Bronchiolitis
Conditions
Keywords
Bronchiolitis, Therapeutics, Saline Solution, Hypertonic
Brief summary
Acute viral bronchiolitis is an extremely common childhood disease, responsible for approximately 17% of childhood admissions to hospital per year, with an annually cost that reaches U$ 500 million. Despite being a well known disease among pediatricians, there are few, if any, effective treatment options apart from oxygen supplementation and adequate hydration. The purpose of this study is to determine wether nebulized hypertonic saline (3%) is more effective than normal saline (0,9%) when used in repeated doses during the first 24 hours of in-hospital treatment.
Detailed description
Acute viral bronchiolitis is a lower airway infection, caused manly by Respiratory Syncytial Virus. Near 1% of children up to 2 years of age get it with sufficient severity to warrant hospital admission, with an annual cost of about U$ 500 million in the US, superior, for instance, than cystic fibrosis annual cost. Despite the physiopathology and clinical course being well known among pediatricians, few therapeutical options other than adequate hydration and oxygen supplementation have proven to be effective Corticosteroids are not effective and bronchodilators are controversial, and treatment is still mostly empiric and lacking evidence. In the last few years, there has been a growing interest in the use of nebulized hypertonic saline (HS) as a promising approach. The rational is that HS would help reducing edema and mucus viscosity, enhancing its rheologic properties. Recent studies suggest that HS could reduce up to 1 day (25%) of time until discharge in admitted patients. In the Emergency Department, HS was not superior to other forms of treatment, but these studies lack power and similarities to draw further conclusions. Also, time of treatment and ideal interval between doses are not known as yet. To our knowledge, few if any studies have assessed patients with an intermediary (up to 24h) time of stay, namely a short stay ward attached to an emergency department. Thus, we have endeavoured to determine if repeated doses of nebulized HS are superior to nebulized normal saline (NS) during the first 24 hour of treatment, when considered: rate of admission, time until discharge, time until attain discharge criteria, and rate of readmission after discharge. Furthermore, most studies use HS associated to a bronchodilator, because of a theoretical possibility that HS alone could induce bronchoconstriction and worsen respiratory symptoms. However, recent studies have shown that HS use without bronchodilators have not caused any worsening of symptoms in bronchiolitis patients. Therefore, we propose to study the effect of HS alone, without the adding of bronchodilators, which would minimize bias in the treatment group.
Interventions
DRUGHypertonic Saline
Sodium Chloride 3% solution, previously prepared in 5 mL syringes.
RADIATIONChest X-Ray
OTHERRespiratory virus screening test
Immunofluorescence analysis of nasal aspirate
Sponsors
University of Sao Paulo
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 12 Months
Healthy volunteers
No
Inclusion criteria
* Age \< 12 months * Clinical diagnosis of bronchiolitis (viral respiratory disease and wheezing) * First episode of wheezing in life * Moderate respiratory distress, defined as 2 of the following: Sat \<93%, respiratory rate \>60 and/or RDAI score \>4
Exclusion criteria
* Previous episodes of wheezing in history * Use of bronchodilators, corticosteroids or antibiotics in the 24 hours prior to admission or at any time during treatment. * Other clinical conditions such as: prematurity, bronchopulmonary dysplasia, cystic fibrosis, cardiac disease or immunodeficiencies. * detection of alveolar infiltrates suggestive of pneumonia in radiologic examination * respiratory impairment requiring mechanical ventilation on arrival to hospital.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Admission | 24 hours | Patients staying longer than 24h are considered to be admitted to ward. |
| Time to Attain Discharge Criteria | 24 hours | Discharge criteria are: Room air saturation \>94% AND respiratory rate \< 60 AND Respiratory Distress Assessment Instrument (RDAI) score inferior than 4, maintained over a 4 hour period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Discharge | 24 hours | Actual time to discharge was considered of secondary importance as it can be influenced by individual considerations like patient age or time of the day. |
| Rate of Readmission After Discharge | 5 days | The mere attendance to the Emergency Department will not be isolately considered, as it may be due to a scheduled reevaluation. |
| Incidence of Adverse Effects | 24 hours | Any adverse effects directly attributable to treatment shall be noted. Mere lack of improve or worsening of symptoms attributable to the disease clinical course will not be considered as adverse effects. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Saline Patients will receive inhaled normal saline, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat\>94% AND respiratory rate \<60 AND RDAI score \<4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital.
Chest X-Ray
Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate | 16 |
| Hypertonic Saline Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat\>94% AND respiratory rate \<60 AND RDAI score \<4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital.
Hypertonic Saline: Sodium Chloride 3% solution, previously prepared in 5 mL syringes.
Chest X-Ray
Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate | 15 |
| Total | 31 |
Baseline characteristics
| Characteristic | Normal Saline | Hypertonic Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Brazil | 16 participants | 15 participants | 31 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 14 |
| serious Total, serious adverse events | 0 / 9 | 0 / 14 |
Outcome results
Primary
Rate of Admission
Patients staying longer than 24h are considered to be admitted to ward.
Time frame: 24 hours
Population: Number of participants analyzed was too small to obtain statistic significance
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | Rate of Admission | 3 participants |
| Hypertonic Saline | Rate of Admission | 6 participants |
Primary
Time to Attain Discharge Criteria
Discharge criteria are: Room air saturation \>94% AND respiratory rate \< 60 AND Respiratory Distress Assessment Instrument (RDAI) score inferior than 4, maintained over a 4 hour period.
Time frame: 24 hours
Secondary
Incidence of Adverse Effects
Any adverse effects directly attributable to treatment shall be noted. Mere lack of improve or worsening of symptoms attributable to the disease clinical course will not be considered as adverse effects.
Time frame: 24 hours
Population: Number of patients too small to achieve statistical significance
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | Incidence of Adverse Effects | 0 participants |
| Hypertonic Saline | Incidence of Adverse Effects | 0 participants |
Secondary
Rate of Readmission After Discharge
The mere attendance to the Emergency Department will not be isolately considered, as it may be due to a scheduled reevaluation.
Time frame: 5 days
Secondary
Time to Discharge
Actual time to discharge was considered of secondary importance as it can be influenced by individual considerations like patient age or time of the day.
Time frame: 24 hours