Discussion
This meta-analysis of 23 trials with 2,924 participants compared the respiratory support for neonates using NHFOV and NIPPV. The results showed that compared with NIPPV, NHFOV reduced the intubation rate in the initial respiratory support and the reintubation rate without time limit in the post-extubation respiratory support. While the rate of reintubation within 7days and 72h were similar. NHFOV decreased the duration of non-invasive ventilation, in post-extubation respiratory support, and no difference between the two ventilation modes was observed in the initial respiratory support. Newborns’ LOS was also decreased with NHFOV, although a significant difference was found only in post-extubation respiratory support in premature infants with respiratory failure (28–34 weeks of gestation, < 2,000 g birth weight) (26). Finally, NHOFV reduced PaCO2 levels and enhanced PaO2 levels and the SpO2/FiO2 ratio at 1 h and 24 h after non-invasive respiratory support. The risk of BPD, apnea and abdominal distention was reduced by NHFOV, but not NIPPV. However, the results should be interpreted with caution because of the significant heterogeneity among the included studies, the high sensitivity observed in the analysis of the reintubation rate without time limit and within 72 h, and the asymmetric funnel plot of the duration of non-invasive ventilation and the NEC incidence.
Complications caused by IMV seriously affect the long-term quality of life of newborns and increase an already large burden on their families. Avoidance of endotracheal intubation and IMV has become a goal of neonatal physicians. We found that NHFOV significantly reduced intubation rates during initial respiratory support, unlike NIPPV. This difference can be explained partly by the ability of NHFOV to improve alveolar ventilation and promote carbon dioxide excretion (31). The superiority of NHFOV over NIPPV, in terms of CO2 clearance efficacy has been demonstrated. After 1 h and 24 h of non-invasive respiratory support, NHOFV significantly reduced PaCO2 levels unlike NIPPV. However, the reintubation rate in post-extubation respiratory support should be viewed with caution. Our study showed that NHFOV reduced the reintubation rate without time limit, but this was not robust in the sensitivity analysis. Efficacious clearance of PaCO2 is only one of several factors that might help prevent extubation failure. The pre-extubation mean airway pressure (MAP), FiO2 and tidal volume also influenced the success of extubation. Unfortunately, the mechanical ventilation parameters before extubation were not detailed in the included studies. In very low-birth weight preterm infants (< 1,500 g), NHFOV influenced post-extubation respiratory support. The study by Z. Wang et al. (28) of preterm very low birthweight infants treated with NHFOV versus NIPPV reported that NHFOV reduced the reintubation rate within 72 h of extubation. The Y. Li et al. study of preterm infants (16) also found that NHFOV had a lower reintubation rate within 7 days of extubation, unlike NCPAP and NIPPV. Unfortunately, we did not conduct a subgroup analysis based on gestational age or birth weight, which is one of the study’s limitations.
In terms of adverse outcomes, NHFOV significantly reduced the risk of BPD, compared with NIPPV. Attenuation of intra-tracheal pressure with NHFOV lowered alveolar pressure, thereby maintaining the end-expiratory volume at a normal level without atelectatic trauma to the lung parenchyma, thus reducing the risk for BPD (33). The shorter duration of non-invasive ventilation observed in the NHFOV group might have contributed to the reduction in BPD. Moreover, NHFOV does not induce glottal constrictor muscle activity, in contrast to NCPAP, thereby obtaining sufficient gas exchange and reducing the risk of apnea (34). Another study found that NHFOV significantly reduced the occurrence of apnea in newborns (35). Our study also showed that NHFOV reduced the incidence of apnea, while no significant differences were found in the subgroup analysis by study type or initial or post-extubation respiratory support. Therefore, the benefits of NHFOV for apnea require further study. No increase in serious adverse outcomes (air leaks, NEC, IVH, nasal injury, ROP, PNX and periventricular leukomalacia) was observed in our study.
This meta-analysis has several limitations: the analyzed trials differed in their study designs and participants’ clinical characteristics. The causes of respiratory distress were heterogeneous among the participants; however, we were unable to conduct subgroup analyses of the different causes due to the lack of patient data. Finally, no standardized instruments are available to assess intubation risk and IMV across countries.