Nebulized Hypertonic Saline for Mechanically Ventilated Children

Respiratory Failure Clinical Trial

Official title:

Nebulized Hypertonic Saline for Mechanically Ventilated Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01945944
• Other study ID #: 08-13-11
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 12, 2013
• Last updated: December 8, 2014
• Start date: October 2013
• Est. completion date: May 2014

Study information

• Verified date: December 2014
• Source: University Hospital Case Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• Hypertonic saline (3%)

• Placebo (0.9% saline)

Locations

Country	Name	City	State
United States	Rainbow Babies and Children's Hospital (of Univ. Hospitals Case Med. Center)	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Case Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (9)

Altunhan H, Annagür A, Pekcan S, Ors R, Koç 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum in: Pediatr Pulmonol. 2006 Apr;41(4):388. — View 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. — View 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. — View 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. Review. Update in: Cochrane Database Syst Rev. 2013;7:CD006458. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of mechanical ventilation		typically 4 days - 2 weeks	No
Secondary	atelectasis	using chest x ray score	during mechanical ventilation (typically 4 days - 2 weeks)	No
Secondary	wheezing	as dichotomous outcome (yes/no) following drug administration	during mechanical ventilation (typically 4 days - 2 weeks)	Yes
Secondary	ICU length of stay		during hospitalization (typically 4 days - 2 weeks)	No
Secondary	hospital length of stay		during hospitalization (typically 4 days - 2 weeks)	No
Secondary	serum sodium level		during hospitalization (typically 4 days - 2 weeks)	Yes
Secondary	dynamic compliance	measured in ml/cm H20/kg using parameters on mechanical ventilator	during mechanical ventilation (typically 4 days - 2 weeks)	No
Secondary	oxygenation	PaO2/FiO2, SaO2/FiO2	during mechanical ventilation (typically 4 days - 2 weeks)	Yes
Secondary	dead space	in % of tidal volume, using parameters on mechanical ventilator	during mechanical ventilation (typically 4 days - 2 weeks)	Yes