Nasal HFOV Versus Nasal SIPPV in Neonate Following Extubation: RCT Crossover Study

Study Overview
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Brief Summary
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Mechanical ventilation was introduced to treat respiratory failure in preterm infants or sick neonates then improvements in survival (1,2). However, the complications from short or long term use of ventilation can result in unintended harm or burden (e.g., air leak syndrome, pneumonia, bronchopulmonary dysplasia, neurological injury, retinopathy of prematurity) (3,4). To reduce these risks, clinicians should aggressive extubated neonates as early as possible. Respiratory (focus on blood gas as well as partial pressure CO2 [pCO2]) or extubation (focus on clinical condition as well as reintubation) failure was worrisome in pediatrician and parents if the neonate was reintubated owing to complete recovery of lung disease or inadequate respiratory drive. Non-invasive ventilation (NIV) was supported for primary respiratory support (initial mode before endotracheal intubation) or post-extubation. Nasal continuous positive airway pressure (nCPAP) was familiar to NIV mode in neonatal respiratory support. Nowadays, the new NIV modalities are nasal intermittent synchronized positive pressure ventilation (nSIPPV) and nasal high frequency oscillation (nHFO). To increase the likelihood of nCPAP success, other new modalities of NIV may be interesting. From theory, nSIPPV and nHFO combines peak inspiratory pressure (PIP) with synchrony and high-frequency oscillations without synchrony above CPAP, respectively. From meta-analysis, nSIPPV and nHFO were statistically significant superior than nCPAP both respiratory and extubation failure in neonate (5,6). The aim of our study was to investigate the efficacy of nHFOV and nSIPPV for CO2 clearance and reintubation rate after extubated neonates. The investigators hypothesized that nHFOV mode would improve CO2 clearance better than nSIPPV mode.

Detailed Description
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The primary outcome (pCO2) was measured by crossover RCT. The secondary outcome (reintubation within 7 days) was measured by paralleled RCT.

Official Title
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Nasal High Frequency Oscillatory Versus Synchronized Intermittent Positive Pressure Ventilation in Neonate Following Extubation: Randomized Controlled Crossover Study

Conditions
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High-Frequency Ventilation, Intermittent Positive-Pressure Ventilation, Newborn Morbidity, Noninvasive Ventilation

Intervention / Treatment
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* Device: Non-invasive ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born in hospital and admit in NICU The first endotracheal intubation and need NIV if extubation Umbilical arterial catheterization to draw the blood gas Neonate has not been intervened from another RCT study Exclusion Criteria: Major congenital anomalies or chromosomal abnormalities Neuromuscular diseases Upper respiratory tract abnormalities Suspected congenital lung diseases or pulmonary hypoplasia Need for surgery known before the first extubation Grade IV intraventricular hemorrhage occurring before the first extubation Palliative care Parents' decision not to participate

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized Controlled Crossover Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nasal high frequency oscillatory ventilation<br>nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = MAP (before extubation) + 2 or 8 (preterm), 10 (term) cmH2O, dP = 2-3 times of MAP with visible chest oscillations or 25-35 cmH2O, I:E = 1:1, FiO2 = FiO2 (before extubation) + 0.1-0.2 keep targeted SpO2 90-94% | Device: Non-invasive ventilation<br>* Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher & Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow > 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)<br>|
| Experimental: nasal synchronized intermittent positive pressure ventilation<br>nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = PIP (before extubation) + 2-5 or 20 (preterm), 25 (term) cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = FiO2 (before extubation) + 0.1-0.2 keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected. | Device: Non-invasive ventilation<br>* Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher & Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow > 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| partial pressure CO2 (pCO2) | After randomization, the initial non-invasive ventilation (NIV) was started then blood gas was obtained after 2 hours. The participant was switched to another NIV and blood gas was obtained after 2 hours. | 4 hours after NIV start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| extubation failure | The participant was continued with the last NIV mode until the NIV was stopped. The participant was excluded if severe respiratory failure with reintubation during 4 hours after intervention. Extubation failure will be defined by reintubation after NIV mode. | 7 days after extubation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Failure, Nasal High-Frequency Oscillation, Nasal Synchronized Intermittent Positive Pressure, Extubation Failure