Respiratory Failure
Conditions
Keywords
pediatric, mucolytic, respiratory failure, atelectasis, hypertonic saline
Brief summary
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
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.
Interventions
DRUGHypertonic saline (3%)
3mL of HTS given via nebulizer every 6hrs
3mL of normal saline given via nebulizer every 6hrs
Sponsors
University Hospitals Cleveland Medical Center
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 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of Mechanical Ventilation | typically 4 days - 2 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wheezing | during mechanical ventilation (typically 4 days - 2 weeks) | as dichotomous outcome (yes/no) following drug administration |
| ICU Length of Stay | during hospitalization (typically 4 days - 2 weeks) | — |
| Hospital Length of Stay | during hospitalization (typically 4 days - 2 weeks) | — |
| Atelectasis | during mechanical ventilation (typically 4 days - 2 weeks) | 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. |
| Dynamic Compliance | during mechanical ventilation (typically 4 days - 2 weeks) | measured in ml/cm H20/kg using parameters on mechanical ventilator |
| Oxygenation | during mechanical ventilation (typically 4 days - 2 weeks) | SaO2/FiO2. This is a measure of how will the lungs are providing oxygen to the body. Higher ratios reflect better lung function. |
| Dead Space | during mechanical ventilation (typically 4 days - 2 weeks) | 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. |
| Change in Serum Sodium From Baseline | during hospitalization (typically 4 days - 2 weeks) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days
Placebo (0.9% saline) | 9 |
| Hypertonic Saline Hypertonic saline (3%), 3mL every 6hrs for up to 7 days
Hypertonic saline (3%) | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Hypertonic Saline | Total |
|---|---|---|---|
| Age, Continuous | 26 weeks | 12.7 weeks | 17.9 weeks |
| PEEP (positive end-expiratory pressure) | 5 cm-H20 | 7 cm-H20 | 6 cm-H20 |
| Race/Ethnicity, Customized African-American | 4 participants | 5 participants | 9 participants |
| Race/Ethnicity, Customized Caucasian | 5 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 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 / 9 |
| serious Total, serious adverse events | 0 / 9 | 2 / 9 |
Outcome results
Primary
Duration of Mechanical Ventilation
Time frame: typically 4 days - 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Mechanical Ventilation | 129.5 hours |
| Hypertonic Saline | Duration of Mechanical Ventilation | 208.1 hours |
Secondary
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.
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Atelectasis | 4.67 units on a scale |
| Hypertonic Saline | Atelectasis | 4 units on a scale |
Secondary
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.
Time frame: during hospitalization (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Serum Sodium From Baseline | 1 mEq/L |
| Hypertonic Saline | Change in Serum Sodium From Baseline | -1.5 mEq/L |
Secondary
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.
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Dead Space | 29 percentage of lung volume |
| Hypertonic Saline | Dead Space | 37 percentage of lung volume |
Secondary
Dynamic Compliance
measured in ml/cm H20/kg using parameters on mechanical ventilator
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Dynamic Compliance | 6.52 mL/kg/cm-H20 |
| Hypertonic Saline | Dynamic Compliance | 4.47 mL/kg/cm-H20 |
Secondary
Hospital Length of Stay
Time frame: during hospitalization (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Hospital Length of Stay | 15 days |
| Hypertonic Saline | Hospital Length of Stay | 17 days |
Secondary
ICU Length of Stay
Time frame: during hospitalization (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | ICU Length of Stay | 8 days |
| Hypertonic Saline | ICU Length of Stay | 12 days |
Secondary
Oxygenation
SaO2/FiO2. This is a measure of how will the lungs are providing oxygen to the body. Higher ratios reflect better lung function.
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Oxygenation | 239 ratio |
| Hypertonic Saline | Oxygenation | 188 ratio |
Secondary
Wheezing
as dichotomous outcome (yes/no) following drug administration
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Wheezing | 3 percentage of drug doses w/ wheezing |
| Hypertonic Saline | Wheezing | 1 percentage of drug doses w/ wheezing |