Nebulized Hypertonic Saline for Mechanically Ventilated Children

Study Overview
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Brief Summary
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Children who need to be on a ventilator often have thick secretions/mucus in their lungs. These secretions can obstruct the breathing tube and their windpipe, which can worsen lung function and prolong the need for the ventilator. Hypertonic saline is a medicine that is used to thin out secretions in patients with cystic fibrosis (and other conditions). We hypothesize that having children on a ventilator inhale this medication will shorten the amount of time that they need to be on the ventilator.

Detailed Description
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Recent pediatric data shows that less than 80% of children mechanically ventilated for ≥ 96 hours survived to PICU discharge, while 100% of children mechanically ventilated for < 96 hours survived to PICU discharge. Interventions that decrease duration of mechanical ventilation may improve outcome by limiting ventilator-induced lung injury, sedative medication usage and ventilator-associated pneumonia. Obstructive airway secretions may prolong mechanical ventilation by causing atelectasis and endotracheal tube obstruction, with resultant cardio-respiratory instability. Nebulized hypertonic saline (HTS) is used to decrease mucus viscosity and increase mucociliary clearance in patients with diseases such as cystic fibrosis and bronchiolitis, and has been used to enhance airway clearance in mechanically ventilated children. Administering nebulized HTS to mechanically ventilated children may facilitate airway clearance and shorten mechanical ventilation. In a randomized study of children < 2 years old following cardiac surgery, patients given dornase, another mucolytic agent, had a significantly decreased duration of mechanical ventilation versus those given saline placebo (52 hrs vs. 82 hrs). HTS may be even more effective, as mechanically ventilated newborns with persistent atelectasis had more improvement in radiographic findings and oxygen saturation when randomized to receive hypertonic saline compared to those randomized to receive dornase. This may be because dornase may only be effective in patients with leukocytes or bacterial present in tracheal aspirates, while HTS may be effective in all ventilated patients. Further study of the impact of prophylactic mucolytic therapy on the duration of mechanical ventilation in children is warranted.

Official Title
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Nebulized Hypertonic Saline for Mechanically Ventilated Children

Conditions
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Respiratory Failure

Intervention / Treatment
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* Drug: Hypertonic saline (3%)
* Drug: Placebo (0.9% saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: invasive mechanical ventilation of < 12 hrs duration prior to enrollment expected duration of mechanical ventilation of > 48hrs from enrollment age < 18yo Exclusion Criteria: inclusion in another clinical study cystic fibrosis status asthmaticus pulmonary hemorrhage/contusion home O2 use home non-invasive positive pressure (CPAP/BiPAP) ventilation use pre-existing tracheostomy prescription of mucolytic medication by primary clinical team allergy to inhaled saline/hypertonic saline or albuterol

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days | Drug: Placebo (0.9% saline)<br>* 3mL of normal saline given via nebulizer every 6hrs<br>* Other names: normal saline;|
| Experimental: Hypertonic Saline<br>Hypertonic saline (3%), 3mL every 6hrs for up to 7 days | Drug: Hypertonic saline (3%)<br>* 3mL of HTS given via nebulizer every 6hrs<br>* Other names: 3% saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Mechanical Ventilation |  | typically 4 days - 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dead Space | in % of tidal volume, using parameters on mechanical ventilator. Dead space is a measure of how much of the lung is not able to move air into and out of the body. Higher levels of dead space reflect higher levels of lung dysfunction. | during mechanical ventilation (typically 4 days - 2 weeks) | 
| Atelectasis | using chest x ray score. The score measures the amount of lung collapse (atelectasis) observed on a chest x-ray. For each of the 5 lung lobes, 1 point is given for linear atelectasis, 2 points for sub-segmental atelectasis and 3 points for lobar atelectasis. The range is 0-15 points, with higher scores reflecting more severe lung collapse. | during mechanical ventilation (typically 4 days - 2 weeks) | 
| Wheezing | as dichotomous outcome (yes/no) following drug administration | during mechanical ventilation (typically 4 days - 2 weeks) | 
| ICU Length of Stay |  | during hospitalization (typically 4 days - 2 weeks) | 
| Hospital Length of Stay |  | during hospitalization (typically 4 days - 2 weeks) | 
| Change in Serum Sodium From Baseline | The baseline sodium was the last level measured prior to study initiation, typically within 24hrs of study initiation. The change in blood sodium level was calculated as the difference between the mean post-enrollment sodium level during ICU care and the sodium level at enrollment. | during hospitalization (typically 4 days - 2 weeks) | 
| Dynamic Compliance | measured in ml/cm H20/kg using parameters on mechanical ventilator | during mechanical ventilation (typically 4 days - 2 weeks) | 
| Oxygenation | SaO2/FiO2. This is a measure of how will the lungs are providing oxygen to the body. Higher ratios reflect better lung function. | during mechanical ventilation (typically 4 days - 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, mucolytic, respiratory failure, atelectasis, hypertonic saline