Next Article in Journal
Cerebral Amyloid Angiopathy: Clinical Presentation, Sequelae and Neuroimaging Features—An Update
Previous Article in Journal
The Impact of Urodynamic Findings on Fatigue and Depression in People with Multiple Sclerosis
Previous Article in Special Issue
Endoscopic Sinus Surgery Significantly Reduces Eustachian Tube Dysfunction Symptoms in Patients with Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Effectiveness of Humidified High Flow Nasal Cannula Versus Continuous Nasal Positive Airway Pressure in Managing Respiratory Failure in Preterm Infants: An Emergency Department Study

by
Duaa Yousof Mahboob
1,†,
Amber Hassan
2,3,4,*,†,
Faiza Naheed
5,
Arshad Ali Shah
6 and
Maria Fareed Siddiqui
5,*
1
Department of Emergency, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2
European School of Molecular Medicine, University of Milan, 20139 Milan, Italy
3
Laboratory of Translational Neuroscience, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy
4
Faculty of Allied Health Science, The University of Lahore, Lahore 54000, Pakistan
5
Faculty of Pharmacy, University of Lahore, Lahore 54000, Pakistan
6
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lahore, Lahore 54000, Pakistan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2025, 13(3), 602; https://doi.org/10.3390/biomedicines13030602
Submission received: 21 January 2025 / Revised: 14 February 2025 / Accepted: 24 February 2025 / Published: 1 March 2025

Abstract

:
Background: The HHFNC is routinely utilised as a non-invasive respiratory support for preterm infants with respiratory distress; few studies have compared it to nCPAP for the first treatment of respiratory distress in preterm neonates. This study aims to compare the effectiveness and outcomes of HHFNC and nCPAP in improving respiratory outcomes and reducing adverse effects. Methods: The 220 patients from the neonatal unit enrolled in the study (110 in each group) after obtaining written informed consent from their parents/guardians. Nasal CPAP was applied to patients in group A through a nasal mask with the following settings: FiO2: 40–60%, PEEP: 5–8 cm H2O, flow: 4–6 L/min. HHFNC was initiated at 5 L/min and adjusted between 3–7 L/min based on respiratory status, with FiO2 starting at 0.4 and modified to maintain SPO2; between 88–94%. Study variables were recorded and analysed using SPSS version 23.0. Results: The comparison of nCPAP (Group A) and HHFNC (Group B) showed no significant differences in age, gestational age, or clinical parameters, except for a higher respiratory rate in HHFNC. The HHFNC group had significantly shorter durations of non-invasive ventilator support and hospital stay. Adverse effects were more common in HHFNC, especially nasal mucosal injury, while sepsis was more frequent in nCPAP. Treatment failure occurred more often in the HHFNC group. Neonatal outcomes were similar, with no significant differences in discharge without the need for intubation rates, mortality, or intubation rates. Conclusions: The HHFNC is associated with a shorter duration of non-invasive ventilatory support and hospital stay compared to nCPAP. However, nCPAP demonstrated a significant survival advantage and a lower risk of treatment failure. Both modalities are effective in supporting preterm neonates with respiratory distress, but clinical considerations should guide the choice of therapy. Further research is necessary to confirm these findings and explore strategies to optimize outcomes and mitigate adverse effects associated with each modality.

1. Introduction

Respiratory distress syndrome (RDS) is a prevalent condition among preterm infants [1]. The use of non-invasive respiratory support (NRS) has been shown to lower the need for mechanical ventilation in these newborns [2]. Nasal continuous positive airway pressure (nCPAP) and heated humidified high-flow nasal cannula (HHHFNC) are widely used NRS strategies in neonatal intensive care units, offering comparable efficacy. However, their influence on feeding intolerance remains uncertain [3].
The nCPAP is the most popular non-invasive breathing assistance for preterm newborns, but it requires competent nursing care because of the bulky interfaces [4]. The HHFNC is a gentler option that is becoming popular among newborns and children with respiratory diseases [5].
The HHFNC are tiny, thin binasal prongs that supply oxygen or oxygen/air mixes at flow rates greater than 1 Litre per minute (L/min). They are located inside the nares and can take up to half of the available space without a seal [6]. Patients may tolerate larger flow rates since the gas is appropriately warmed and humidified when given. These high flow rates can equal or surpass patients’ inspiratory flow rates, limiting room air intake while ensuring that the percentage of oxygen (FiO2) inspired by patients matches the FiO2 given by the HHFNC system. The HHFNC approach is increasingly being employed for non-invasive respiratory support in preterm newborns, critically sick children, and adults [7].
The use of HHFNC in neonatal intensive care units (NI-CUs) in developed countries has significantly increased over the past six years [8]. This is owing to its effectiveness, safety, and perceived advantages over nCPAP, such as a simpler, smaller nasal interface and more comfort for babies [9,10]. Literature supports that HHFNC can avoid extubation failure, improve respiratory function, and aid in weaning off nCPAP [11]. Another study found that nasal cannulae flows of up to 2.5 L/min are equally effective as nasal nCPAP for treating apnoea of prematurity without raising oxygen requirements [12].
The studies have thoroughly examined HHFNC and nCPAP for the therapy of respiratory failure in preterm infants, emphasising their efficacy and related consequences [13,14]. This study aims to compare both treatment modalities, focusing on the mean duration of hospital stay and the mean duration of dependency on respiratory support, the ease of administration, improved compliance, and better patient outcomes compared to traditional ventilation methods.

