Work of Breathing During Non-invasive Ventilation in Premature Neonates

NCT02788110 | Completed DMC

• 1 other identifier: IRB 205507
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Non-invasive forms of respiratory support have been developed to manage respiratory distress and failure in premature newborns without exposing them to the risks associated with invasive mechanical ventilation. It has been difficult to synchronize non-invasive ventilation due to the large air leaks, high respiratory rates, and small tidal volumes inherent to this interface and population. Neurally adjusted ventilatory assist (NAVA) is a novel mode of ventilation that uses a functional naso/orogastric tube with embedded electrodes which detect diaphragmatic contractions (called the Edi signal). NAVA uses this Edi signal to synchronize ventilator support to the patient's own respiratory efforts and to support these efforts as needed. Few studies have examined the use of NAVA with non-invasive ventilation (NIV) in preterm neonates. A group at Arkansas Children's Hospital recently completed a study, looking at work of breathing in an animal model comparing NIV NAVA with the unsynchronized nasal intermittent positive pressure (NIPPV) mode currently used at this hospital. They were able to show that work of breathing was lower with NAVA in this model. This study will take what was shown in the animal model and translate this to the bedside. Using respiratory inductance plethysmography to measure thoracoabdominal asynchrony, this study will compare work of breathing during NIPPV versus NIV NAVA in preterm neonates with respiratory insufficiency. Hypothesis: Work of breathing as estimated by the phase angle (θ) using respiratory inductance plethysmography will be decreased with the use of NIV NAVA in comparison to unsynchronized NIPPV in premature neonates with respiratory insufficiency. Methods: Fifteen premature neonates of between 1-2 kilograms' current weight, with gestational age at birth between 24-34 weeks, and receiving non-invasive ventilation will be enrolled in the study after consent is obtained. The infants will be ventilated using NIV NAVA and NIPPV applied in random order for 15 minutes each while using respiratory inductance plethysmography to measure thoracoabdominal asynchrony as an estimate of work of breathing. Significance: This study will identify whether or not NIV NAVA has advantages over NIPPV for improving work of breathing in premature neonates.

Conditions

Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Phase angle (θ)

  The primary outcome of interest is phase angle (θ). Phase angle is reflective of work of breathing. Respiratory inductance plethysmography (RIP) signals will be analyzed as sine waves of the same frequency for the phase angle as follows: θ = (δt/P) x 360 degrees, where δt represents the time shift between the two sine waves and P is the wave period or cycle time.

  30 minutes

Secondary Outcomes (10)

• Tidal volume (arbitrary units, AU)

  30 minutes

• Minute ventilation (AU/min)

  30 minutes

• Respiratory rate (breaths/min)

  30 minutes

• Transcutaneous oxygen (mmHg)

  30 minutes

• Transcutaneous carbon dioxide (mmHg)

  30 minutes

Study Arms (2)

NIV NAVA then NIPPV

OTHER

Infants will receive 15 minute trials of noninvasive neurally adjusted ventilatory assist (NIV NAVA) and nasal intermittent positive pressure ventilation (NIPPV) in random order with the first 10 minutes after changing to be considered a washout period and the last 5 minutes used for data collection. This group will receive NIV NAVA then NIPPV.

Other: Noninvasive neurally adjusted ventilatory assist (NIV NAVA); Other: Nasal intermittent positive pressure ventilation (NIPPV)

NIPPV then NIV NAVA

OTHER

Infants will receive 15 minute trials of noninvasive neurally adjusted ventilatory assist (NIV NAVA) and nasal intermittent positive pressure ventilation (NIPPV) in random order with the first 10 minutes after changing to be considered a washout period and the last 5 minutes used for data collection. This group will receive NIPPV then NIV NAVA.

Other: Noninvasive neurally adjusted ventilatory assist (NIV NAVA); Other: Nasal intermittent positive pressure ventilation (NIPPV)

Interventions

Noninvasive neurally adjusted ventilatory assist (NIV NAVA) OTHER

Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation that uses a functional naso/orogastric tube with embedded electrodes which detect diaphragmatic contractions (called the Edi signal). NAVA uses this Edi signal to synchronize ventilator support to the patient's own respiratory efforts and to support these efforts as needed.

NIPPV then NIV NAVA; NIV NAVA then NIPPV

Nasal intermittent positive pressure ventilation (NIPPV) OTHER

Nasal intermittent positive pressure ventilation (NIPPV) or noninvasive pressure control ventilation (NIV PC) is a mode of ventilation delivering unsynchronized puffs of air or "breaths" to a baby through nasal cannulae.

Also known as: Noninvasive pressure control ventilation (NIV PC)

NIPPV then NIV NAVA; NIV NAVA then NIPPV

Eligibility Criteria

• Age: Up to 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age at birth between 24 and 34 weeks
• Receiving noninvasive ventilation
• Between 1 and 2 kg current weight
• Current FiO2 requirement less than 0.40
• Clinical stability

You may not qualify if:

• Known major congenital anomalies (congenital heart disease, abdominal wall defects, gastrointestinal tract defects, cleft palate, or neurologic defects)
• Clinical instability (temperature instability, heart failure, bleeding, active infection, significant apnea or bradycardia)
• Known cystic fibrosis
• Use of inhaled nitric oxide
• Cyanotic congenital heart disease

Sponsors & Collaborators

• Arkansas Children's Hospital Research Institute: lead

Study Sites (1)

Arkansas Children's Hospital

Little Rock, Arkansas, 72205, United States

Location

Related Publications (13)

• Miller JD, Carlo WA. Pulmonary complications of mechanical ventilation in neonates. Clin Perinatol. 2008 Mar;35(1):273-81, x-xi. doi: 10.1016/j.clp.2007.11.004.

