Original Paper

Neonatology 2018;113:235–241 Received: August 21, 2017

Accepted after revision: October 18, 2017
DOI: 10.1159/000484400 Published online: January 23, 2018

High-Flow Nasal Cannula versus Nasal Continuous

Positive Airway Pressure for Primary Respiratory
Support in Preterm Infants with Respiratory
Distress: A Randomized Controlled Trial
Srinivas Murki a Jayesh Singh a Chiragkumar Khant b Swarup Kumar Dash b
       

Tejo Pratap Oleti a Percy Joy a Nandkishor S. Kabra b

     

a Fernandez Hospital, Hyderabad, India; b Surya Hospital, Mumbai, India

 

Keywords received mechanical ventilation. Results: During the study

High-flow nasal cannula · Nasal continuous positive airway period, 139 and 133 infants were randomized to the nCPAP
pressure · Respiratory distress · Preterm infant and HFNC groups, respectively. The study was stopped after
an interim analysis showed a significant difference (p <
0.001) in the primary outcome between the 2 groups. The
Abstract treatment failure was significantly higher in the HFNC group
Background: Nasal continuous positive airway pressure (HFNC, n = 35, 26.3%, vs. CPAP, n = 11, 7.9%, risk difference
(nCPAP) is the standard noninvasive respiratory support for 18.4 percentage points, 95% CI 9.7–27). Among the infants
newborns with respiratory distress. Evidence for high-flow in the HFNC group who had treatment failure (n = 35), 32
nasal cannula (HFNC) as an alternative mode of respiratory were initially rescued with CPAP. The rate of mechanical
support is inconclusive. Objective: The aim of this work was ventilation in the first 3 and 7 days of life was similar be-
to evaluate whether HFNC is not inferior to nCPAP in reduc- tween the 2 groups. Treatment failure was significantly
ing the need for higher respiratory support in the first 72 h higher in the HFNC group per protocol and also in the sub-
of life when applied as a noninvasive respiratory support groups of infants with moderate (Silverman Anderson score,
mode for preterm neonates with respiratory distress. Meth- SAS ≤5) or severe respiratory distress (SAS score >5). Con-
ods: Preterm infants (gestation ≥28 weeks and birth weight clusions: When comparing HFNC to nCPAP as a primary
≥1,000 g) with respiratory distress were randomized to ei- noninvasive respiratory support in preterm infants with
ther HFNC or nCPAP in a non-inferiority trial. Failure of the respiratory distress, HFNC is inferior to nCPAP in avoiding
support mode in the first 72 h after birth was the primary the need for a higher mode of respiratory support in the first
outcome. Infants failing HFNC were rescued either with 72 h of life. © 2018 S. Karger AG, Basel
nCPAP or mechanical ventilation, and those failing nCPAP
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© 2018 S. Karger AG, Basel Srinivas Murki

Universidad Peruana Cayetano

Chief Neonatologist
Fernandez Hospital
E-Mail [email protected]
Hyderguda, Hyderabad 500029 (India)
www.karger.com/neo
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E-Mail srinivasmurki2001 @ gmail.com