2. Materials and Methods

2.1. Study Design and Patient Enrolment

The quasi-experimental study Reference No: (247-23) was conducted after ethical approval in 2023 from the Research Ethics Committee (REC) (IRB-SPRM/2023-24-I) in the University of Lahore Teaching Hospital, Lahore, Pakistan, and consent was taken from the parent/guardian. Patients were enrolled from the Neonatal Unit at the University of Lahore Teaching Hospital, Lahore, Pakistan. Non-probability, consecutive sampling was used to add 220 (110 in each group) patients to the study. The sample size, calculated by using the power of the study equal to 80% and a level of significance equal to 5%, taking treatment failure in the HHFNC group as 38.1% and in nCPAP as 20.9%, was 220 (110 in each group) patients [15].

2.2. Patient Selection and Grouping

All preterm neonates born between 32 and 34 weeks of gestation and aged 1 to 28 days, who experienced type 1 respiratory failure and needed non-invasive ventilator support, such as HHFNC or nCPAP, were enrolled in the study. We excluded patients with congenital heart disease or neuromuscular abnormalities, as well as newborns who experienced type 2 respiratory failure or required invasive mechanical ventilation or intubation.

2.3. Training Session

The Training session was arranged by the principal researcher for fellow doctors and nurses of the neonatal unit in which they were given detailed training regarding data collection, procedures, and interventions used in this study.

2.4. Data Collection

Written and informed consent was taken from parents/legal guardians for each patient after explaining the procedure and complications. The patient’s history, including gestational age, was noted. Diagnosis of respiratory failure was established with the help of clinical findings, radiological findings, and arterial blood gas analysis. Baseline variables pH, PaCO2, and PaO2 were noted by arterial blood gases. The respiratory rate was recorded. The nCPAP was applied to group 1 through a nasal mask with the following settings: FiO2: 40–60%, PEEP: 5–8 cm H2O, Flow: 4–6 L/min. HHFNC was applied to group 2 through the nasal cannula with the following settings: FiO2: 40–60%, Flow: 4–6 L/min. Infants receiving HHFNC therapy were initially started on a flow rate of 5 L/min, which was then adjusted between 3 and 7 L/min based on their respiratory status to maintain blood gas parameters within normal ranges. The fraction of inspired oxygen (FiO2) was set at 0.4 at the start of therapy and subsequently modified to ensure that oxygen saturation (SpO2) remained within the target range of 88–94%.
Data was recorded about the duration of hospital stay in days & duration of application of respiratory support, i.e., nCPAP or HHFNC at the time of discharge. Arterial Blood Gases were performed daily or as per the requirement to check the PO2 and PCO2. Vitals were recorded on an hourly basis, and any change of nCPAP & HHFNC settings were recorded. The same Antibiotics [Cefotaxime 150 mg/kg/24 h (Bosch Pharmaceuticals (Pvt) Ltd.; Karachi; Pakistan) & Ampicillin 200 mg/kg/24 h (Bosch Pharmaceuticals (Pvt) Ltd.; Karachi; Pakistan) as 1st line] and other treatments, including maintenance fluid, were given to both groups as per requirement. All the data was recorded on a pre-designed proforma by the staff members and results were subjected to statistical analysis by the principal researcher to determine the significance of observed differences. The data collection continued until the enrolled neonates were discharged from the hospital.
The data collection aimed to analyse the following outcomes; total duration of hospital stay in days, mean duration of application of respiratory support in hours, frequency of adverse events including sepsis (identified based on clinical symptoms, positive blood culture, and elevated inflammatory markers such as CRP), frequency of nasal mucosal injury, abdominal distension, feeding intolerance, outcome (discharged, expired, intubated and treatment failure) and neonatal outcomes (discharge, expired, intubated).

2.5. Data Analysis

Collected data was entered and analysed using Statistical Package for Social Science (SPSS) version 23.0. All the quantitative variables like age, APGAR score, gestational age of mother, duration of hospital, respiratory support, and total days of oxygen use up to the time of discharge for each group were reported by Mean ± SD. All the qualitative variables like gender, neonatal outcomes (discharge, expired, intubated), adverse events like sepsis, abdominal distention, feeding intolerance, and nasal mucosal injury) and outcome (discharged, expired, intubated, and treatment failure) have been presented by frequency/percentages. Duration of hospital stay in days and mean duration of application of respiratory support in hours have been compared using the Mann–Whitney U test according to normality of data. The comparison of adverse effects among both groups was compared using the Chi-square test. A p-value less than or equal to 0.05 was considered significant.

