with undiagnosed underlying asthma. Patients will be given up to 3 nebulizations in the emergency department, after which time the attending physician will decide whether admission to the hospital is required. Patients who are admitted will continue to receive the same nebulized treatment every 8 hours until discharged. Additional interventions such as epinephrine treatments and antibiotics can be ordered as indicated by the patient care team. Investigators will measure symptom severity before and after treatments using the respiratory distress assessment instrument (RDAI). The investigators will compare rates of being admitted to the hospital in each group. The investigators will also compare RDAI scores, average length of stay, number of additional respiratory treatments needed, number of hours requiring oxygen, amount of IV fluid needed, and frequency of adverse effects. The investigators hypothesize that nebulized hypertonic saline will be a safe, cost-effective, and efficacious therapy which can be utilized in the outpatient setting to prevent hospital admission, as well as decrease length of stay for patients who require admission. Given the significant disease burden of viral bronchiolitis, the potential impact is substantial.
Interventions
4 ml inhaled q8h
DRUGNebulized 0.9% saline
normal saline
Sponsors
UCSF Benioff Children's Hospital Oakland
Thrasher Research Fund
Children's Hospital Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
* clinical diagnosis of viral bronchiolitis * between November and April
Exclusion criteria
* prematurity \< 34 weeks * chronic lung disease * congenital heart disease * history of wheezing, asthma or albuterol use * tracheostomy status * need for intensive care of assisted ventilation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Admission Rate | 1 day | Patients enrolled in the ED who required inpatient admission. Patients who required admission but were transferred to another facility due to lack of available beds were considered admitted for this outcome. Note, neither study site has an observation unit. |
| Length of Stay | 1 month | Length of stay defined as date of discharge minus date of admission (whole days) |
| Change in RDAI Score | 1 Hour | The Respiratory Distress Assessment Instrument (RDAI) is a respiratory severity score ranging from a low score of 0 to maximum score of 17. Lower scores indicate more mild symptoms; mild disease (0-6), moderate disease (7-11), and severe (12-17). A decrease in score of 2 is considered clinically significant improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hours of Oxygen Use | 14 days | Hours requiring supplemental oxygen for admitted patients. |
| IV Fluid Use | 14 days | IV fluid volume administered during entire hospitalization, in mL/kg |
| Number of Participants With Supplemental Medication Use | 14 days | patients who received supplemental albuterol, ipratropium, or epinephrine inhaled treatment (other than pre-treatment for study med) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited beginning March 2008 and April 2011, only during months of bronchiolitis season (November through April). Recruitment occurred in the emergency department and general medical inpatient units at 2 urban tertiary free-standing children's hospitals in the U.S.
Pre-assignment details
No patients were excluded after enrollment but before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Hypertonic Saline 3% NaCl, 4 ml, via updraft wall nebulizer:
* In ED: every 20 minutes up to 3 doses
* In Inpatient: every 8 hours until discharge | 230 |
| Normal Saline 0.9% NaCl, 4 ml, via updraft wall nebulizer:
* In ED: every 20 minutes up to 3 doses
* In Inpatient: every 8 hours until discharge | 217 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | ICU admission | 4 | 6 |
| Overall Study | Left before receiving first dose | 7 | 6 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Transfer to outside facility | 3 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Normal Saline | Hypertonic Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 217 Participants | 230 Participants | 447 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 0.53 years STANDARD_DEVIATION 0.43 | 0.55 years STANDARD_DEVIATION 0.42 | 0.54 years STANDARD_DEVIATION 0.44 |
| Region of Enrollment United States | 217 participants | 230 participants | 447 participants |
| Sex: Female, Male Female | 98 Participants | 95 Participants | 193 Participants |
| Sex: Female, Male Male | 119 Participants | 135 Participants | 254 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 231 | 0 / 216 |
| other Total, other adverse events | 5 / 231 | 8 / 216 |
| serious Total, serious adverse events | 0 / 231 | 0 / 216 |
Outcome results
Primary
Admission Rate
Patients enrolled in the ED who required inpatient admission. Patients who required admission but were transferred to another facility due to lack of available beds were considered admitted for this outcome. Note, neither study site has an observation unit.
Time frame: 1 day
Population: Analysis for this outcome only includes patients who were enrolled in the ED, and not patients enrolled in the inpatient setting.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hypertonic Saline | Admission Rate | Discharged | 141 participants |
| Hypertonic Saline | Admission Rate | Admitted | 55 participants |
| Normal Saline | Admission Rate | Discharged | 107 participants |
| Normal Saline | Admission Rate | Admitted | 76 participants |
Primary
Change in RDAI Score
The Respiratory Distress Assessment Instrument (RDAI) is a respiratory severity score ranging from a low score of 0 to maximum score of 17. Lower scores indicate more mild symptoms; mild disease (0-6), moderate disease (7-11), and severe (12-17). A decrease in score of 2 is considered clinically significant improvement.
Time frame: 1 Hour
Population: Excludes patients who did not receive any doses of study medication (17), patients missing pre-tx score (7), post-tx score (4), or both (1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hypertonic Saline | Change in RDAI Score | 1.032 units on a scale | Standard Deviation 2.087 |
| Normal Saline | Change in RDAI Score | 0.8557 units on a scale | Standard Deviation 1.65 |
Primary
Length of Stay
Length of stay defined as date of discharge minus date of admission (whole days)
Time frame: 1 month
Population: Analysis for this outcome only includes patients who were admitted to inpatient status at the enrolling hospital and not transferred out.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hypertonic Saline | Length of Stay | 2.87 Days | Standard Deviation 2 |
| Normal Saline | Length of Stay | 2.86 Days | Standard Deviation 1.73 |
Secondary
Hours of Oxygen Use
Hours requiring supplemental oxygen for admitted patients.
Time frame: 14 days
Population: Excludes patients withdrawn by investigator due to ICU admission or ineligible condition (12), withdrawn by parent (6), and missing data (3)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hypertonic Saline | Hours of Oxygen Use | 32.88 hours | Standard Deviation 39.99 |
| Normal Saline | Hours of Oxygen Use | 31.39 hours | Standard Deviation 44.54 |
Secondary
IV Fluid Use
IV fluid volume administered during entire hospitalization, in mL/kg
Time frame: 14 days
Population: Excludes patients withdrawn by investigator due to ICU admission or ineligible condition (12), withdrawn by parent (6), and missing data (3)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hypertonic Saline | IV Fluid Use | 51.38 mL/kg | Standard Deviation 90.15 |
| Normal Saline | IV Fluid Use | 59.73 mL/kg | Standard Deviation 107.1 |
Secondary
Number of Participants With Supplemental Medication Use
patients who received supplemental albuterol, ipratropium, or epinephrine inhaled treatment (other than pre-treatment for study med)
Time frame: 14 days
Population: 230 patients were allocated to the 3% group; one patient allocated to the 0.9% group received 3% so was added to the 3% group for analysis, totaling 231 patients. The 0.9% group originally had 217 patients but after moving this patient to the 3% group, there are now 216 patients in the 0.9% group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypertonic Saline | Number of Participants With Supplemental Medication Use | 39 Participants |
| Normal Saline | Number of Participants With Supplemental Medication Use | 39 Participants |