Two Noninvasive Ventilation Modes Win for Riskiest NICU Newborns

The known advantages of certain noninvasive respiratory support techniques prevailed for extremely preterm newborns following extubation and for those with more severe respiratory failure, subgroup analyses of the NASONE trial found.

Use of unsynchronized noninvasive intermittent positive pressure ventilation (NIPPV) or noninvasive high-frequency oscillatory ventilation (NHFOV) was associated with 15% to 28% fewer reintubations compared with nasal continuous positive airway pressure (NCPAP) across subgroups of interest. The number needed to treat to prevent one reintubation ranged from three to seven infants.

Additionally, both NIPPV and NHFOV treatments were also associated with significantly fewer early intubations in particular. The instances of early reintubation that did occur with NIPPV and NHFOV treatment were less often the result of refractory hypoxemia, reported Zhichun Feng, MD, of the Seventh Medical Center at Chinese PLA General Hospital in Beijing, and coauthors.

“These results confirm the main NASONE trial results and help [in] tailoring the respiratory support strategy to extremely preterm or severely ill infants,” the authors wrote in JAMA Network Open.

They added that the NIPPV and NHFOV groups spent fewer days on intensive mechanical ventilation (IMV) than the NCPAP group. Infants in the NHFOV treatment group in particular also had significantly less moderate-to-severe bronchopulmonary dysplasia (BPD), for a number needed to treat eight to nine infants across subgroups.

Notably, that reduction in moderate-to-severe BPD may be attributed to the physiology-based ventilatory approach of the NASONE trial, they said, which permits higher airway pressure and alveolar recruitment maneuvers allowed in the NHFOV group.

Feng and colleagues ultimately stated that while these findings suggest that NIPPV or NHFOV are better treatment options than NCPAP, it is important to use discretion and understand the unique situation of the studied subgroups.

“Because there are several respiratory techniques available, it is clear that there is no single solution for all patients. Conversely, we can consider that NIPPV and NHFOV are essentially similar, and better than NCPAP, in terms of reintubation and total duration of IMV during the whole NICU [neonatal intensive care unit] stay,” they suggested.

“The results, notably those regarding moderate-to-severe BPD (which was only a secondary outcome), should be confirmed in specifically designed trials,” they added.

The NASONE study was conducted at 69 NICU locations in China from December 2017 to May 2021. Patients were randomized to the type of treatment they would receive (NIPPV, NHFOV, or NCPAP) “when extubation was imminent,” and remained in their study group from the time they were extubated to the time they were discharged. In instances of reintubation and subsequent re-extubation, the same treatment method was used on an individual patient.

The primary analysis of the trial showed that both NHFOV and NIPPV carried a lower risk of reintubation than NCPAP in a wider cohort of babies born preterm (N=1,440). Furthermore, NHFOV slightly reduced the duration of IMV.

A total of 1,137 preterm infants were included in the present secondary analysis of the trial. Boys made up more than half of each predefined subgroup of neonates:

• Born at 28 weeks gestation or earlier (n=455)
• Receiving IMV for longer than 1 week following birth (n=375)
• Having a CO₂ level above 50 mm Hg either before or during the first 24 hours following extubation (n=307)

Among the limitations to the study include reduced power in subgroup comparisons, potential center effect impact, and possible influence by concurrent factors such as extrapulmonary prematurity-related complications, according to Feng’s group.

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