3. Results

3.1. Baseline Characteristics of Study Sample

The comparison of characteristics between Group A and Group B reveals no significant differences in several variables. The mean age (14.72 ± 8.45 days for Group A vs. 15.07 ± 8.02 days for Group B) and gestational age (32.71 ± 2.52 weeks for Group A vs. 32.45 ± 2.94 weeks for Group B) were similar between the two groups, with p-values of 0.796 and 0.472, respectively, indicating no significant differences. The gender distribution showed no notable difference (p = 0.495), with a slightly higher percentage of females in both groups. The Clinical parameters, including APGAR score, SPO2, heart rate (HR), arterial pH, PO2, and PCO2, were similar between the groups (p > 0.05). However, the respiratory rate was higher in Group B (55.75 ± 11.66) compared to Group A (52.29 ± 11.23) (p < 0.05). (Table 1).

3.2. Comparison of Duration of Application of Non-Invasive Ventilatory Support (Hours) and Hospital Stay Between the Groups

The comparison of the duration of application of non-invasive ventilatory support and hospital stay between the two groups shows significant differences. The mean duration of non-invasive ventilatory support was significantly shorter in Group B (HHFNC) at 65.20 h (±15.9) compared to Group A (nCPAP), which had a mean of 72.29 h (±20.7), with a p-value of 0.013, indicating statistical significance. Similarly, the mean duration of hospital stay was significantly shorter in Group B (HHFNC) at 20.14 days (±3.50) compared to Group A (nCPAP), which had a mean of 24.25 days (±6.07), with a p-value of 0.000, confirming a significant difference. These findings suggest support that HHFNC may be associated with a shorter duration of both non-invasive ventilatory support and hospital stay compared to nCPAP (Table 2). The most prevalent adverse impact in the nCPAP group was sepsis, which was documented in eight instances, followed by nasal mucosal damage in seven. Feeding intolerance and stomach distention were reported in five and four patients, respectively. In contrast, the HHFNC group exhibited a greater rate of nasal mucosal damage (18 instances) compared to nCPAP. Feeding intolerance and abdominal distention were recorded in 9 and 6 instances, respectively, whereas sepsis was diagnosed in 10 cases. These findings show that, while both groups suffered similar adverse effects, HHFNC was linked with a greater frequency of nasal mucosal damage, whereas sepsis was more common in the nCPAP group (Figure 1).

3.3. Comparison of Treatment Failure in Both Groups

In the study, the incidence of treatment failure was observed in both the nCPAP and HHFNC groups. Specifically, 10 patients experienced treatment failure in the nCPAP group, while 16 patients faced treatment failure in the HHFNC group. This indicates that a higher proportion of patients in the HHFNC group experienced treatment failure compared to those in the nCPAP group (Figure 2).

3.4. Comparison of Duration of Neonatal Outcome Between the Groups

The neonatal outcomes for both nCPAP and HHFNC groups were compared. Among the total of 220 neonates, 194 (88.2%) were discharged without the need for intubation, with 100 (90.9%) in the nCPAP group and 94 (85.5%) in the HHFNC group. The difference in discharge rates between the two groups was not statistically significant, with a p-value of 0.224. In terms of mortality, 9 neonates (4.1%) expired, with 5 (4.5%) from the nCPAP group and 4 (3.6%) from the HHFNC group. The causes of death included severe respiratory distress, sepsis, and complications related to prematurity. Regarding intubation, 17 neonates (7.7%) required intubation, with a higher incidence in the HHFNC group (12 cases, 10.9%) compared to the nCPAP group (5 cases, 4.5%). However, the p-value suggests that these differences were not statistically significant (Table 3).
The mean survival time was 30.58 days (95% CI: 29.34–31.82) for nCPAP and 22.76 days (95% CI: 21.99–23.53) for HHFNC, indicating longer survival with nCPAP. The median survival time was 33.00 days (95% CI: 30.98–35.02) for nCPAP and 24.00 days (95% CI: 21.91–26.09) for HHFNC. The Kaplan–Meier survival analysis revealed a significant difference in survival between the nCPAP and HHFNC groups (Log-Rank test: χ2 = 32.220, df = 1, p < 0.001) (Figure 3).
The nCPAP significantly reduced the risk of mortality or treatment failure compared to HHFNC (HR = 0.217, p < 0.001), indicating a strong survival advantage. Sepsis independently increased the risk (HR = 0.493, p = 0.030), highlighting its critical impact on neonatal outcomes. Treatment failure was not a significant predictor (HR = 1.128, p = 0.712) (Table 4).

3.5. Comparison of Arterial pH Levels Between HHFNC and nCPAP Groups

The comparison of the arterial pH between the nCPAP and HHFNC was carried out. Among patients receiving nCPAP, 59 (53.6%) had an arterial pH < 7.2, while 51 (46.4%) had a pH > 7.2. In the HHFNC group, 63 (57.3%) had a pH < 7.2, and 47 (42.7%) had a pH > 7.2. The overall distribution of arterial pH between the two groups was not statistically significant (p = 0.58). This suggests no significant difference in arterial pH outcomes between patients managed with nCPAP and those receiving HHFNC (Table 5).

