NASONE Trial and NIPPV: Evidence-Based Recommendations
Direct Answer Based on NASONE Trial Evidence
The NASONE trial demonstrated that noninvasive high-frequency oscillatory ventilation (NHFOV) and nasal intermittent positive pressure ventilation (NIPPV) are both superior to nasal continuous positive airway pressure (NCPAP) in reducing reintubation rates and duration of invasive mechanical ventilation in preterm neonates, with NHFOV showing additional benefits in reducing moderate-to-severe bronchopulmonary dysplasia. 1
Key NASONE Trial Findings
Primary Outcomes in High-Risk Subgroups
The NASONE trial specifically evaluated three predefined high-risk populations and found consistent benefits across all groups 1:
Extremely preterm infants (≤28 weeks' gestation): Both NIPPV and NHFOV reduced reintubation risk by 15-28% compared to NCPAP (number needed to treat: 3-7 infants) 1
Infants ventilated >1 week from birth: Similar reductions in reintubation rates with NIPPV and NHFOV versus NCPAP 1
Infants with severe respiratory failure (CO₂ >50 mmHg): Both interventions significantly reduced early reintubations (risk difference: -20% to -24%) 1
Duration of Mechanical Ventilation
NIPPV and NHFOV shortened invasive mechanical ventilation duration by 2.3 to 5.0 days compared to NCPAP across all high-risk subgroups 1
Bronchopulmonary Dysplasia Reduction
NHFOV specifically reduced moderate-to-severe bronchopulmonary dysplasia by 10-12% compared to NCPAP (number needed to treat: 8-9 infants), which was not observed with NIPPV 1
Clinical Application Algorithm
Patient Selection Criteria
Eligible candidates for NIPPV/NHFOV based on NASONE trial:
- Preterm neonates requiring first extubation in NICU 1
- Gestational age ≤28 weeks (extremely preterm) 1
- Previous invasive ventilation >1 week from birth 1
- CO₂ levels >50 mmHg before or within 24 hours after extubation 1
Device and Mode Selection
Ventilator-generated NIPPV is superior to bilevel devices for reducing respiratory failure post-extubation (risk ratio 0.49 vs 0.95 for bilevel devices) 2, 3
NHFOV and NIPPV are equally effective in reducing IMV duration and reintubation rates, with no significant interaction effect between interventions 1
Pressure Settings
The NASONE trial protocol specified higher mean airway pressure in NHFOV than NIPPV, and higher in NIPPV than NCPAP, which is critical for efficacy 1
Safety Profile
Equivalent Safety Across Interventions
All three interventions (NCPAP, NIPPV, NHFOV) were equally safe in the NASONE trial despite different mean airway pressures 1
Gastrointestinal Complications
NIPPV likely results in little to no difference in gastrointestinal perforation compared to NCPAP (risk ratio 0.89,95% CI 0.58 to 1.38) 2
Necrotizing enterocolitis rates are similar between NIPPV and NCPAP (risk ratio 0.86,95% CI 0.65 to 1.15) 2
Contraindications and Monitoring Requirements
Absolute Contraindications
NIPPV should not be used in patients with 4:
- Recent facial or upper airway surgery
- Facial burns or trauma
- Fixed upper airway obstruction
- Active vomiting
Relative Contraindications Requiring ICU Monitoring
NIPPV can be used with contingency plans for intubation in 4:
- Recent upper gastrointestinal surgery
- Inability to protect airway
- Copious respiratory secretions
- Life-threatening hypoxemia
- Severe co-morbidity
- Confusion/agitation
- Bowel obstruction
Essential Monitoring Parameters
Patients must be alert with adequate spontaneous respiratory effort for NIPPV to be effective 4
Continuous monitoring in HDU/ICU setting is required for patients who would be candidates for intubation if NIPPV fails 4
Trial duration should be limited to 1-2 hours before proceeding to intubation if no improvement occurs 4
Critical Implementation Pitfalls
Avoid Premature Application
Do not use NIPPV preventively in normocapneic patients - a multicenter trial showed significantly decreased survival when NIPPV was used preventively (FVC 20-50% predicted, normocapneic) in Duchenne muscular dystrophy patients 4
Ensure Adequate Ventilatory Support
Contradictory results in COPD trials likely resulted from inadequate ventilation levels, insufficient adjustment time, and inappropriate patient selection 5
Device-Specific Considerations
BiPAP ventilators are simpler, cheaper, and more flexible than other ventilator types, and were used in the majority of randomized controlled trials 6
Terminology for ventilation modes varies significantly between manufacturers, potentially causing clinical confusion 6
Outcomes Not Affected by NIPPV
NIPPV likely results in little to no difference in 2:
- Chronic lung disease at 36 weeks (risk ratio 0.93,95% CI 0.84 to 1.05)
- Mortality prior to discharge (risk ratio 0.81,95% CI 0.61 to 1.07)