4 | DISCUSSION
In this study, a systematic review
of 13 RCTs demonstrated that the use of MISA techniques could
significantly reduce the incidence of BPD at 36 weeks, pneumothorax, and
hsPDA without increasing the incidence of other neonatal complications
compared with endotracheal intubation for surfactant delivery. MISA
techniques also reduced the need for mechanical ventilation within 72 h
of life or during hospitalization. Although MISA techniques increased
the rate of surfactant reflux, they did not increase the need for
additional surfactant, indicating that MISA techniques did not reduce
the efficiency of surfactant.
In addition, there was no significant difference in the mortality rate
between the two groups. On the one hand, the mortality rate was lower in
the MISA group than that in the control group (9.1% vs. 12.1%), and it
was right on the edge of statistical significance (p = .05), so further
analysis is needed after additional RCT studies are published. On the
other hand, the mortality rate was significantly reduced in the MISA
group after sensitivity analysis (RR = 0.69, 95% CI : 0.51 to 0.95, p =
.02). This reduction might have been due to the younger gestational age
of subjects in the excluded study (gestational age, < 29
weeks) 14,19. The younger the gestational age, the
higher the mortality rate 27,28. The effect of
gestational age on mortality was greater than that of surfactant
delivery techniques between the two groups. Overall, the results
concluded here were robust to most sensitivity analyses.
Pneumothorax occurred less frequently in the MISA group than in the
control group, considering that MISA techniques do not cause pressure or
volume damage from brief mechanical ventilation. Similarly, the
incidence of hsPDA in the MISA group was lower than that in the control
group, suggesting that MISA techniques had fewer effects on
hemodynamics. Epidemiological studies have reported that hsPDA
associates with BPD 29. hsPDA increased the pressure
of pulmonary capillary bed arteries and veins, resulting in more fluid
infiltration into the pulmonary interstitium, which aggravated pulmonary
edema. In this study, the incidence of hsPDA in the MISA group was lower
than that in the control group, which might have been another reason for
the low incidence of BPD.
The use of INSURE techniques for surfactant delivery has been widely
reported in clinical practice, but many shortcomings remain30,31. Surfactant delivery in a noninvasive approach
that reduces the hazards of endotracheal intubation, and it includes
aerosolized administration 32, laryngeal mask
airway–guided administration 33,34, pharyngeal
administration 35, and minimally invasive pulmonary
surfactant administration. However, due to the lack of relevant studies
on the first three approaches, the results are inconsistent, and further
studies are needed to evaluate their safety and effectiveness36,37. Compared with endotracheal intubation, the
possible advantages of minimally invasive administration are as follows.
Firstly, thin tubes can reduce damage to vocal cords and the tracheal
mucosa 9. Secondly, MISA techniques can prevent lung
injury in premature infants from high pressure or lung overdistension10,38. Finally, they allow uninterrupted application
of NCPAP during surgery, thereby facilitating the maintenance of stable
oxygen saturation 39.
This meta-analysis searched for RCT studies using a thin catheter for
surfactant delivery and included LISA and MIST techniques, leading to
differences from other meta-analyses. A previously published
meta-narrative review failed to identify a lesser BPD at 36 weeks in the
MISA group 40, but this study observed a reduction in
BPD at 36 weeks, which was consistent with the conclusions of a mesh
meta-analysis and a cross-sectional observational multicenter study41,42. In comparison with a recent meta-analysis43, after excluding the same two RCTs for sensitivity
analysis, this study found a reduction in mortality, whereas the authors
of the previously published meta-analysis did not.
Although we strived for a comprehensive and accurate meta-analysis,
there were several limitations. First, there were differences in the
gestational age and the body weight among the studies, and lung tissues
at different stages of development showed different sensitivities to
injury from mechanical ventilation, which might have affected the
incidence of BPD at 36 weeks, pneumothorax, and other complications.
Second, different doses and types of surfactant might have affected the
outcome of the study. Due to the limited number of existing studies, it
was difficult to evaluate the aforementioned factors in the groups, and
additional large-sample, multi-center clinical studies are needed to
further explore the efficacy and safety. Finally, none of the included
studies reported long-term neurodevelopmental follow-up data.
In conclusion, the use of MISA techniques for surfactant delivery not
only reduced the need for mechanical ventilation (within 72 h of life or
during hospitalization), but also reduced the incidence of BPD at 36
weeks, pneumothorax, and hsPDA without increasing the incidence of other
complications. Therefore, MISA techniques should be considered as part
of the lung protective strategy for premature infants with NRDS.
However, the specifics of these techniques are rarely reported and
related large-sample multicenter studies are scarce. Therefore,
additional well-designed, well-targeted RCT studies are needed to
evaluate their efficacy and safety.
A CKNOWLEDGEMENT
We thank International Science Editing (
http://www.internationalscienceediting.com ) for editing this
manuscript.
CONFLICT OF INTERESTS
The
authors have no conflicts of interest to declare.
AUTHOR CONTRIBUTIONS
Xiaohong Wu and Zhoushan Feng conceptualized and designed research,
collected and analyzed data, and drafted this article. Yiyu Lai and Juan
Kong analyzed the data, reviewed the data, and revised the draft.
Chunhong Jia and Zhanyuan Xu participated in design research, collecting
and analyzing data. Yaoyong Chen, Qiliang Cui and Fan Wu supervised the
elaboration of the research design, data analysis, and reviewed the
manuscript. All authors have approved the final version of this article.