4. Discussion

The nCPAP remains a primary respiratory support modality for neonates experiencing respiratory distress, offering significant benefits despite associated drawbacks such as nasal injury and the need for skilled nursing care [16]. Early initiation of nCPAP has been shown to reduce mechanical ventilation and surfactant administration, particularly in very preterm infants [17]. However, failure rates can reach 15–25%, prompting the exploration of alternative methods like HHFNC, which offers advantages such as reduced nasal trauma and improved ease of use [18]. In recent times, HHFNC has growing acceptance as an alternative respiratory support modality for preterm infants. HHFNC presents certain advantages over nCPAP, such as a reduced incidence of nasal trauma, utilization of patient and parent-friendly nasal prongs, and ease of use [19].
The present study aimed to compare two widely used respiratory support methods, HHFNC and nCPAP, in preterm neonates with respiratory failure. The mean age of preterm neonates was 14.72 ± 8.45 days for Group A and 15.07 ± 8.02 days for Group B. Previous studies reported lower mean ages of 1–2 days respectively, for preterm neonates with type 1 respiratory [20,21]. This considerable variation in mean age could potentially be attributed to differences in the age criteria used to include patients in the respective studies [22].
The gender distribution also showed no notable difference (p = 0.495), with a slightly higher percentage of females in both groups. Other studies reported higher male-to-female ratios of 1.66:1 reported by Sarkar et al. (2018) [23] and Sharma (2018) reported an even higher proportion of male preterm neonates (78.6%) in their study conducted in India [24]. The gestational age was similar between the two groups, indicating no significant differences. It is noteworthy that no previous study has been conducted specifically on preterm neonates in this particular comparison. However, studies conducted on preterm neonates have reported gestational ages of 32.5 ± 1.5 weeks by Shin et al. (2017) in Korea [25].
The mean SPO2 at admission suggests that the patients in this study presented with lower oxygen saturation levels, indicating severely compromised respiration. The higher mean SPO2 observed in the literature suggests better oxygenation levels in their study population, possibly reflecting more favourable respiratory status or different patient characteristics [26]. In contrast, the lower mean SPO2 reported in the prior study implies that their sample population had insufficient oxygenation levels at admission, perhaps indicating more serious respiratory distress [27]. Maintaining proper oxygen levels is critical for controlling hypoxia which can cause organ malfunction and consequences. Differences in mean SPO2 levels between studies might be attributed to patient characteristics, illness severity, or treatment procedures. Consistency in respiratory rate with previous research improves outcomes dependability and generalizability. However, increased respiratory rates may suggest changes in illness severity, patient characteristics, or clinical care strategies [28]. Similarly, the heart rate data from this investigation and the current literature add to the results’ consistency and dependability, as well as their generalizability to comparable patient groups. Previous reports of increased heart rates may imply variations in illness severity, patient characteristics, or clinical care techniques in their research cohorts [29].
Arterial pH levels did not differ significantly between the groups (p = 0.58), indicating similar efficacy in maintaining acid-base balance. This suggests that while nCPAP may improve survival, its impact on pH regulation is comparable to HHFNC. The arterial pH findings reported in this study and reported in other studies highlight consistency in the acid-base status of patients with similar respiratory conditions in different research settings. Acid-base disturbances are crucial indicators of the patient’s overall physiological status and can help identify the underlying cause and guide appropriate management. The similarity in PO2 values suggests comparable oxygenation levels in patients from both cohorts [30].
In this study, the mean duration of non-invasive ventilatory support and duration of hospital stay was significantly shorter in Group B compared to Group A. These results suggest that HHFNC may be associated with a shorter duration of both non-invasive ventilatory support and hospital stay compared to nCPAP. These findings align with results reported previously where the mean duration of application was also higher in the nCPAP group than the HHFNC group (69 ± 94.8 vs. 65 ± 99.9 h), but the difference was not statistically significant [10]. However, it is important to note that other studies have reported different findings. Some studies showed an inverse relation, where the mean duration of application was less in the nCPAP group than in the HHFNC group, but again the difference was not significant [31].
The longer mean duration of application in the nCPAP group in this study suggests that nCPAP may be utilized for a more extended period compared to HHFNC for providing non-invasive ventilatory support in this particular patient population. The variations in the duration of application between different studies may be influenced by differences in patient selection criteria, disease severity, and clinical management approaches. The lack of statistical significance in some studies could be due to the relatively small sample sizes or other factors that contribute to the variability in results.
Our results revealed no statistically significant differences in the rate of discharge without intubation (90.9% for nCPAP vs. 85.5% for HHFNC, p = 0.224) or mortality rates (4.5% vs. 3.6%). However, the intubation rate was higher in the HHFNC group (10.9% vs. 4.5%), though not statistically significant. These results suggest that while both modalities are effective, nCPAP may offer a slight advantage in reducing the need for intubation [32].
The Kaplan–Meier survival analysis demonstrated a significant survival benefit with nCPAP, with a longer mean (30.58 vs. 22.76 days) and median (33 vs. 24 days) survival time (p < 0.001). Cox regression analysis further supported this, showing a significantly lower risk of mortality or treatment failure with nCPAP (HR = 0.217, p < 0.001) [33]. Sepsis independently increased the risk of mortality (HR = 0.493, p = 0.030), highlighting its critical impact on neonatal outcomes. The higher incidence of treatment failure in the HHFNC group (compared to nCPAP) is noteworthy [34]. As reported in the literature indicates that HHFNC may be less effective in cases of severe respiratory distress, necessitating intubation or escalation of care [35,36]. This underscores the importance of patient selection when deciding between HHFNC and nCPAP as initial interventions. Studies advocate for clear clinical criteria to minimize the risk of treatment failure in vulnerable preterm neonates [37].
This study adds to the expanding body of evidence comparing HHFNC and nCPAP for treating respiratory insufficiency in preterm babies. While HHFNC has benefits such as shorter hospital stays and shorter ventilatory support duration, it may also be linked with increased rates of treatment failure and particular side effects such as nasal mucosal damage. These findings highlight the necessity of individualised therapy strategies based on clinical severity and patient-specific characteristics in optimising outcomes. The study’s applicability to other healthcare settings may be restricted, and it may not address long-term effects such as chronic respiratory diseases. Future multicentre research, including bigger, varied populations and standardised techniques, are required.

