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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days |
|
| Hypertonic Saline | Experimental | Hypertonic saline (3%), 3mL every 6hrs for up to 7 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypertonic saline (3%) | Drug | 3mL of HTS given via nebulizer every 6hrs |
|
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Mechanical Ventilation | typically 4 days - 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven L Shein, MD | University Hospitals Cleveland Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rainbow Babies and Children's Hospital (of Univ. Hospitals Case Med. Center) | Cleveland | Ohio | 44106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21760567 | Background | Payen V, Jouvet P, Lacroix J, Ducruet T, Gauvin F. Risk factors associated with increased length of mechanical ventilation in children. Pediatr Crit Care Med. 2012 Mar;13(2):152-7. doi: 10.1097/PCC.0b013e3182257a24. | |
| 16265663 | Background | Riethmueller J, Borth-Bruhns T, Kumpf M, Vonthein R, Wiskirchen J, Stern M, Hofbeck M, Baden W. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol. 2006 Jan;41(1):61-6. doi: 10.1002/ppul.20298. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days Placebo (0.9% saline) |
| FG001 | Hypertonic Saline | Hypertonic saline (3%), 3mL every 6hrs for up to 7 days Hypertonic saline (3%) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days Placebo (0.9% saline) |
| BG001 | Hypertonic Saline | Hypertonic saline (3%), 3mL every 6hrs for up to 7 days Hypertonic saline (3%) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Duration of Mechanical Ventilation | Posted | Median | Inter-Quartile Range | hours | typically 4 days - 2 weeks |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days Placebo (0.9% saline) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Desaturation (oxygen) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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As shown above, baseline lung function (as measured by PEEP) was worse in the treatment (HTS) group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven Shein, MD | Rainbow Babies and Children's Hospital | 216-844-3310 | drstevenshein@gmail.com |
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| ID | Term |
|---|---|
| D012131 | Respiratory Insufficiency |
| D001261 | Pulmonary Atelectasis |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D012462 | Saline Solution, Hypertonic |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D006982 | Hypertonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
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| Placebo (0.9% saline) | Drug | 3mL of normal saline given via nebulizer every 6hrs |
|
|
| 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) |
| 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) |
| 20831650 | Background | Dilmen U, Karagol BS, Oguz SS. Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns. Pediatr Int. 2011 Jun;53(3):328-31. doi: 10.1111/j.1442-200X.2010.03245.x. |
| 19489944 | Background | Prodhan P, Greenberg B, Bhutta AT, Hyde C, Vankatesan A, Imamura M, Jaquiss RD, Dyamenahalli U. Recombinant human deoxyribonuclease improves atelectasis in mechanically ventilated children with cardiac disease. Congenit Heart Dis. 2009 May-Jun;4(3):166-73. doi: 10.1111/j.1747-0803.2009.00289.x. |
| 18843717 | Background | Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006458. doi: 10.1002/14651858.CD006458.pub2. |
| 22610452 | Background | Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012 Jun 6;307(21):2269-77. doi: 10.1001/jama.2012.5214. |
| 16421364 | Background | Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900. |
| 22114907 | Background | Altunhan H, Annagur A, Pekcan S, Ors R, Koc H. Comparing the efficacy of nebulizer recombinant human DNase and hypertonic saline as monotherapy and combined treatment in the treatment of persistent atelectasis in mechanically ventilated newborns. Pediatr Int. 2012 Feb;54(1):131-6. doi: 10.1111/j.1442-200X.2011.03519.x. |
| 22413805 | Background | Youness HA, Mathews K, Elya MK, Kinasewitz GT, Keddissi JI. Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients. J Aerosol Med Pulm Drug Deliv. 2012 Dec;25(6):342-8. doi: 10.1089/jamp.2011.0954. Epub 2012 Mar 13. |
| Withdrawal by Subject |
|
| BG002 | Total | Total of all reporting groups |
| weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| PEEP (positive end-expiratory pressure) | Median | Inter-Quartile Range | cm-H20 |
|
|
| 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. | Posted | Median | Inter-Quartile Range | units on a scale | during mechanical ventilation (typically 4 days - 2 weeks) |
|
|
|
| Secondary | Wheezing | as dichotomous outcome (yes/no) following drug administration | Posted | Number | percentage of drug doses w/ wheezing | during mechanical ventilation (typically 4 days - 2 weeks) |
|
|
|
| Secondary | ICU Length of Stay | Posted | Median | Inter-Quartile Range | days | during hospitalization (typically 4 days - 2 weeks) |
|
|
|
| Secondary | Hospital Length of Stay | Posted | Median | Inter-Quartile Range | days | during hospitalization (typically 4 days - 2 weeks) |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | mEq/L | during hospitalization (typically 4 days - 2 weeks) |
|
|
|
| Secondary | Dynamic Compliance | measured in ml/cm H20/kg using parameters on mechanical ventilator | Posted | Median | Inter-Quartile Range | mL/kg/cm-H20 | during mechanical ventilation (typically 4 days - 2 weeks) |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | ratio | during mechanical ventilation (typically 4 days - 2 weeks) |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | percentage of lung volume | during mechanical ventilation (typically 4 days - 2 weeks) |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Hypertonic Saline | Hypertonic saline (3%), 3mL every 6hrs for up to 7 days Hypertonic saline (3%) | 2 | 9 | 0 | 9 |
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| D006851 |
| Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |