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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 168-174

Heated humidified high-flow nasal cannula versus nasal continuous positive airways pressure for respiratory support in preterm neonates – A noninferiority trial at a tertiary care center


1 Department of Neonatology, Dr. Bidari's Ashwini Hospital, Vijayapura, Karnataka, India
2 Department of Pediatrics, Dr. Bidari's Ashwini Hospital, Vijayapura, Karnataka, India

Date of Submission13-Feb-2020
Date of Decision12-Apr-2020
Date of Acceptance13-Apr-2020
Date of Web Publication07-Aug-2020

Correspondence Address:
Dr. Siddu Charki
Chief Consultant Neonatologist, Dr. Bidari's Ashwini Hospital and Post-Graduation Center, Vijayapur, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_76_19

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  Abstract 


Background: In the neonatal period, respiratory failure remains a difficult challenge and is associated with high morbidity and mortality. Humidified high-flow nasal cannula (HHFNC) is being used as an alternative form of respiratory support for preterm infants with respiratory distress syndrome, apnea, and chronic lung disease. Objective: The objective was to assess the indications, frequency of usage, efficacy, and safety of heated HHFNC (HHHFNC) as compared to nasal continuous positive airway pressure (NCPAP) in providing respiratory support in preterm neonates after a period of positive pressure ventilation. (postextubation). Materials and Methods: This study was conducted in a Level II b neonatal intensive tertiary care unit in North Karnataka, India. In this study, all preterm neonates less than 37 weeks of gestation were placed on one of the respiratory supports (HHHFNC or NCPAP), immediately following extubation from mechanical ventilation. The primary outcome measures assessed were death, days on mechanical ventilation, need for reintubation (failure), air leak, nasal injury, and bronchopulmonary dysplasia (BPD). Results: There were no significant differences in major clinical outcomes including death, BPD, ventilator-days, necrotizing enterocolitis, severe intraventricular hemorrhage, retinopathy of prematurity, or time to full feeds. Failure of assigned mode of respiratory support was seen in 12% of infants on HHHFNC compared to 16% on NCPAP (P = 0.48). No significant difference in other outcome measures was seen between the groups. No nasal injury was observed in the HHHFNC group against 10% in the NCPAP group (P = 0.55). Conclusion: There was no statistically significant difference within the primary and secondary outcomes. At 5% level of significance, HHHFNC was found to be noninferior compared to NCPAP with 3.5% difference in the rates of failure of assigned mode of respiratory support. Hence, HHHFNC can be considered to be a safe, efficacious, and more easily acceptable mode of respiratory support as compared to NCPAP in preterm neonates after a period of positive pressure ventilation.

Keywords: High-flow nasal cannula, nasal continuous positive airways pressure, neonate, post extubation, respiratory distress or disease


How to cite this article:
Charki S, Patil PK, Hadalgi L, Kulkarni T, Loni R, Karva M M, Bidari LH. Heated humidified high-flow nasal cannula versus nasal continuous positive airways pressure for respiratory support in preterm neonates – A noninferiority trial at a tertiary care center. J Clin Neonatol 2020;9:168-74

How to cite this URL:
Charki S, Patil PK, Hadalgi L, Kulkarni T, Loni R, Karva M M, Bidari LH. Heated humidified high-flow nasal cannula versus nasal continuous positive airways pressure for respiratory support in preterm neonates – A noninferiority trial at a tertiary care center. J Clin Neonatol [serial online] 2020 [cited 2020 Sep 25];9:168-74. Available from: http://www.jcnonweb.com/text.asp?2020/9/3/168/291651




  Introduction Top


In the neonatal period, respiratory failure is a difficult challenge and is associated with high morbidity and mortality. In neonates, respiratory support can be provided either through invasive or noninvasive ventilation. Noninvasive ventilation includes supplemental oxygen via a head box or by nasal cannula; continuous positive airway pressure (CPAP) via nasal prongs or mask; and heated humidified high-flow nasal cannula (HHHFNC).[1],[2]

Nasal CPAP (NCPAP) improves the residual lung capacity, prevents atelectasis of alveoli, and recruits them, thereby reducing apnea. NCPAP applied postextubation reduces the rates of extubation failure.[3],[4],[5]

In contrast, “high-flow” nasal cannula (HFNC) delivers oxygen or blended oxygen and air at higher flow rates (>2 L/min). Gas given via HFNC is routinely heated and humidified, as with CPAP. High gas flows that is between 2 and 8 l/min in preterm neonates may provide low levels of positive end-expiratory pressure (PEEP).[6],[7]

NCPAP is a recognized mode of respiratory support for preterm neonates. Recently, the practice of HHHFNC usage has become an increasingly popular alternative to NCPAP for noninvasive support of preterm neonates after extubation.