5. Conclusions

The duration of non-invasive ventilator support, shown by HHFNC, was significantly less when compared to nCPAP. Moreover, the length of hospital stay was also significantly shorter in the HHFNC group than in nCPAP. This suggests that HHFNC might be preferred for providing extended respiratory support in this patient population. Nonetheless, both HHFNC and nCPAP appear safe and effective in supporting preterm neonates through their respiratory challenges. Ultimately, individual patient needs and clinical considerations should guide the selection of the most suitable respiratory support method. Further research is needed to confirm these findings and explore potential strategies for mitigating adverse effects associated with HHFNC.

Author Contributions

Conceptualization, A.H. and A.A.S.; Validation, D.Y.M.; Formal analysis, F.N.; Investigation, D.Y.M.; Data curation, A.A.S.; Writing—original draft, A.H.; Writing—review & editing, F.N., A.A.S. and M.F.S.; Supervision, M.F.S.; Project administration, D.Y.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This quasi-experimental study (Reference No: 247-23) was approved by the Unit of Research Ethics Committee (REC), Registration No: IRB-SPRM/2023-24-I, (2023–2024), University of Lahore Teaching Hospital, Lahore, Pakistan.

Informed Consent Statement

Informed consent was obtained from the parents and the attendees of all participants included in the study. Guardians or parents of the participants were informed of their rights to access, correct, or withdraw their data.

Data Availability Statement

The datasets generated for this study are available in the attachment.

