A Pilot Study of Synchronized and Non-invasive Ventilation ("NeuroPAP") in Preterm Newborns (NeuroPAP)

There is currently a consensus that non-invasive ventilation (NIV) in preterm infants is preferred over intubation. There are two ways of delivering NIV in preterm infants, nasal continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV), where ventilator inflations are delivered intermittently over a fixed end-expiratory pressure. The synchronization in conventional mode is very difficult to obtain in premature infants. In all ventilation modes PEEP (end-expiratory pressure) is fixed. Considering that preterm infants are more likely to develop atelectasis, an active and ongoing management of the PEEP is very important to prevent de-recruitment.

A new respiratory support system (NeuroPAP) was developed to address these issues (synchronization problems and control the PEEP). It uses the electrical activity of the diaphragm (EDI) to control the ventilator assist continuously, both during inspiration (principle of NAVA mode) and also during expiration (based on tonic Edi level).

Study Overview

• Status: Completed
• Conditions: Respiratory Failure
• Intervention / Treatment: Device: NeuroBox to deliver the NeuroPAP

Detailed Description

The mode NeuroPAP will work with the continuous Edi-level and deliver pressures according to the Edi-signal x set NeuroPAP-level, over the whole breath (inspiration and expiration). The NeuroPAP will work between two pressure levels set by the user and named higher Pressure limit (Plimit) and minimum Pressure (Pmin).

A safety upper pressure limit (UPL) will also be set. A backup ventilation will be possible.

A specific gastric tube equipped with an array of microelectrodes (Edi catheter, Maquet, Solna, Sweden) will be installed after inclusion, by the same oral or nasal route as the tube previously in place. Patients will then be ventilated in the 5 aforementioned conditions:

• On conventional NIPPV device on clinical settings for a 30 minute period. The investigators will note the mean airway pressure being delivered with the clinical settings and the resulting peak Edi, as well as neural respiratory rate, tonic Edi, Fraction of inspired oxygen (FiO2), and Oxygen saturation by pulse oximetry (SpO2).
• With NeuroPAP without modification of Pmin (=peep). The exchange of the nasal interface may be necessary, depending on the original interface. FiO2 will initially be the same as previously set in conventional NIPPV. The Pmin will initially be set at the level of PEEP used during conventional NIPPV. A titration maneuver will be conducted to identify the optimal NeuroPAP level. The infant will be ventilated for one hour. Clinical adjustments in pressures and FiO2 are permitted. Safety termination will be established.
• NeuroPAP with adjusted Pmin: the Pmin in NeuroPAP will be reduced by 2 cm H2O, with the same NeuroPAP level. The patients will be ventilated for one hour.
• CPAP delivery with NeuroPAP device: the device will be switched to CPAP mode, for a 15 minute period
• A second 30 minutes period of the conventional NIPPV will be conducted.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • St. Justine's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterm infants, >26 0/7 and < 34 weeks GA, at least 3 days old and younger than 1 month,
• on NIPPV with settings in the range : Maximal inspiratory pressure (total, including PEEP) < 20 cmH2O, and PEEP : 5-7 cmH2O,
• with FiO2 <40%, and stable.

Exclusion Criteria:

• Suspected or proven pneumothorax
• Patient on high-flow nasal cannula or nasal continuous positive airway pressure (nCPAP)
• Infants with severe recurring apnea
• Recent worsening of respiratory status with increase work of breathing, recent increase in FiO2, or linked with a suspected sepsis
• Contraindications to the placement of a new nasogastric tube (e.g. severe coagulation disorder, malformation or recent surgery in cervical, nasopharyngeal or esophageal regions)
• Hemodynamic instability requiring inotropes.
• Severe respiratory instability requiring imminent intubation according to the attending physician, or FiO2 > 45%, or PaCO2 > 65 mmHg on blood gas in the last hour.
• Patient for whom a limitation of life support treatments is discussed or decided.
• Refusal by the treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NeuroBox to deliver the NeuroPAP

Device: NeuroBox to deliver the NeuroPAP; The patients will be studied during the following conditions: On conventional NIPPV device with the clinically prescribed settings (30 min); With NeuroPAP and no change of Pmin (=peep) (60 min); With NeuroPAP and adjusted Pmin (decreased by 2 cmH2O) (60 min); During CPAP delivered with NeuroPAP device (15 min); Again with original NIPPV device and settings for 30 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time effectively spent with NeuroPAP mode activated during the NeuroPAP period	Percentage	up to 30 minutes after reinstitution of the conventional NIPPV
Number of interruption of NeuroPAP during the NeuroPAP period	Number of interruption per patients	up to 30 minutes after reinstitution of the conventional NIPPV
Change in respiratory rates between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV
Change in cardiac rates between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV
Change in blood pressure between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV
Change in SpO2 between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV
Change in TcPCO2 between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent in asynchrony between standard NIV and NeuroPAP	% of time	up to 30 minutes after reinstitution of the conventional NIPPV
Change in trigger delays (ms) between standard NIV andNeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV
Change in non assisted breaths (wasted efforts) between standard NIV andNeuroPAP	% of change	up to 30 minutes after reinstitution of the conventional NIPPV
Change in autotriggered breaths between standard NIV and NeuroPAP	Percentage	up to 30 minutes after reinstitution of the conventional NIPPV
Change in Mean Airway pressure (cmH2O) between standard NIV and NeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV
Change in End expiratory pressure (PEEP, cmH2O) between standard NIV and NeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV
Change in Mean Electrical activity of diaphragm (Edi, mcV) between standard NIV and NeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV
Change in Peak Electrical activity of diaphragm (Edi, mcV) between standard NIV and NeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV
Change in Tonic Electrical activity of diaphragm (Edi, mcV) between standard NIV and NeuroPAP		up to 30 minutes after reinstitution of the conventional NIPPV

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Maquet Cardiovascular
• Investigators: Principal Investigator: Guillaume Emeriaud, MD, PhD, St. Justine's Hospital; Principal Investigator: Gregory Lodygensky, MD, PhD, St. Justine's Hospital; Principal Investigator: Jennifer Beck, PhD, Li Ka Shing Knowledge Institute. St. Michael's Hospital; Principal Investigator: Christer Sinderby, PhD, Li Ka Shing Knowledge Institute. St. Michael's Hospital

Publications and helpful links

General Publications

• Rochon ME, Lodygensky G, Tabone L, Essouri S, Morneau S, Sinderby C, Beck J, Emeriaud G. Continuous neurally adjusted ventilation: a feasibility study in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2020 Nov;105(6):640-645. doi: 10.1136/archdischild-2019-318660. Epub 2020 Apr 8.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): January 30, 2017
• Study Completion (Actual): January 30, 2017

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: January 30, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: CPAP; NIV; NIPPV; Edi
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: CHUSJ-4083