Clinical trial NCT01945944: Nebulized Hypertonic Saline for Mechanically Ventilated Children
Official title: Nebulized Hypertonic Saline for Mechanically Ventilated Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Failure
Keywords: pediatric
mucolytic
respiratory failure
atelectasis
hypertonic saline
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
First posted: 2013-09-19
Enrollment: 18
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Mechanical Ventilation
timeFrame: typically 4 days - 2 weeks
Secondary outcomes:
measure: Atelectasis
timeFrame: during mechanical ventilation (typically 4 days - 2 weeks)
measure: Wheezing
timeFrame: during mechanical ventilation (typically 4 days - 2 weeks)
measure: ICU Length of Stay
timeFrame: during hospitalization (typically 4 days - 2 weeks)
measure: Hospital Length of Stay
timeFrame: during hospitalization (typically 4 days - 2 weeks)
measure: Change in Serum Sodium From Baseline
timeFrame: during hospitalization (typically 4 days - 2 weeks)
measure: Dynamic Compliance
timeFrame: during mechanical ventilation (typically 4 days - 2 weeks)
measure: Oxygenation
timeFrame: during mechanical ventilation (typically 4 days - 2 weeks)
measure: Dead Space
timeFrame: during mechanical ventilation (typically 4 days - 2 weeks)
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital (of Univ. Hospitals Case Med. Center)
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Steven L Shein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.