 Introduction randomized to HFNC (Optiflow Junior or AIRVO 2, Fisher and
Paykel Healthcare, Auckland, New Zealand), the nasal prong’s
outer diameter was to occupy <50% of the nares internal diameter.
Nasal continuous positive airway pressure (nCPAP) is Free egress of flow around the cannula was auscultated by the bed-
the standard respiratory support for most newborns with side nurse. The initial flow rate was 5 L/min (LPM). FiO2 was ad-
respiratory distress. Irrespective of the cause, most new- justed to maintain SpO2 between 90 and 95%. The flow rate was
borns would benefit from this effective therapy. Started increased by 1 LPM up to a maximum of 7 LPM when: (a) FiO2
early in the delivery room or within the first hour of re- increased by 0.10 above the starting FiO2, (b) pCO2 increased by
10 mm Hg above the baseline, (c) Silverman Anderson score (SAS)
spiratory distress, nCPAP would reduce the need for me- [11] increased by 1 from the baseline, or (d) lung expansion was
chanical ventilation and surfactant administration in very decreased on the chest radiograph (<6 posterior intercostal spac-
preterm infants. nCPAP, however, is associated with na- es). The flow rate was reduced in steps of 0.5–1.0 LPM when all of
sal injury, frequent prong displacement, increased nurs- the following were sustained for a 6-h period: (a) FiO2 <0.30 and
ing time, and a need for skilled nursing staff [1]. nCPAP oxygen saturation between 90 and 95%, (b) pCO2 between 40 and
60 mm Hg, and (c) no signs of respiratory distress (SAS <3). HFNC
failures do occur in nearly 15–25% of the newborns sup- was removed and the infant was started on room air when FiO2
ported on it [2, 3]. High-flow nasal cannula (HFNC), an was 0.21 and SAS was ≤3.
alternative mode of respiratory support, is increasingly Infants randomized to the nCPAP group were started on a
being accepted for the care of preterm infants [4–6]. A CPAP generator (Fisher and Paykel Healthcare) using short bina-
lower incidence of nasal trauma, patient and parent sal prongs (Hudson Respiratory Care Inc., Temecula, CA, USA, or
Fisher and Paykel Healthcare) or nasal masks (Fisher and Paykel
friendly nasal prongs, and ease of use are the advantages Healthcare). The initial CPAP pressure was 5 cm of H2O, and FiO2
of this device over nCPAP [7, 8]. HFNC is not inferior to was adjusted to maintain SpO2 between 90 and 95%. CPAP pres-
nCPAP in newborns extubated from mechanical ventila- sures were adjusted on the same criteria as used for flow rate in the
tion [9, 10]. There is a need for more evidence on the role HFNC group. nCPAP was removed and the infant was started on
of HFNC in the primary management of newborns with standard nasal prong oxygen when the FiO2 requirement was
<0.30 and CPAP pressure was ≤4 cm for at least 6 h.
respiratory distress and hence we planned this study to Surfactant was used for infants with respiratory distress syn-
evaluate if “HFNC is not inferior to nCPAP in reducing drome (RDS) on the chest X-ray and FiO2 was >0.30. Surfactant
the need for higher respiratory support in the first 72 h of was administered by the InSurE technique, and the infant was ex-
life when applied as a noninvasive respiratory support tubated to the existing support mode after extubation. A second
mode for preterm neonates with respiratory distress.” dose of surfactant was administered if FiO2 remained above 0.30
for 6 h after the first dose.

Outcomes
Methods Failure of the support mode was the primary outcome. Treat-
ment failure was defined as the infant receiving maximum support
The study was approved by our institutional ethics committees (flow rate of >7 LPM in the HFNC group or CPAP pressure >7 cm
and was registered prospectively in the clinical trial registry of In- of H2O in the nCPAP group) and having 1 of the following: (a)
dia (CTRI/2015/08/006108). FiO2 >0.60, (b) pH <7.20 and PaCO2 > 60 mm Hg, (c) an increase
in SAS >2, (d) recurrent apnea (>4 episodes/h) or apnea requiring
Study Design bag and mask ventilation, or (e) shock with severe metabolic aci-
This was an open-label, multicenter, 2-arm parallel, stratified dosis (base excess >–10). Infants with treatment failure received
randomized controlled trial. nCPAP or mechanical ventilation in the HFNC group and me-
chanical ventilation in the nCPAP group.
Participants and Settings The secondary outcomes included the need for mechanical ven-
The study was conducted at the NICUs of 2 tertiary care hos- tilation in the first 72 h and in the first 7 days of life, the need for
pitals from 9th October 2015 to 26th November 2016. Preterm higher respiratory support or intubation for surfactant, the dura-
infants with a gestation ≥28 weeks and birth weight ≥1,000 g and tion of noninvasive ventilation (either nCPAP or HFNC), the dura-
respiratory distress within the first 6 h of birth were eligible for tion of ventilation, and the duration of oxygen therapy. The other
inclusion in the study. Respiratory distress was defined as the pres- outcomes included nasal injury at discharge (dilation of nares, col-
ence of tachypnea, chest retraction and grunting (either of the umella damage or altered shape of the nose, skin excoriation), neo-
two). Infants with major malformations and those intubated in the natal mortality, pulmonary air leaks, hemodynamically significant
delivery room were excluded. patent ductus arteriosus, necrotizing enterocolitis (modified Bell’s
stage) [12], culture-positive sepsis, supplemental oxygen at 28 days
Interventions of life, bronchopulmonary dysplasia (supplemental oxygen at 36
Parents were approached for consent before the birth of their weeks postmenstrual age), intraventricular hemorrhage (grade III
baby or at admission to the NICU. Infants were randomized on or IV) [13], cystic periventricular leukomalacia [14], and retinopa-
admission to the NICU. The infants were cared for on a “T piece” thy of prematurity (requiring laser or surgery). Data were collected
with CPAP pressure set at 5 cm until randomization. For infants until death or discharge from the hospital.
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 Color version available online
Assessed for eligibility:
weight ≥1,000 g and gestation ≥28 weeks (n = 1,716)

Excluded (n = 1,444)
• not meeting inclusion criteria (n = 1,146)
• intubation at birth (n = 89)
Enrolment • major malformation (n = 24)
• study device not available (n = 52)
• refused consent (n = 64)
• missed randomization (n = 69)

Randomized (n = 272)

Allocation

Allocated to intervention“HFNC” (n = 133) Allocated to intervention“nCPAP” (n = 139)

• received allocated intervention (n = 133) • received allocated intervention (n = 139)
• did not receive allocated intervention (n = 0) • did not receive allocated intervention (n = 0)

Follow-up

Lost to follow-up (n = 0) Lost to follow-up on day 4 of life (n = 1)

Discontinued intervention (n = 0) Discontinued intervention (n = 0)

Analysis

Analyzed (n = 133) Analyzed (n = 139)

Excluded from analysis (n = 0) Primary outcome (n = 139)
Excluded from analysis for secondary
outcomes (n = 1, transferred to other
hospital on day 4 of life)

Fig. 1. Flow diagram of the study participants.

Sample Size Statistical Methods

Assuming a 20% failure rate in the nCPAP group, with a non- Categorical variables were compared with the Fisher exact test,
inferiority trial design (80% power and 1-sided alpha 5%) with an while continuous variables were analyzed using the 2-sample t test
expected failure of 25% in the HFNC group and a non-inferiority or the Mann-Whitney U test as appropriate. Significance was de-
margin of 5%, the required sample size was 218 patients in each fined as p < 0.05. All the outcomes were analyzed on an intention
group (http://powerandsamplesize.com). We chose 5% non-infe- to treat analysis and also on a per protocol basis. Differences in the
riority because: (1) HFNC is a new therapy, (2) delaying nCPAP primary outcome were adjusted for SAS, gestational age groups,
may increase the risk of mechanical ventilation, and (3) the pos- and study center in a logistic regression model. Kaplan-Meier sur-
sible increased risk of infections. Assuming 5% attrition, we aimed vival analysis was performed for the differences in time to failure
to enroll 230 infants in each group. The study was stopped after a within 72 h of initiation of the support mode amongst the 2 study
planned interim analysis showed a significant difference (p < groups.
0.001) in the primary outcome between the 2 groups. Recruitment
of 272 infants was completed when the recommendations of the
interim analysis were available to us.
Results
Randomization
Randomization was stratified for SAS (>5 and ≤5) [11], gestation Among the 272 newborns enrolled in the study (Fig. 1),
in weeks (<31, 31–34, >34 weeks) and study center. Randomization 126 infants (46%) received surfactant (Table 1). Within
was computer generated and group assignment was placed in seri-
ally numbered, opaque, sealed envelopes that were opened by re- the first 72 h after birth, 46 of the 272 infants (17%) met
search personnel after entering the baby details on the outside cover. treatment failure criteria. The treatment failure was sig-
Due to the nature of intervention, blinding was not attempted. nificantly higher in the HFNC group (HFNC, n = 35/133,
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Table 1. Baseline characteristics of the
study participants Variable HFNC group nCPAP group p value
(n = 133) (n = 139)

Birth weight, g 1,632 ± 431 1,642 ± 437 0.83

Gestation, weeks 31.8 ± 1.9 31.6 ± 2.2 0.41
Gestation
28–30 weeks 30 (23) 46 (20)
31–34 weeks 87 (65) 79 (57) 0.15
35–36 weeks 16 (12) 27 (10)
Male 73 (55) 77 (55) 1.00
Singleton 83 (62) 75 (54) 0.18
Antenatal steroids
Complete 83 (62) 78 (56) 0.32
Partial 34 (26) 40 (29) 0.59
Delivery by Cesarean section 121 (91) 125 (90) 0.84
Apgar 1 min 7 (6–7) 7 (6–7) 0.77
Apgar 5 min 8 (7–8) 8 (7–8) 0.59
Age at randomization, h 0.5 (0.5–1.0) 0.5 (0.5–1.0) 0.32
SAS at randomization 5 (4–6) 5 (4–6) 0.44
SAS >5 at randomization 54 (41) 64 (46) 0.39
FiO2 at randomization 50 (30–50) 40 (30–50) 0.75
RDS 61 (54) 78 (42) 0.11

Data are presented as the mean ± SD, median (IQR), or n (%). Analysis was made by
2-sample t test, Mann-Whitney U test, or Fisher exact test as applicable.

26.3%, vs. nCPAP, n = 11/139, 7.9%, risk difference, RD,

Color version available online

1.0
of 18.4% and 95% CI 9.7–27.1, p < 0.0001). The unad-
justed odds ratio of 4.2 (95% CI 2.0–8.6, p < 0.0001) and
the adjusted odds ratio (adjusted for SAS, gestational age
0.8 groups and study center) of 5.0 (95% CI 2.3–10.8, p <
Proportion on primary support

0.0001) for the treatment failure was in favor of the

nCPAP group. The median time to treatment failure oc-
0.6 curred significantly later in the nCPAP group (Kaplan-
Meier survival analysis: HFNC group 3 h, nCPAP group
0.4
nCPAP 22 h, Mantel-Cox log-rank test p = 0.03; Fig. 2). Among
HFNC the infants in the HFNC group who had treatment failure
(n = 35), 32 were initially rescued with nCPAP and 3 were
0.2 intubated directly without a trial of nCPAP. Five (16%)
and 6 (19%) of the 32 infants in the HFNC group rescued
with nCPAP required subsequent ventilation in the first
0 3 and 7 days of birth, respectively. Protocol deviation was
0 10 20 30 40 50 60 70 80
recorded in 8 infants in each group. Excluding these 16
Time, h
patients (per protocol analysis), the treatment failure was
still significantly higher in the HFNC group (HFNC, n =
35/125, 28%, vs. nCPAP, n = 11/131, 8.4%; RD 19.6, 95%
Fig. 2. Kaplan-Meier survival curve for time to failure in the first
72 h.
CI 10.4–28.8, p < 0.0001). Among the subgroups of in-
fants with SAS >5 or ≤5 at randomization, the treatment
failure was also significantly higher in the HFNC group
(Table 2).
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Table 2. Primary outcome and need for mechanical ventilation

Variable HFNC group nCPAP group Risk difference, % p value

(n = 133) (n = 139) (95% CI)

Treatment failure within 72 h 35 (26.3) 11 (7.9) 18.4 (9.7 to 27.1) <0.0001

Ventilation within 3 days 8 (6.0) 11 (7.9) –1.90 (–7.9 to 4.1) 0.55
Ventilation within 7 days 9 (6.8) 13 (9.4) –2.6 (–9.0 to 3.9) 0.45
Time to treatment failure, h 3 (1–8) 22 (2–34) –19.0 (–1.9 to –36.1)a 0.04
Time to ventilation, h 21 (4.7–72.7) 19 (2.25–32.5) 2.0 (–46.1 to 50.1)a 0.32
Reasons for treatment failure
Increased oxygen need 16/35 (46) 3/11 (27) –18 (–49 to 13) 0.30
Increased respiratory distress 14/35 (40) 4/11 (36) –3.6 (–37 to 29) 0.84
Apnea 3/35 (8.6) 3/11 (27.3) –18.7 (–46.6 to 9.20) 0.16
Shock or other reasons 2/35 (5.6) 1/11 (9.1) –3.5 (–22.1 to 32.5) 0.69
Subgroup with SAS >5 54/133 (40.6) 64/139 (46.0) –5.4 (–17.2 to 6.3) 0.37
Treatment failure within 72 h 21/54 (38.9) 6/64 (9.4) 29.5 (14.6 to 44.3) 0.0003
Ventilation within 3 days 4/54 (7.4) 6/64 (9.4) –1.9 (–11.9 to 8.0) 0.72
Ventilation within 7 days 4/54 (7.4) 7/64 (10.9) –3.5 (–13.9 to –6.8) 0.54
Subgroup with SAS ≤5 79/133 (59.4) 75/139 (54.0) 5.4 (–6.3 to 17.2) 0.37
Treatment failure within 72 h 14/79 (17.7) 5/75 (6.7) 11.1 (0.9 to 21.2) 0.04
Ventilation within 3 days 4/79 (5.1) 5/75 (6.7) –1.6 (–9.0 to 5.8) 0.69
Ventilation within 7 days 5/79 (6.3) 6/75 (8.0) –1.7 (–9.8 to 6.5) 0.70
Subgroup of infants with gestation <32 weeks 58/133 (43.6) 68/139 (48.9) –5.3 (–17.1 to 6.5) 0.38
Treatment failure within 72 h 22/58 (37.9) 7/68 (10.3) 27.6 (13.2 to 42.1) 0.0002
Subgroup of infants with gestation ≥32 weeks 75/133 (56.4) 71/139 (51.1) 5.3 (–6.5 to 17.1) 0.38
Treatment failure within 72 h 15/75 (20.0) 6/71 (8.5) 11.5 (0.4 to 22.1) 0.05

Data are presented as n (%) or median (IQR). Analysis was by Fisher mid-p exact test or Mann-Whitney U test as applicable.
a Difference
between 2 medians and 95% CI.

Four infants in the HFNC group and 3 in the nCPAP Discussion

group died before discharge from hospital (Table 3). Six
of the 7 deaths occurred due to sepsis and 1 infant died of In this trial comparing HFNC with nCPAP for respira-
grade-IV IVH. The need for higher respiratory support tory distress in preterm infants, HFNC was inferior to
or intubation for surfactant was similar between the 2 nCPAP in preventing the failure of the support mode
groups (HFNC, n = 70/133, 53%, vs. nCPAP, n = 68/139, within the first 72 h of birth. The risk difference for treat-
49%, p = 0.54). The need for mechanical ventilation in the ment failure between the groups (18.4%) and the lower
first 3 or 7 days of life and the median time for the initia- limit of the confidence interval (9.7%) was greater than
tion of mechanical ventilation were similar between the 2 the inferiority margin of 5% in the entire group and also
groups. The most common reason for treatment failure in the subgroup of newborns with SAS >5 at enrolment
was increasing respiratory distress and an increase in ox- (RD 29.5%, 95% CI 14.6–44.3). However, when rescued
ygen requirement. The reasons for treatment failure, sur- with nCPAP for HFNC failures, the need for mechanical
factant therapy, the duration of respiratory support, du- ventilation is similar between the groups in the first 3 or
ration of oxygen, incidence of air leaks, and culture-pos- 7 days of life. The treatment failures within 72 h were
itive sepsis were similar between the groups. Nasal injury, higher with severe respiratory distress (SAS >5) and in
either mild (erythema), moderate, or severe (erosions or those with lower gestation, perhaps implying lower pres-
dilation of nares or columella damage), was comparable sure generation with HFNC than with nCPAP with the
between the groups. Time to reach full feeds, weights at settings used in either groups in this study.
hospital discharge, and the duration of hospitalization Reflecting our results, in the recent trial by Roberts et
were similar between the groups. al. [15], treatment failure occurred in 71 of the 278 infants
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Table 3. Secondary outcomes

Variable HFNC group CPAP group p value

(n = 133) (n = 139)

Mortality 4 (3.0) 3 (2.1) 0.71

Surfactant 58 (43.6) 68 (48.9) 0.38
Second dose of surfactant 18 (13.5) 24 (17.3) 0.40
Duration of respiratory support – CPAP or HFNC or ventilation, h 65 ± 99.9 69 ± 94.8 0.77
Duration of oxygen, h 99 ± 161.3 111 ± 141.8 0.53
Pneumothorax 0 1 (0.7) 1.00
HS-PDA 8 (6.0) 13 (9.4) 0.37
Culture positive sepsis 13 (9.8) 13 (9.4) 1.00
NEC Bell’s stage II or more 2 (1.5) 0 0.24
Nasal injury 7 (5.3) 13 (9.4) 0.25
Oxygen supplementation at 36 weeks 1 (0.7) 0 0.49
IVH grade III or IV 0 1 (0.7) 1.00
Cystic periventricular leukomalacia 0 1 (0.7) 1.00
ROP 6 (4.5) 7 (5.0) 1.00
Mean time to full feeds, days 5±4 5±3 0.59
Duration of hospitalization, days 18 ± 13 17 ± 14 0.95
Weight at hospital discharge, g 1,751 ± 413 1,737 ± 492 0.79

Data are presented as the mean ± SD or n (%). Analysis was by 2-sample t test or Fisher exact test as applicable.

(25.5%) in the HFNC group and in 38 of the 286 infants similar efficacy between the HFNC and nCPAP groups in
(13.3%) in the CPAP group (risk difference, 12.3 percent- their study.
age points, 95% CI 5.8–18.7, p < 0.001). Also, the risk dif- In a pilot trial comparing HFNC with NIPPV (nasal
ference of treatment failure was higher among infants intermittent positive pressure ventilation) for the prima-
with lower gestation (<32 weeks: 14.7%, 95% CI 4.8–24.7, ry treatment of RDS, HFNC was as effective as NIPPV in
vs. ≥32 weeks: 10.1%, 95% CI 2.2–18). However, the low- preventing endotracheal ventilation in premature infants
er limit of the confidence interval for treatment failure (gestation <35 weeks and birth weight >1,000 g) [5]. Sim-
was less than the non-inferiority margin chosen in that ilar to that trial, the need for higher respiratory support
trial (10%). Although both trials had similar methods, the or intubation for surfactant was similar in both the groups
noted differences were a higher age at randomization, use in our trial. In another trial that enrolled 85 preterm in-
of nCPAP prior to randomization, exclusion of infants fants (gestation 30–34 weeks) from August 2010 to Au-
requiring surfactant, lower median FiO2 at randomiza- gust 2013, on comparing HFNC with nCPAP as the pri-
tion (0.21–0.30), use of different devices for HFNC or mary treatment for respiratory distress, treatment failure
nCPAP, use of higher flows (maximum 8 LPM) and pres- (endotracheal intubation or mechanical ventilation) was
sures (maximum 8 cm), and a lower FiO2 criteria for seen in 16 out of 42 infants randomized to HFNC, and 9
treatment failures (FiO2 >0.40). out of 43 infants randomized to nCPAP (risk difference
In another trial that compared HFNC with nCPAP as 17.17 [−1.90 to 36.23], p = 0.099). This trial was not ad-
the primary respiratory support [16], among the 316 in- equately powered (power of 39%) to identify the risk dif-
fants enrolled the need for mechanical ventilation in the ference.
first 3 days of life (their primary outcome) was similar The proportion of infants with mortality, pneumotho-
between the 2 groups. Rescue nCPAP was not used for rax, and culture-positive sepsis remained the same be-
infants with treatment failure in the HFNC group. Com- tween the groups in our study and also in all other studies.
pared with our trial and that by Roberts et al. [15], enrol- As anticipated, nasal injury was reduced in the HFNC
ment of more mature infants (mean gestation of 33 group in our study and also in those by Roberts et al. [15]
weeks), infants with the less severe lung disease (median and Yoder et al. [17]. However, the severity of nasal in-
FiO2 at enrolment 0.23 to 0.25), and aggressive and excess jury in the nCPAP group in our study was lower than an-
use of surfactant in both groups may be the reasons for a ticipated.
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 A very early age of enrolment (0.5 h), the enrolment of the need for a higher mode of respiratory support in the
infants with severe lung disease (FiO2 at enrolment 0.40), first 72 h of life.
use of surfactant postrandomization, use of rescue nCPAP
for HFNC failure, and a higher FiO2 requirement for treat-
ment failure (0.60) are some the merits and unique features Acknowledgements
of this trial. Inability to blind the interventions, protocol
Dr. Sourabh Dutta and Dr. Deepak Chawla are acknowledged
deviations in 16 of 272 (5.8%) infants, and the premature
for interpreting the interim analysis and working as members of
termination of the trial are some of the limitations. Data Safety and Monitoring Board.

Conclusions Disclosure Statement

When comparing HFNC to nCPAP as a primary non- The authors have no financial relationship relevant to this ar-
invasive respiratory support in preterm infants with re- ticle or conflicts of interests to disclose
spiratory distress, HFNC is inferior to nCPAP in avoiding

References
  1 Gupta N, Saini SS, Murki S, Kumar P, Deora-   6 Shin J, Park K, Lee EH, Choi BM: Humidified 12 Walsh MC, Kliegman RM: Necrotizing en-
ri A: Continuous positive airway pressure in high flow nasal cannula versus nasal continu- terocolitis: treatment based on staging crite-
preterm neonates: an update of current evi- ous positive airway pressure as an initial re- ria. Pediatr Clin North Am 1986;33:179–201.
dence and implications for developing coun- spiratory support in preterm infants with re- 13 Papile LA, Burstein J, Burstein R, Koffler H:
tries. Indian Pediatr 2015;52:319–328. spiratory distress: a randomized, controlled Incidence and evolution of subependymal
  2 Kandraju H, Murki S, Subramanian S, Gad- non-inferiority trial. J Korean Med Sci 2017; and intraventricular hemorrhage: a study of
dam P, Deorari A, Kumar P: Early routine 32:650–655. infants with birth weights less than 1,500 gm.
versus late selective surfactant in preterm ne-   7 Yoder BA, Stoddard RA, Li M, King J, Dirn- J Pediatr 1978;92:529–534.
onates with respiratory distress syndrome on berger DR, Abbasi S: Heated, humidified 14 de Vries LS, Eken P, Dubowitz LM: The spec-
nasal continuous positive airway pressure: a high-flow nasal cannula versus nasal CPAP trum of leukomalacia using cranial ultra-
randomized controlled trial. Neonatology for respiratory support in neonates. Pediatrics sound. Behav Brain Res 1992;49:1–6.
2013;103:148–154. 2013;131:e1482–e1490. 15 Roberts CT, Owen LS, Manley BJ, Frøisland
  3 Rojas MA, Lozano JM, Rojas MX, Laughon  8 Roberts CT, Manley BJ, Dawson JA, Davis DH, Donath SM, Dalziel KM, et al: Nasal
M, Bose CL, Rondon MA, et al: Very early sur- PG: Nursing perceptions of high-flow nasal high-flow therapy for primary respiratory
factant without mandatory ventilation in pre- cannulae treatment for very preterm infants. support in preterm infants. N Engl J Med
mature infants treated with early continuous J Paediatr Child Health 2014;50:806–810. 2016;375:1142–1151.
positive airway pressure: a randomized, con-   9 Collins CL, Holberton JR, Barfield C, Davis 16 Lavizzari A, Colnaghi M, Ciuffini F, Veneroni
trolled trial. Pediatrics 2009;123:137–142. PG: A randomized controlled trial to compare C, Musumeci S, Cortinovis I, et al: Heated,
  4 Hough JL, Shearman AD, Jardine LA, Davies heated humidified high-flow nasal cannulae humidified high-flow nasal cannula versus
MW: Humidified high flow nasal cannulae: with nasal continuous positive airway pres- nasal continuous positive airway pressure for
current practice in Australasian nurseries, a sure postextubation in premature infants. J respiratory distress syndrome of prematurity:
survey. J Paediatr Child Health 2012;48:106– Pediatr 2013;162:949–954.e1. a randomized clinical noninferiority trial.
113. 10 Manley BJ, Owen LS, Doyle LW, Andersen JAMA Pediatr 2016, DOI: 10.1001/jamapedi-
  5 Kugelman A, Riskin A, Said W, Shoris I, Mor CC, Cartwright DW, Pritchard MA, et al: atrics.2016.1243.
F, Bader D: A randomized pilot study com- High-flow nasal cannulae in very preterm in- 17 Yoder BA, Stoddard RA, Li M, King J, Dirn-
paring heated humidified high-flow nasal fants after extubation. N Engl J Med 2013;369: berger DR, Abbasi S: Heated, humidified
cannulae with NIPPV for RDS. Pediatr Pulm- 1425–1433. high-flow nasal cannula versus nasal CPAP
onol 2015;50:576–583. 11 Silverman WA, Andersen DH: A controlled for respiratory support in neonates. Pediatrics
clinical trial of effects of water mist on ob- 2013;131:e1482–e1490.
structive respiratory signs, death rate and nec-
ropsy findings among premature infants. Pe-
diatrics 1956;17:1–10.
161.132.207.49 - 7/29/2019 12:12:02 AM

HFNC versus nCPAP for Respiratory Neonatology 2018;113:235–241 241

Universidad Peruana Cayetano

Support in Preterm Infants DOI: 10.1159/000484400

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