  PMID: 18280886 BACKGROUND

• Badiee Z, Nekooie B, Mohammadizadeh M. Noninvasive positive pressure ventilation or conventional mechanical ventilation for neonatal continuous positive airway pressure failure. Int J Prev Med. 2014 Aug;5(8):1045-53.

  PMID: 25489454 BACKGROUND

• Chang HY, Claure N, D'ugard C, Torres J, Nwajei P, Bancalari E. Effects of synchronization during nasal ventilation in clinically stable preterm infants. Pediatr Res. 2011 Jan;69(1):84-9. doi: 10.1203/PDR.0b013e3181ff6770.

  PMID: 20924313 BACKGROUND

• Vignaux L, Grazioli S, Piquilloud L, Bochaton N, Karam O, Levy-Jamet Y, Jaecklin T, Tourneux P, Jolliet P, Rimensberger PC. Patient-ventilator asynchrony during noninvasive pressure support ventilation and neurally adjusted ventilatory assist in infants and children. Pediatr Crit Care Med. 2013 Oct;14(8):e357-64. doi: 10.1097/PCC.0b013e3182917922.

  PMID: 23863816 BACKGROUND

• Sinderby C, Beck J. Neurally adjusted ventilatory assist in non-invasive ventilation. Minerva Anestesiol. 2013 Aug;79(8):915-25. Epub 2013 Apr 5.

  PMID: 23558763 BACKGROUND

• Stein H, Alosh H, Ethington P, White DB. Prospective crossover comparison between NAVA and pressure control ventilation in premature neonates less than 1500 grams. J Perinatol. 2013 Jun;33(6):452-6. doi: 10.1038/jp.2012.136. Epub 2012 Oct 25.

  PMID: 23100042 BACKGROUND

• de la Oliva P, Schuffelmann C, Gomez-Zamora A, Villar J, Kacmarek RM. Asynchrony, neural drive, ventilatory variability and COMFORT: NAVA versus pressure support in pediatric patients. A non-randomized cross-over trial. Intensive Care Med. 2012 May;38(5):838-46. doi: 10.1007/s00134-012-2535-y. Epub 2012 Apr 6.

  PMID: 22481227 BACKGROUND

• Beck J, Reilly M, Grasselli G, Mirabella L, Slutsky AS, Dunn MS, Sinderby C. Patient-ventilator interaction during neurally adjusted ventilatory assist in low birth weight infants. Pediatr Res. 2009 Jun;65(6):663-8. doi: 10.1203/PDR.0b013e31819e72ab.

  PMID: 19218884 BACKGROUND

• Lee J, Kim HS, Jung YH, Shin SH, Choi CW, Kim EK, Kim BI, Choi JH. Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. Arch Dis Child Fetal Neonatal Ed. 2015 Nov;100(6):F507-13. doi: 10.1136/archdischild-2014-308057. Epub 2015 Jul 15.

  PMID: 26178463 BACKGROUND

• Heulitt MJ, Clement KC, Holt SJ, Thurman TL, Jo CH. Neurally triggered breaths have reduced response time, work of breathing, and asynchrony compared with pneumatically triggered breaths in a recovering animal model of lung injury. Pediatr Crit Care Med. 2012 May;13(3):e195-203. doi: 10.1097/PCC.0b013e318238b40d.

  PMID: 22079957 BACKGROUND

• Clement KC, Thurman TL, Holt SJ, Heulitt MJ. Neurally triggered breaths reduce trigger delay and improve ventilator response times in ventilated infants with bronchiolitis. Intensive Care Med. 2011 Nov;37(11):1826-32. doi: 10.1007/s00134-011-2352-8. Epub 2011 Sep 23.

  PMID: 21946913 BACKGROUND

• Ulm LN, Hamvas A, Ferkol TW, Rodriguez OM, Cleveland CM, Linneman LA, Hoffmann JA, Sicard-Su MJ, Kemp JS. Sources of methodological variability in phase angles from respiratory inductance plethysmography in preterm infants. Ann Am Thorac Soc. 2014 Jun;11(5):753-60. doi: 10.1513/AnnalsATS.201310-363OC.

  PMID: 24716708 BACKGROUND

• Matlock DN, Bai S, Weisner MD, Comtois N, Beck J, Sinderby C, Courtney SE. Work of Breathing in Premature Neonates: Noninvasive Neurally-Adjusted Ventilatory Assist versus Noninvasive Ventilation. Respir Care. 2020 Jul;65(7):946-953. doi: 10.4187/respcare.07257. Epub 2020 Feb 18.

  PMID: 32071130 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ventilator-Induced Lung Injury; Lung Injury

Study Officials

• David N Matlock, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: June 2, 2016
• Study Start: August 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: January 11, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)