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.