Conflicts of Interest

Author Amber Hassan was employed by Ceinge Biotecnologie Avanzate. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. De Luca, D. Respiratory distress syndrome in preterm neonates in the era of precision medicine: A modern critical care-based approach. Pediatr. Neonatol. 2021, 62, S3–S9. [Google Scholar] [CrossRef]
  2. Ramaswamy, V.V.; More, K.; Roehr, C.C.; Bandiya, P.; Nangia, S. Efficacy of noninvasive respiratory support modes for primary respiratory support in preterm neonates with respiratory distress syndrome: Systematic review and network meta-analysis. Pediatr. Pulmonol. 2020, 55, 2940–2963. [Google Scholar] [CrossRef] [PubMed]
  3. Chen, J.; Lin, Y.; Du, L.; Kang, M.; Chi, X.; Wang, Z.; Chen, Y. The comparison of HHHFNC and NCPAP in extremely low-birth-weight preterm infants after extubation: A single-center randomized controlled trial. Front. Pediatr. 2020, 8, 250. [Google Scholar] [CrossRef] [PubMed]
  4. Malakian, A.; Aramesh, M.R.; Agahin, M.; Dehdashtian, M. Non-invasive duo positive airway pressure ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: A randomized controlled trial. BMC Pediatr. 2021, 21, 1–9. [Google Scholar] [CrossRef] [PubMed]
  5. Kenner, C.; Boykova, M.V. Neonatal Nursing Care Handbook: An Evidence-Based Approach to Conditions and Procedures; Springer Publishing Company: Berlin/Heidelberg, Germany, 2021. [Google Scholar]
  6. Campbell, D.E. Continuing Care of the Infant After Transfer From Neonatal Intensive Care. In Neonatology for Primary Care; American Academy of Pediatrics: Itasca, IL, USA, 2020. [Google Scholar]
  7. Sjöblom, A. Clinical and Physiological Consequences of Preoxygenation Using High-Flow Nasal Oxygen in Emergency Anaesthesia; Karolinska Institutet: Stockholm, Sweden, 2023. [Google Scholar]
  8. Çetinkaya, M.; Atasay, B.; Perk, Y. Turkish Neonatal Society guideline on the transfusion principles in newborns. Turk. Arch. Pediatr. Türk Pediatri Arşivi 2018, 53 (Suppl. S1), S101–S108. [Google Scholar] [CrossRef] [PubMed]
  9. Dunn, M.S.; Kaempf, J.; de Klerk, A.; de Klerk, R.; Reilly, M.; Howard, D.; Ferrelli, K.; O’Conor, J.; Soll, R.F. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics 2011, 128, e1069–e1076. [Google Scholar] [CrossRef] [PubMed]
  10. Murki, S.; Singh, J.; Khant, C.; Dash, S.K.; Oleti, T.P.; Joy, P.; Kabra, N.S. High-flow nasal cannula versus nasal continuous positive airway pressure for primary respiratory support in preterm infants with respiratory distress: A randomized controlled trial. Neonatology 2018, 113, 235–241. [Google Scholar] [CrossRef] [PubMed]
  11. Chang, C.-J.; Chiang, L.-L.; Chen, K.-Y.; Feng, P.-H.; Su, C.-L.; Hsu, H.-S. High-Flow Nasal Cannula versus Noninvasive Positive Pressure Ventilation in Patients with Heart Failure after Extubation: An Observational Cohort Study. Can. Respir. J. 2020, 1, 6736475. [Google Scholar] [CrossRef]
  12. Sreenan, C.; Lemke, R.P.; Hudson-Mason, A.; Osiovich, H. High-flow nasal cannulae in the management of apnea of prematurity: A comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001, 107, 1081–1083. [Google Scholar] [CrossRef]
  13. Lee, C.C.; Mankodi, D.; Shaharyar, S.; Ravindranathan, S.; Danckers, M.; Herscovici, P.; Moor, M.; Ferrer, G. High flow nasal cannula versus conventional oxygen therapy and non-invasive ventilation in adults with acute hypoxemic respiratory failure: A systematic review. Respir. Med. 2016, 121, 100–108. [Google Scholar] [CrossRef] [PubMed]
  14. Dumpa, V.; Avulakunta, I.; Bhandari, V. Respiratory management in the premature neonate. Expert. Rev. Respir. Med. 2023, 17, 155–170. [Google Scholar] [CrossRef] [PubMed]
  15. Yoder, B.A.; Stoddard, R.A.; Li, M.; King, J.; Dirnberger, D.R.; Abbasi, S. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics 2013, 131, e1482–e1490. [Google Scholar] [CrossRef]
  16. Madar, J.; Roehr, C.C.; Ainsworth, S.; Ersdal, H.; Morley, C.; Rüdiger, M.; Skåre, C.; Szczapa, T.; Pas, A.T.; Trevisanuto, D.; et al. European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth. Resuscitation 2021, 161, 291–326. [Google Scholar] [CrossRef]
  17. De Paoli, A.G.; Morley, C.; Davis, P.G. Nasal CPAP for neonates: What do we know in 2003? Arch. Dis. Child.-Fetal Neonatal Ed. 2003, 88, F168–F172. [Google Scholar] [CrossRef] [PubMed]
  18. Manley, B.J. A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants. In 50 Studies Every Neonatologist Should Know; Oxford Academic: New York, NY, USA, 2024; pp. 103–108. [Google Scholar]
  19. Shi, Y.; Muniraman, H.; Biniwale, M.; Ramanathan, R. A review on non-invasive respiratory support for management of respiratory distress in extremely preterm infants. Front. Pediatr. 2020, 8, 270. [Google Scholar] [CrossRef] [PubMed]
  20. Abadesso, C.; Nunes, P.; Silvestre, C.; Matias, E.; Loureiro, H.; Almeida, H. Non-invasive ventilation in acute respiratory failure in children. Pediatr. Rep. 2012, 4, e16. [Google Scholar] [CrossRef] [PubMed]
  21. De Luca, D.; Tingay, D.G.; van Kaam, A.H.; Courtney, S.E.; Kneyber, M.C.J.; Tissieres, P.; Tridente, A.; Rimensberger, P.C.; Pillow, J.J. Epidemiology of neonatal acute respiratory distress syndrome: Prospective, multicenter, international cohort study. Pediatr. Crit. Care Med. 2022, 23, 524–534. [Google Scholar] [CrossRef] [PubMed]
  22. Townsel, C.D.; Emmer, S.F.; Campbell, W.A.; Hussain, N. Gender differences in respiratory morbidity and mortality of preterm neonates. Front. Pediatr. 2017, 5, 6. [Google Scholar] [CrossRef]
  23. Sarkar, M.; Sinha, R.; Roychowdhoury, S.; Mukhopadhyay, S.; Ghosh, P.; Dutta, K.; Ghosh, S. Comparative study between noninvasive continuous positive airway pressure and hot humidified high-flow nasal cannulae as a mode of respiratory support in infants with acute bronchiolitis in pediatric intensive care unit of a tertiary care hospital. Indian J. Crit. Care Med. Peer-Rev. Off. Publ. Indian Soc. Crit. Care Med. 2018, 22, 85. [Google Scholar]
  24. Sharma, D.; Kaur, A.; Farahbakhsh, N.; Agarwal, S. To compare nasal mask with binasal prongs in delivering continuous positive airway pressure for reducing need of invasive ventilation: Randomized controlled trial. J. Matern. Fetal Neonatal Med. 2021, 34, 1890–1896. [Google Scholar] [CrossRef] [PubMed]
  25. Shin, J.; Park, K.; Lee, E.H.; Choi, B.M. Humidified high flow nasal cannula versus nasal continuous positive airway pressure as an initial respiratory support in preterm infants with respiratory distress: A randomized, controlled non-inferiority trial. J. Korean Med. Sci. 2017, 32, 650. [Google Scholar] [CrossRef]
