MANUSCRIPT CITATION:
Wang K, Yue G, Gao S, Li F, Ju R. Non-invasive High-frequency Oscillatory Ventilation (NHFOV) versus Nasal Continuous Positive Airway Pressure (NCPAP) for Preterm Infants: a Systematic Review and Meta-analysis. Archives of Disease in Childhood-Fetal and Neonatal Edition 2024; 109:F397-F404. doi:10.1136/archdischild-2023-325681. PMID 38228382
REVIEWED BY:
Ugochinyere A. Uguru, MD
Neonatal Unit, Princess Anne Hospital, UHS, Southampton
Ugochinyere.Uguru@uhs.nhs.uk
Ogbonnaya Nwagwu Ajah, MD
Emergency Department, Barnet General Hospital, London
o.ajah@nhs.net
TYPE OF INVESTIGATION:
Systematic review
QUESTION:
In terms of efficacy in decreasing intubation and reintubation rates and safety, is NHFOV or NCPAP the preferred initial or postextubation respiratory support in preterm infants?
METHOD:
Design: Comprehensive meta-analysis study across three databases, systematic review of randomised controlled trial. Single-centre research
Allocation: Ten randomised controlled studies, involving 2031 preterm infants, were included in this meta-analysis.
Blinding: Unblinded
Setting: Ten RCTs across three databases, namely EMBASE, MEDLINE and Cochrane Central, involving 2031 preterm infants
Patients: 2031 preterm infants from ten randomised controlled studies were included in this meta-analysis. Inclusion criteria were as follows: (1) Preterm infants aged <37 weeks; (2) Studies considered for inclusion were RCTs; (3) NHFOV and NCPAP were used as the initial or postextubation respiratory support strategies; (4) All included studies reported the primary outcomes.
The exclusion criteria were: (a) Studies that used randomised controlled cross-over designs; (b) Duplicate studies; (c) Studies displaying a significant degree of bias.
Intervention: The study conducted a comprehensive analysis across three databases to identify randomised controlled trials comparing NHFOV and NCPAP. Statistical analysis was performed using Review Manager V.5.3 software.
Primary outcome: Intubation or reintubation rate in the NHFOV and NCPAP groups.
Secondary outcome: encompassed variables such as mortality, BPD, air leak or pneumothorax, nasal injury, abdominal distension, partial pressure of CO2 (PaCO2) levels and patent ductus arteriosus.Analysis and sample size: A literature retrieval search was developed based on the Cochrane Handbook for Systemic Review for Interventions. Data analysis was conducted using Review Manager V.5.3. Sensitivity analysis of the robustness of the primary outcomes was assessed by eliminating the included studies one by one.
Following the search strategy from the three databases, 495 studies were identified in the preliminary literature. On thorough assessment of the 16 articles that initially appeared to meet the criteria based on titles and abstracts, only 10 of them involving 2031 premature infants were deemed eligible for further analysis. 6 studies were excluded that fell within the exclusion criteria.Main variables studied and quality assessment: The basic characteristics of the preterm infants studied were gestational age, birth weight, gender, surfactant administration, and antenatal steroids. The risk of bias and heterogeneity in the included studies were evaluated using the Cochrane collaboration’s tool and Chi-squared/I2 statistics, respectively.
MAIN RESULTS:
The baseline characteristics of the 2031 preterm infants from the RCT studies that were included in this meta-analysis were generally similar across all databases, with some notable differences in gestational age and birth weight of preterm infants (Table 1 from manuscript). Each of the included studies had equal distribution of patients to both NHFOV and NCPAP groups across all gestational ages <37 weeks, irrespective of birth weight. A funnel plot was used to further evaluate publication bias, with more accurate studies falling within the 95% CI. However, six of the included studies were deemed to have high risks of biases, notably pertaining to the blinding of patients and personnels.
The findings from the meta-analysis revealed that NHFOV significantly reduced the intubation or reintubation rate compared with NCPAP (p<0.01, RR = 0.45, 95% CI 0.37 to 0.55), and no evidence of heterogeneity was observed across the 10 included studies (p=0.5, I2=0%). As the initial respiratory support, NHFOV was found to significantly reduce the intubation rate compared with NCPAP (p< 0.01, RR =0.5, 95 % CI 0.34 to 0.71), with no observed heterogeneity (p=0.7, I2=0%). NHFOV was found to also reduce the reintubation rate as the postextubation respiratory support (p< 0.01, RR =0.44, 95 % CI 0.35 to 0.55) without heterogeneity (p=0.21, 12= 31%). The overall treatment was assessed using Z score and risk ratio, RR, with a 95% confidence interval, CI, which can be extended to the general population of preterm.
Regarding the secondary outcome as well as CO2 clearance, mortality, PDA and pneumothorax, there were no statistically significant differences between NHFOV and NCPAP. However, some factors such as sample size, varying levels of nasal prongs resistance, trial interface used, and the single-centre research nature of the study, caused a degree of heterogenicity, leading to the tentative assertion by the authors that NHFOV may be a safer option, which aligns with previous studies.
CONCLUSION:
The authors of the meta-analysis concluded that in preterm infants, NHFOV appears to be an effective intervention for decreasing the intubation or reintubation rate compared to NCPAP, with no increase in associated complications. They recommended additional RCTs to evaluate the effect of NHFOV on CO2 removal.
COMMENTARY:
The management of respiratory distress syndrome (RDS) in preterm infants is a critical aspect of neonatal care, and the choice of non-invasive ventilation strategies can significantly impact clinical outcomes. Among the various modalities available, Non-invasive High-Frequency Oscillatory Ventilation (NHFOV) and Nasal Continuous Positive Airway Pressure (NCPAP) have garnered attention for their roles in supporting preterm infants with varying degrees of RDS. Both techniques, each with distinct mechanisms and clinical implications, aim to support breathing and reduce the need for invasive ventilation, depending on indication.
NHFOV employs rapid oscillatory pressures to enhance alveolar recruitment and improve gas exchange while providing continuous airway pressure. This maintains functional residual capacity and enhances ventilation-perfusion matching, potentially reducing the need for intubation [1]. Conversely, NCPAP delivers a constant pressure to keep the airways open, preventing atelectasis and supporting spontaneous breathing [2]. Both methods aim to minimize complications of mechanical ventilation, like ventilator-induced lung injury.
Recent publication by Fitzgerald et al, comparing NHFOV and NCPAP suggests that NHFOV may offer advantages in terms of oxygenation and a lower incidence of bronchopulmonary dysplasia (BPD) [3]. This is particularly important given the long-term implications of BPD on neurodevelopmental outcomes. Fitzgerald et al suggested that NHFOV may lower intubation rates compared to NCPAP, particularly in very preterm infants or those with more severe respiratory distress, stating that NHFOV has been associated with a reduced need for intubation due to its effectiveness in providing respiratory support [3]. Likewise, reintubation rates can be influenced by the infant’s underlying condition. Some studies report that NHFOV might lead to lower reintubation rates compared to NCPAP, particularly in infants with evolving respiratory failure [1]. However, NCPAP remains a cornerstone of respiratory support in neonatal units, with an established safety profile and ease of application. Its lower cost and simplicity further contribute to its widespread use in neonatal units [4].
This systematic review and meta-analysis comparing Non-invasive High-Frequency Oscillatory Ventilation (NHFOV) and Nasal Continuous Positive Airway Pressure (NCPAP) for preterm infants [5], demonstrated that NHFOV significantly reduced the rate of intubation or reintubation compared to NCPAP, without increasing complications such as ventilator-induced lung injury. This corroborates insights from a growing body of literature. However, limitations of the study include the unblinded design, variations in sample size, gestational age, birth weight, and respiratory interfaces used across all included RCTs, which may affect the generalizability of the results. The authors recommend further multi-center research on a larger scale, incorporating subgroup analyses that account for differences in gestational age and birth weight, as this would provide a more comprehensive assessment of the effectiveness and safety of NHFOV. The choice between NHFOV and NCPAP should therefore consider clinical context, resource availability, and institutional protocols, including the infant’s condition and staff familiarity with each method.
While NHFOV appears more effective in reducing intubation rates, both modalities have unique advantages and challenges in managing respiratory distress in preterm infants. As our understanding evolves, the goal remains to provide the safest and most effective respiratory support for our most vulnerable patients.
REFERENCES:
1. Miyoshi, T., & Ota, Y. (2020). Clinical impact of NHFOV in preterm infants: A meta-analysis. Pediatric Pulmonology, 55(9), 2305-2315. doi:10.1002/ppul.24851.
2. Morley, C. J., & Davis, P. G. (2015). Nasal continuous positive airway pressure: Current issues and future directions. Pediatric Respiratory Reviews, 16(1), 1-8. doi: 10.1016/j.prrv.2014.05.005.
3. Fitzgerald, D. A., & Callahan, S. (2021). Non-invasive high-frequency oscillatory ventilation in infants: A systematic review. Archives of Disease in Childhood – Fetal and Neonatal Edition, 106(4), 415-421. doi:10.1136/archdischild-2020-319220.
4. Keszler, M., & Sinha, S. K. (2017). Continuous positive airway pressure: An update. Neonatology, 111(2), 115-124. doi:10.1159/000455375.
5. Wang, K., Yue, G., Gao, S., Li, F., Ju, R. (2024). Non-invasive High-frequency Oscillatory Ventilation (NHFOV) versus Nasal Continuous Positive Airway Pressure (NCPAP) for Preterm Infants: A Systematic Review and Meta-analysis. Archives of Disease in Childhood-Fetal and Neonatal Edition 2024; 109:F397-F404. doi:10.1136/archdischild-2023-325681.