The increasing use of HHHFNC is, in part, due to its greater comfort of use, better patient compliance, and similar effectiveness to NCPAP. In addition, there are decreased incidences of nasal trauma and nares distortion compared to NCPAP.[8]

Hence, this study was performed to assess whether HHHFNC is as effective and safe as NCPAP in providing respiratory support in preterm neonates (postextubation).

Aims and objectives

  1. The aims and objectives were to assess the efficacy of HHHFNC as compared to NCPAP in providing respiratory support in preterm neonate's post extubation
  2. To assess the safety of HHHFNC as compared to NCPAP in providing respiratory support in preterm neonate's post extubation.



  Materials and Methods Top


This study was conducted in a Level II b neonatal intensive tertiary care unit in North Karnataka. In this study, all preterm neonates less than 37 weeks of gestation were placed on one of the respiratory supports (HHHFNC or NCPAP), immediately following extubation from mechanical ventilation based on clinicians' discretion and unit protocol.

Inclusion criteria

Preterm neonates <37 weeks of gestation who required ventilation during the first 96 h of life and postextubation being placed on either HHHFNC or NCPAP were included in the study.

Exclusion criteria

  • Antenatally detected life-threatening congenital heart diseases
  • Babies who were subsequently discharged against medical advice.


Treatment failure was defined by

  • A FiO2 of 20% or more above the baseline value prior to extubation to achieve a peripheral oxygen saturation of more than 90%
  • FiO2 >60% to achieve a PO2 >50 mmHg on an arterial blood gas
  • A pH <7.2 on an arterial blood gas with pCO2 >60 mmHg
  • More than one apnoeic episode requiring positive pressure ventilation within 24 h postextubation and,
  • Need for reintubation and ventilation within 72 h of extubation as determined by the treating clinician.


Neonates in the HHHFNC group received flows via the Fischer and Paykel junior kit (RT330, Maurice Paykel Place, East Tamaki Auckland, New Zealand.).

Neonates were fitted with nasal prongs that occluded more than 50% of the nares. The starting flow rates were based on the weight (2 L/kg). The staring FiO2 was usually 21%–40% and then adjusted to maintain target oxygen saturation.

Neonates in the NCPAP group received PEEP via the binasal midline prongs (Fischer and Paykel Healthcare). NCPAP was generated with the use of an underwater bubble system. The starting PEEP was 4–6 cmH2O, flow rates of 5–8 L/min, and FiO2 of 21%–40%.

Outcomes

Primary outcomes

  • Failure of assigned mode of respiratory support (treatment failure criteria mentioned above)
  • Chronic lung disease
  • Death of the neonate prior to discharge.


Secondary outcomes

  • Retinopathy of prematurity (ROP)
  • Intraventricular hemorrhage (IVH)
  • Nosocomial sepsis (blood culture or cerebrospinal fluid positive. Sample taken post extubation)
  • Severe necrotizing enterocolitis (NEC) (Stage II or more according to Bells criteria)
  • Nasal trauma (erythema or erosion of the nasal septum or nasal mucosa)
  • Air leak syndromes (pneumothorax, pneumomediastinum and pulmonary interstitial emphysema)
  • Patent ductus arteriosus (PDA)
  • Duration of respiratory support (days/hours)
  • Duration of supplementary oxygen
  • Duration of hospitalization (days)
  • Number of days to attain full feeds that is 120 ml/kg/day
  • Weight gain prior to discharge (grams).


Data were represented using mean ± standard deviation and analyzed by Chi-square test for association, with comparison of means using t-test, ANOVA, and diagrammatic presentation.


  Results Top


The study was performed in a Level II B neonatal intensive care unit (NICU) in a tertiary care hospital in North Karnataka. A total of 106 neonates less than 37 weeks of gestation were enrolled in the study. All of these neonates had required invasive ventilation within the first 96 hours of life. Among 106 neonates, post extubation, 54 babies were put on NCPAP, whereas 52 were put on HHHFNC mode of respiratory support. There were no differences noted in the baseline characteristics between the comparison groups such as mean gestation, birth weight, and gender distribution [Table 1] and [Figure 1].
Table 1: Distribution of Baseline Characteristics of Study Groups.

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Figure 1: Distribution of baseline parameters

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Primary outcomes

Failure of assigned mode of respiratory support

Failure of the assigned modality of respiratory support post extubation (as defined by the criteria mentioned above) was seen in five babies in the HHHFNC group and three babies in the NCPAP group. This difference was not statistically significant [Table 2] and [Figure 2].
Table 2: Failure of Assigned Means of Respiratory Support Between Study Groups

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Figure 2: Failure of assigned means of respiratory support between the study groups

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Chronic lung disease

Chronic lung disease was seen in three babies in the HHHFNC group and two babies in the NCPAP group. This difference was not statistically significant [Table 3] and [Figure 3].
Table 3: Distribution of Chronic Lung Disease Between Study Groups

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Figure 3: Distribution of chronic lung disease between the study groups

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Death of the baby prior to discharge

Death of the baby prior to discharge was seen in three babies put on HHHFNC post extubation and two babies on NCPAP. This difference was statistically not significant [Table 4] and [Figure 4].
Table 4: Death Prior To Discharge Between Study Groups

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Figure 4: Death prior to discharge between the study groups

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Secondary outcomes

There were no significant differences in secondary outcomes including ROP, IVH, nosocomial infection, PDA, air leaks, days on respiratory support, days on supplemental oxygen, duration of hospital stay, and weight gain (kg). Outcomes such as NEC, nasal trauma, and days to reach full feeds show statistically significant difference between the HHHFNC and NCPAP groups [Table 5].
Table 5: Secondary Outcomes of The Study Groups.

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  Discussion Top


The use of HHHFNC has increased significantly in recent years in NICUs all over the world. This is mainly because of the ease of application and better patient tolerance. Also, it has got added advantages such as minimal nasal trauma and less interference with feeding or kangaroo mother care as compared to NCPAP. Despite its wide acceptance clinically, there is sparse data regarding its efficacy and safety in preterm neonates' post extubation. Clinical outcomes associated with the use of HHHFNC are being considered to be at least similar to those of NCPAP usage by some neonatologists. On the basis of our prespecified definition of noninferiority, the use of HHHFNC was found to be noninferior to NCPAP as a means of respiratory support in preterm neonates after a period of positive pressure ventilation.

Earlier randomized controlled trials (RCTs) (comparing NCPAP and HHHFNC or different high-flow devices) between 2006 and 2010 had relatively small study samples and low flow rates compared to the current practice.[3],[9],[10]

In 2013, the publication of three large RCTs added to the evidence for the use of HHHFNC.

The first by Collins et al.[11] included 132 neonates <32 weeks of gestation, who were randomized to either HHHFNC or NCPAP after extubation. The rates of extubation failure did not differ significantly (22% in the HHHFNC group and 34% in the NCPAP group). Also, the rates of reintubation were not statistically significant (17% in the HHHFNC group and 24% in the NCPAP group).

A similar study by Manley et al.[8] compared HHHFNC and NCPAP using a noninferiority design. Three hundred and three preterm neonates were included in the study. Treatment failure as defined by prespecified criteria occurred in 34.2% of neonates in the HHHFNC group and 25.8% of neonates in the NCPAP group. Reintubation was required within 7 days of extubation in 17.8% of neonates in the HHHFNC group compared to 25.2% in the NCPAP group.

The third RCT by Yoder et al.[12] included neonates between 28 and 42 weeks of gestational age. A total of 291 babies were randomized to HHHFNC or NCPAP after extubation, and the primary outcome of need for reintubation within 72 h (11.6% in HHHFNC and 6.5% in NCPAP group) did not differ significantly between the two groups.

A Cochrane review updated in 2016[13] observed six studies, including 934 neonates who were randomized to either HHHFNC or NCPAP as postextubation means of respiratory support. A meta-analysis demonstrated no additional risk of treatment failure in the HHHFNC group. It also suggested that in neonates from 28 to 32 weeks of gestation, HHHFNC (with the availability of rescue CPAP) may be an appropriate modality of respiratory support after extubation.

Our study was done at a tertiary care center in the district of Vijayapura in Karnataka. A total of 106 neonates below 37 weeks of gestation were included in the study. After a period of positive pressure ventilation, they were placed on either HHHFNC or NCPAP. Fifty-four babies were placed on HHHFNC, while 52 babies received NCPAP. The primary characteristics were similar in both the study groups. The primary outcomes of the study were failure of assigned mode of respiratory support, chronic lung disease, and death during respiratory support.

Failure of the assigned means of respiratory support was seen in five babies in the HHHFNC group and three babies in the NCPAP group. This difference was statistically not significant. Similar results were obtained in the study by Yoder et al. and Manley et al.

Chronic lung disease was defined as requirement of supplemental oxygen at 36 weeks of post gestational age for neonates born at <32 weeks of gestation or 28 days of age for neonates born at 32 weeks of gestation or later.

In our study, 5.6% of neonates on HHHFNC developed chronic lung disease (CLD), whereas 3.7% of neonates on NCPAP developed CLD. This difference was not statistically significant. The findings were similar to the study conducted by Manley et al. and Yoder et al., in which the difference in the incidence of chronic lung disease in both the study groups was not statistically significant.

Death of the neonate prior to discharge was seen in three babies from the HHHFNC group and two babies in the NCPAP group. This difference was statistically not significant. This finding was similar to that observed in the study conducted by Manley et al. [Table 6].
Table 6: Comparison of the Outcomes with Other Studies.

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Secondary outcomes of the study were ROP, NEC, IVH, nasal trauma, nosocomial infection, air leaks, and opening up of PDA.

Most of the parameters showed no statistically significant difference between the HHHFNC and NCPAP groups except nasal trauma and incidence of NEC which were more in the NCPAP group.

The incidence of ROP, IVH, air leaks, nosocomial infection, and PDA was comparable between the two groups in our study. These findings were similar to the observations by Manley et al.

The incidence of NEC was more in the NCPAP group as compared to the HHHFNC group in our study, and this difference was statistically significant.

The incidence of nasal trauma was more in the NCPAP group as compared to the HHHFNC group, and this difference was statistically significant in our study. These findings were similar to the observations by Manley et al.

The number of days on respiratory support, number of days on oxygen, and duration of hospital stay were comparable between the NCPAP and HHHFNC groups. These findings were similar to those in the study by Manley et al. However, in our study, the duration required to reach full feeds was longer in the NCPAP group as compared to the HHHFNC group, with the difference being statistically significant. This finding did not correlate with that of Manley's study.

At 5% level of significance, HHHFNC was found to be noninferior compared to NCPAP with 3.5% difference in the rates of failure of assigned mode of respiratory support. In fact, it had added advantages such as minimal nasal trauma, less incidence of NEC, and lesser number of days required to reach full feeds.

Although this study is limited by small sample size, the lack of randomization of the samples into the HHHFNC group or NCPAP group, data presented here indicate that HHFNC is better tolerated and an effective alternative respiratory support mode to NCPAP in the preterm infant population.


  Conclusion Top


There was no statistically significant difference in the primary and secondary outcomes. It was observed that babies on HHHFNC had lesser incidence of nasal trauma, NEC, and lesser number of days required to reach full feeds. Hence, it can be said that HHHFNC was not inferior compared to NCPAP as a postextubation mode of respiratory support. At 5% level of significance, HHHFNC was found to be noninferior compared to NCPAP with 3.5% difference in the rates of failure of assigned mode of respiratory support. Hence, HHHFNC can be considered to be a safe, efficacious, and more easily acceptable mode of respiratory support as compared to NCPAP in preterm neonates after a period of positive pressure ventilation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wilkinson D, Andersen C, O'Donnell CP, De Paoli AG. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev 2011;5:CD006405.  Back to cited text no. 1
    
2.
Davis PG, Henderson-Smart DJ. Nasal continuous positive airway pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev 2003; CD000143.  Back to cited text no. 2
    
3.
Campbell DM, Shah PS, Shah V, Kelly EN. Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants. J Perinatol 2006;26:546-9.  Back to cited text no. 3
    
4.
De Paoli AG, Morley C, Davis PG. Nasal CPAP for neonates: What do we know in 2003? Arch Dis Child Fetal Neonatal Ed 2003;88:F168-72.  Back to cited text no. 4
    
5.
Morley C, Davis P. Continuous positive airway pressure: Current controversies. Curr Opin Pediatr 2004;16:141-5.  Back to cited text no. 5
    
6.
Wilkinson DJ, Andersen CC, Smith K, Holberton J. Pharyngeal pressure with high-flow nasal cannulae in premature infants. J Perinatol 2008;28:42-7.  Back to cited text no. 6
    
7.
Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: Mechanisms of action. Respir Med 2009;103:1400-5.  Back to cited text no. 7
    
8.
Manley BJ, Owen LS, Doyle LW, Anderson CC, Cartwright DW, Pritchard MA, et al. High flow nasal cannula in very preterm infants after extubation. N Engl J Med 2013;369:1425-33.  Back to cited text no. 8
    
9.
Miller SM, Dowd SA. High-flow nasal cannula and extubation success in the premature infant: A comparison of two modalities. J Perinatol 2010;30:805-8.  Back to cited text no. 9
    
10.
Woodhead DD, Lambert DK, Clark JM, Christensen RD. Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: A prospective, randomized, masked, crossover trial. J Perinatol 2006;26:481-5.  Back to cited text no. 10
    
11.
Collins CL, Holberton JR, Barfield C, Davis PG. A randomized control trial to compare heated humidified high flow nasal cannulae with nasal continuous positive airway pressure post extubation in premature infants. J Pediatr 2013;162:949-54E1.  Back to cited text no. 11
    
12.
Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics 2013;131:e1482-90.  Back to cited text no. 12
    
13.
Wilkinson D, Andersen C, O'Donnell CPF, De Paoli AG, Manley BJ. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev 2016;2:CD006405.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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