  26. Foglia, E.E.; Carper, B.; Gantz, M.; DeMauro, S.B.; Lakshminrusimha, S.; Walsh, M.; Schmidt, B.; Caplan, M.S.; Laptook, A.R.; Keszler, M.; et al. Association between policy changes for oxygen saturation alarm settings and neonatal morbidity and mortality in infants born very preterm. J. Pediatr. 2019, 209, 17–22. [Google Scholar] [CrossRef]
  27. Sarker, S.K.; Choudhury, U.K.; Mohsin, M.; Mondal, S.K.; Begum, M. Diagnostic validity of ratio between differences of central venous to arterial CO2 and arterial to central venous O2 content in diagnosis of anaerobic metabolism among septic patients. J. Curr. Adv. Med. Res. 2021, 8, 34–38. [Google Scholar] [CrossRef]
  28. Cristea, A.I.; Ren, C.L.; Amin, R.; Eldredge, L.C.; Levin, J.C.; Majmudar, P.P.; May, A.E.; Rose, R.S.; Tracy, M.C.; Watters, K.F.; et al. Outpatient respiratory management of infants, children, and adolescents with post-prematurity respiratory disease: An official American Thoracic Society clinical practice guideline. Am. J. Respir. Crit. Care Med. 2021, 204, e115–e133. [Google Scholar] [CrossRef]
  29. Wu, C.; Chen, X.; Cai, Y.; Xia, J.; Zhou, X.; Xu, S.; Huang, H.; Zhang, L.; Zhou, X.; Du, C.; et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. 2020, 180, 934–943. [Google Scholar] [CrossRef]
  30. Friedman, M.L.; Nitu, M.E. Acute respiratory failure in children. Pediatr. Ann. 2018, 47, e268–e273. [Google Scholar] [CrossRef] [PubMed]
  31. Luo, J.; Duke, T.; Chisti, M.J.; Kepreotes, E.; Kalinowski, V.; Li, J. Efficacy of high-flow nasal cannula vs standard oxygen therapy or nasal continuous positive airway pressure in children with respiratory distress: A meta-analysis. J. Pediatr. 2019, 215, 199–208. [Google Scholar] [CrossRef]
  32. Huang, H.-W.; Sun, X.-M.; Shi, Z.-H.; Chen, G.-Q.; Chen, L.; Friedrich, J.O.; Zhou, J.-X. Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: A systematic review and meta-analysis of randomized controlled trials. J. Intensive Care Med. 2018, 33, 609–623. [Google Scholar] [CrossRef]
  33. Ann Skariah, T.; Dias, L.; Edward Lewis, L. Comparison of the Heated Humidified High-flow Nasal Cannula with Nasal Continuous Positive Airway Pressure as Primary Respiratory Support for Preterm Neonates: A Prospective Observational Study. Iran. J. Neonatol. 2019, 10, 51–57. [Google Scholar]
  34. Shaaban, H.A.; Aly, H.H.; Ramadan, M.A.; Gad, T.M. The Effect of Ventilatory Supports on Oxidative Stress Biomarkers in Preterm Respiratory Distress. Ain Shams Med. J. 2024, 75, 988–998. [Google Scholar] [CrossRef]
  35. Asseri, A.A.; AlQahtani, Y.A.; Alhanshani, A.A.; Ali, G.H.; Alhelali, I. Indications and safety of high flow nasal cannula in pediatric intensive care unit: Retrospective single center experience in Saudi Arabia. Pediatr. Health Med. Ther. 2021, 12, 431–437. [Google Scholar] [CrossRef]
  36. Awad, A.H.; El-Farrash, A.R.; Shinkar, D.M.; Aly, Y.A.F.; Soliman, N.; Alhassanin, A.H. A study of heated, humidified high flow nasal cannula as an initial respiratory support in preterm neonates. QJM An. Int. J. Med. 2021, 114 (Suppl. S1), hcab113.010. [Google Scholar] [CrossRef]
  37. Jose, D.; Parameswaran, N. Advances in management of respiratory failure in children. Indian J. Pediatr. 2023, 90, 470–480. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Comparison of adverse effects in both groups.
Figure 1. Comparison of adverse effects in both groups.
Biomedicines 13 00602 g001
Figure 2. Comparison of treatment failure in both groups.
Figure 2. Comparison of treatment failure in both groups.
Biomedicines 13 00602 g002
Figure 3. Kaplan–Meier survival analysis between the nCPAP and HHFNC groups.
Figure 3. Kaplan–Meier survival analysis between the nCPAP and HHFNC groups.
Biomedicines 13 00602 g003
Table 1. Comparison between the Groups at Baseline.
Table 1. Comparison between the Groups at Baseline.
CharacteristicsGroup A (n = 128)Group B (n = 128)p-Value
Age (1–28 days)14.72 ± 8.4515.07 ± 8.020.796 a
Gender
Male44 (40.0%)49 (44.5%)0.495 b
Female66 (60.0%)61 (55.5%)
Gestational Age (week) 32.71 ± 2.5232.45 ± 2.940.472 a
APGAR Score at 5 min5.98 + 0.885.46 + 0.810.971 a
SPO2 (%)69.69 ± 18.270.43 ± 17.380.735 a
Respiratory Rate (bpm)52.29 ± 11.2355.75 ± 11.660.028 a
HR Rate (bpm)134.28 ± 18.69133.46 ± 17/830.765 a
Arterial pH7.26 ± 1.377.09 ± 1.410.301 a
PCO2 (mmHg)63.31 ± 12.163.02 ± 11.50.941 a
PO2 (mmHg)40.56 ± 5.4239.87 ± 5.230.344 a
a Mann-Whitney U test. b Chi-Square test. Taking p-value ≤ 0.05 as significant.
Table 2. Comparison of Duration of Application of Non-invasive Ventilatory Support (hours) and hospital stay between the Groups.
Table 2. Comparison of Duration of Application of Non-invasive Ventilatory Support (hours) and hospital stay between the Groups.
Duration of Application of Non-Invasive Ventilatory Support (Hours)
Study GroupMeanStd. Deviationp-Value
nCPAP (A)72.2920.70.013 a
HHFNC (B)65.2015.9
Hospital stays in days
nCPAP (A)24.256.070.000 a
HHFNC (B)20.143.50
a Mann-Whitney test, Taking p-value ≤ 0.05 as significant.
Table 3. Comparison of Duration of Neonatal Outcome between the Groups.
Table 3. Comparison of Duration of Neonatal Outcome between the Groups.
Neonatal OutcomeGroupsTotalp-Value
nCPAPHHFNC
Discharged without the need for intubation100 (90.9%)94 (85.5%)194 (88.2%)a 0.224
Expired5 (4.5%)4 (3.6%)9 (4.1%)
Intubated5 (4.5%)12 (10.9%)17 (7.7%)
Total110110220
a Chi-Square test. Taking p-value ≤ 0.05 as significant.
Table 4. Cox Regression Analysis for Survival Outcomes.
Table 4. Cox Regression Analysis for Survival Outcomes.
VariableBSEWaldp-ValueHazard Ratio (Exp B)95% CI for Exp (B)
Treatment Group (nCPAP vs. HHFNC)−1.5260.29526.8060.0000.217(0.123–0.382)
Sepsis−0.7070.3264.6970.030.493(0.257–0.947)
Treatment Failure0.1200.3260.1360.711.128(0.588–2.163)
Table 5. Comparison of Arterial pH between the Groups.
Table 5. Comparison of Arterial pH between the Groups.
Arterial pHGroupsTotalp-Value
nCPAPHHFNC
<7.259 (53.6%)63 (57.3%)122 (55.5%)a 0.58
>7.251 (46.4%)47 (42.7%)98 (44.5%)
Total110110220
a Chi-Square test. Taking p-value ≤ 0.05 as significant.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Yousof Mahboob, D.; Hassan, A.; Naheed, F.; Ali Shah, A.; Fareed Siddiqui, M. Effectiveness of Humidified High Flow Nasal Cannula Versus Continuous Nasal Positive Airway Pressure in Managing Respiratory Failure in Preterm Infants: An Emergency Department Study. Biomedicines 2025, 13, 602. https://doi.org/10.3390/biomedicines13030602

AMA Style

Yousof Mahboob D, Hassan A, Naheed F, Ali Shah A, Fareed Siddiqui M. Effectiveness of Humidified High Flow Nasal Cannula Versus Continuous Nasal Positive Airway Pressure in Managing Respiratory Failure in Preterm Infants: An Emergency Department Study. Biomedicines. 2025; 13(3):602. https://doi.org/10.3390/biomedicines13030602

Chicago/Turabian Style

Yousof Mahboob, Duaa, Amber Hassan, Faiza Naheed, Arshad Ali Shah, and Maria Fareed Siddiqui. 2025. "Effectiveness of Humidified High Flow Nasal Cannula Versus Continuous Nasal Positive Airway Pressure in Managing Respiratory Failure in Preterm Infants: An Emergency Department Study" Biomedicines 13, no. 3: 602. https://doi.org/10.3390/biomedicines13030602

APA Style

Yousof Mahboob, D., Hassan, A., Naheed, F., Ali Shah, A., & Fareed Siddiqui, M. (2025). Effectiveness of Humidified High Flow Nasal Cannula Versus Continuous Nasal Positive Airway Pressure in Managing Respiratory Failure in Preterm Infants: An Emergency Department Study. Biomedicines, 13(3), 602. https://doi.org/10.3390/biomedicines13030602

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop