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Noninvasive Ventilation Strategies for

Early Treatment of RDS in Preterm


Infants: An RCT
Vincenzo Salvo, MDa, Gianluca Lista, MDb, Enrica Lupo, MDb, Alberto Ricotti, MDc, Luc J.I. Zimmermann, MD, PhDd,
Antonio W.D. Gavilanes, MDd,e, Ignazio Barberi, MD, PhDa, Micaela Colivicchi, MDc, Francesca Temporini, MDc,
Diego Gazzolo, MD, PhDc

abstract BACKGROUND AND OBJECTIVES: There is evidence that new methods of noninvasive ventilation (NIV) support have
signicantly changed respiratory distress syndrome (RDS) management in preterm infants. Further
perspectives for neonatologists involve the assessment of different NIV strategies in terms of availability,
effectiveness, and failure. This study evaluates the efcacy of 2 different NIV strategies for RDS treatment in
very low birth weight (VLBW) infants: nasal synchronized intermittent positive pressure ventilation (NSIPPV),
which is a modality of conventional ventilation with intermittent peak inspiratory pressure, and bilevel
continuous positive airway pressure (BiPAP), not synchronized, with 2 alternate levels of continuous positive
airway pressure.
METHODS: We conducted a 2-center randomized control study in 124 VLBW infants (,1500 g and ,32 weeks of
gestational age) with RDS who received NIV support (NSIPPV, n = 62; BiPAP, n = 62) within 2 hours of birth. We
evaluated the performance of NIV strategies by selected primary outcomes (failure rate and duration of
ventilation) and secondary outcomes.
RESULTS: The number of failures and duration of ventilation support did not differ between NSIPPV and BiPAP
strategies (P . .05 for both). Moreover, no differences between groups were found regarding secondary
outcomes (P . .05 for all).
CONCLUSIONS: The present data show no statistically signicant differences between NSIPPV and BiPAP
strategies in terms of duration of ventilation and failures, suggesting that both NIV techniques are effective in
the early treatment of RDS in VLBW infants. Further randomized investigations on wider populations are
needed to evaluate the effect of NIV techniques on long-term outcomes.

WHATS KNOWN ON THIS SUBJECT: Noninvasive a


Neonatal ICU, G. Martino University Hospital of Messina, Italy; bNeonatal ICU, V. Buzzi Childrens Hospital, Milan,
Italy; cNeonatal ICU, C. Arrigo Childrens Hospital, Alessandria, Italy; dDepartment of Pediatrics and Neonatology,
ventilation (NIV) reduced the need of intubation in School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht,
preterm infants with RDS. However, randomized Netherlands; and eInstitute of Biomedicine, Catholic University of Guayaquil, Ecuador
studies comparing nasal synchronized Dr Salvo designed the study, participated in patient recruitment, data analysis, and writing the
intermittent positive pressure ventilation and manuscript, and submitted the nal version; Dr Lista designed the study and participated in patient
bilevel continuous positive airway pressure are recruitment, data collection, and writing the manuscript; Dr Lupo participated in patient
recruitment, data collection, and writing the manuscript; Dr Ricotti participated in the design of the
still lacking. project, patient recruitment, and writing the manuscript; Dr Zimmermann supervised project
WHAT THIS STUDY ADDS: The present study design and data collection and participated in writing the manuscript; Drs Gavilanes and Barberi
supervised project design and participated in writing the manuscript; Drs Colivicchi and Temporini
shows no differences in short-term outcomes participated in patient recruitment and data collection and analysis; Dr Gazzolo (project leader)
between 2 different NIV strategies, nasal participated in data analysis and wrote the manuscript. All authors approved the nal manuscript
synchronized intermittent positive pressure as submitted and agree to be accountable for all aspects of the work.

ventilation and bilevel continuous positive airway This trial has been registered at www.clinicaltrials.gov (identier NCT02259400).
pressure, in preterm infants for the initial www.pediatrics.org/cgi/doi/10.1542/peds.2014-0895
treatment of RDS. DOI: 10.1542/peds.2014-0895
Accepted for publication Dec 8, 2014
Address correspondence to Diego Gazzolo, MD, PhD, NICU, C. Arrigo Childrens Hospital, Spalto
Marengo 46, 15100 Alessandria, Italy. E-mail: dgazzolo@hotmail.com

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ARTICLE PEDIATRICS Volume 135, number 3, March 2015
In recent decades, considerable elucidating any differences between The protocol for delivery room
changes have been made in the NSIPPV and BiPAP, used as the management, RDS treatment, devices
management of respiratory distress primary mode of ventilation for RDS, and interfaces used, and ventilator
syndrome (RDS), supporting the are yet available, except for adjustment were the same for the 2
notion that appropriate perinatal a nonrandomized study.13 centers. Infants who had signs of RDS
management can be effective by Therefore, the present randomized at birth were treated with sustained
minimizing the use of mechanical study aimed to investigate the lung ination (SLI)14 and NCPAP in
ventilation (MV) in very low birth effectiveness of these 2 different NIV addition to the American Academy of
strategies: NSIPPV, synchronized with Pediatrics recommendations.15
weight (VLBW) infants. In particular,
antenatal steroid prophylaxis, an intermittent positive pressure, and The respiratory strategy for RDS
accurate delivery room and BiPAP, nonsynchronized with 2 treatment in the newborns was as
respiratory management with early alternate levels of continuous positive follows. In the delivery room, after
nasal continuous positive airway airway pressure (CPAP), as the oropharyngeal and nasal suctioning,
pressure (NCPAP), surfactant primary mode of ventilation in the pressure-controlled SLI (25 cmH2O)
replacement in the early phase of respiratory management of RDS in was performed for 15 seconds using
VLBW infants in terms of duration a neonatal mask and a T-piece
RDS, the INSURE (intubation,
and failure of NIV support and of ventilator (Neopuff Infant T-Piece
surfactant extubation) procedure, and
selected secondary outcomes. Resuscitator, Fisher & Paykel,
the increased use of noninvasive
ventilation (NIV) have been shown to Auckland, New Zealand), followed by
improve respiratory outcome.15 the delivery of 5 cmH2O NCPAP.16
METHODS The SLI maneuver was repeated in
The hypothetical advantages of NIV, We conducted a randomized study in patients in whom respiratory and/or
compared with invasive MV, consist 124 VLBW infants, admitted in 2 heart failure persisted. After failure of
in the possibility to reduce NICUs (C. Arrigo, Childrens Hospital, the second SLI maneuver, infants
barotrauma, biotrauma, and Alessandria, Italy, and V. Buzzi, were intubated. In both groups,
ventilator-induced lung injury. Data Childrens Hospital, Milan, Italy) from neonatal care was started at the
on NIV support, such as nasal January 2010 to December 2012, lowest oxygen concentration,
intermittent positive pressure delivered before 32 weeks of between 0.21 and 0.4 fraction of
ventilation (NIPPV), nasal gestational age (wGA) with a birth inspired oxygen (FIO2), to maintain
synchronized intermittent positive weight ,1500 g (Fig 1). Approval arterial oxygen saturation (SaO2) of
pressure ventilation (NSIPPV), and was obtained from the respective 85% to 93%. All enrolled infants
bilevel continuous positive airway local ethics committees. Informed and were transferred to the NICU with
pressure (BiPAP), are still written consent was obtained, before NCPAP support (5 cmH2O). Further
controversial. On the one hand, delivery, from all parents of the support depended on gestational
NSIPPV/NIPPV has shown promising patients before inclusion in the study. age (GA):
short- and long-term respiratory
outcomes compared with NCPAP or
MV.610 On the other hand, Kirpalani
et al found no signicant differences
between NCPAP and NIV strategies
(ie, NSIPPV/NIPPV/BiPAP) in a wider
study population, in terms of
mortality or occurrence of
bronchopulmonary dysplasia
(BPD).11 In this regard, Roberts et al
described several discrepancies
among studies previously conducted
(ie, recruited populations, ventilation
modalities, devices used,
synchronization systems, and clinical
applications) and concluded that, at
this stage, no clear advantages were
detectable for NIPPV or BiPAP over
NCPAP in reducing mortality or FIGURE 1
BPD.12 Moreover, no studies Flow chart describing recruitment.

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PEDIATRICS Volume 135, number 3, March 2015 445
1. Newborns #26 wGA received ventilator parameters were lower and with a reduction of RR to 15 breaths
a prophylactic replacement of higher, CPAP levels 4 to 6 cmH2O and per minute with a PIP of 10 to
surfactant with INSURE in the rst 8 to 9 cmH2O, respectively; a timehigh 15 cmH2O and a PEEP of 4 cmH2O and
2 hours of life. After INSURE, the of 1 second; and a pressure exchange was stopped when infants showed no
infants were switched to either rate of 20/minute, with the lowest signs of RDS with FIO2 ,0.30.
BiPAP or NSIPPV. adjusted FIO2 to maintain an SaO2 of
88% to 93%. Respiratory settings Failure Criteria
2. Newborns .26 and #29 wGA re-
ceived BiPAP or NSIPPV in the rst (CPAP lower maximum 7 cmH2O, NIV failure was dened when 1 or
2 hours of life. CPAP higher maximum 10 cmH2O, more of the following criteria
pressure exchange rate max 30/ persisted or recurred, after
3. Newborns .29 wGA not requiring
minute) were adjusted to guarantee a surfactant dose (maximum 3 doses)
or positively responding to the
blood gas analysis within normal or within 12 hours from previous
initial resuscitation maneuver
ranges. Weaning was started with administration: (1) hypoxia (FIO2
were maintained on NCPAP sup-
a progressive reduction of the set requirement .0.40), (2) acidosis
port until arrival at the NICU; after
pressure exchange rate (minimum 15 (pH ,7.20) and hypercarbia
2 hours from birth, if they did not
pressure exchanges/minute), (PCO2 .65 mm Hg), and (3) apnea as
show any signs of RDS, NCPAP was
followed by a reduction of the higher $4 episodes/hour or the need for
stopped. BiPAP/NSIPPV was per-
CPAP level to 6 cmH2O and the lower mask ventilation $2 times/hour.
formed if clinical and blood gas
CPAP level to 4 cmH2O. BiPAP was We also considered necrotizing
analysis patterns were suggestive
stopped when infants showed no enterocolitis (NEC), bowel perforation,
of RDS as follows: (a) need of
signs of RDS with FIO2 ,0.30. and hemodynamic instability
FIO2 .0.4 and/or (b) pH ,7.20
conditions for NIV failure.18
and/or PO2 ,50 mm Hg and/or
NSIPPV
PCO2 .65 mm Hg and (c) clinical Surfactant Administration
patterns of RDS characterized by NSIPPV support was delivered with
a nasal ventilator device (Giulia, According to the protocol of
retractions and/or dyspnea. Apnea,
respiratory management, the rst
dened as $4 episodes/hour Ginevri, Rome, Italy) that detects the
inspiratory effort by means of dose of surfactant was administered at
or need for mask ventilation
200 mg/kg (Curosurf, Chiesi, Parma,
$2 times/hour, was another a pneumotachograph equipped with
a xed orice (2-mm diameter for low Italy). Additional doses of surfactant
criterion to start NIV support.
birth weight infants). This is were given at 100 mg/kg, at least
Newborns complicated by RDS 12 hours after previous administration.
a conventional strategy of
requiring NIV support within 2 hours After INSURE, newborns received the
synchronized ventilation provided by
from birth but not intubated were same NIV support device as before.
nasal interface, with short binasal
allocated by use of computer-
prongs (NIV set, Ginevri, Rome, Italy) All newborns were treated with
generated random numbers to receive
of different sizes according to weight. caffeine (caffeine citrate 20 mg/kg
either NSIPPV (n = 62) or BiPAP
The inspiratory ow was detected as loading dose; 5 to 10 mg/kg/day
(n = 62). Apneic or severely depressed
a pressure change across the maintenance).
newborns requiring MV within
resistance, positioned proximally to
2 hours from birth were excluded Monitoring Parameters
the nasal interface. The initial
from the study and started on MV.17
ventilator parameters were positive- Newborns were monitored by using
end expiratory pressure (PEEP) 4 to pre-postductal SaO2 monitoring
BiPAP 6 cmH2O; peak inspiratory pressure (Masimo Datascope Radical, Masimo
BiPAP support was delivered using (PIP) 15 to 20 cmH2O; inspiratory Corporation, Irvine, CA). For each
the Infant Flow-driver device (Infant time 0.3 to 0.4 second; ow rate 6 to infant, the following variables were
Flow System, Viasys Corp, Yorba 10 L/minute; respiratory rate (RR) 40 recorded: GA, BW, gender, main
Linda, CA). We used the short binasal breaths per minute with the lowest maternal pregnancy diseases, mode
prongs as interface (CareFusion, adjusted FIO2, to maintain an SaO2 of of delivery, and Apgar scores at 1 to
Yorba Linda, CA) with different sizes 88% to 93%. Respiratory settings (PIP 5 minutes. At study entry, FIO2, mean
according to weight. This method of maximum 25 cmH2O, PEEP maximum airway pressure (MAP), SaO2, pH, and
nonsynchronized ventilation support 7 cmH2O, RR maximum 60 breaths per PCO2 were recorded.
provides 2 alternate levels, lower and minute) were adjusted to guarantee
higher, of CPAP; the newborn can blood gas analysis within normal Primary Outcomes
breathe spontaneously on these 2 ranges. The highest trigger sensitivity The primary end points were the
levels to create 2 different functional avoiding autotriggering was selected. duration of NIV support and failure
residual capacities (FRCs). The initial Weaning from NSIPPV was performed rate.

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446 SALVO et al
Secondary Outcomes P ,.05 was considered statistically Table 2 shows primary and
Secondary end points were duration signicant, and all P values were secondary outcome characteristics.
of respiratory support, incidence of based on 2-tailed tests. Statistical No signicant differences were found
pneumothorax (PNX), occurrence of analysis was performed by using SPSS between groups in terms of duration
moderate/severe BPD, incidence for Windows (SPSS, Chicago, IL). of ventilation on NIV support and
of intraventricular hemorrhage incidence of failure. Moreover, there
(IVH) more than second degree, were no signicant differences in the
periventricular leukomalacia (PVL), RESULTS incidence of postnatal death,
need for second/multiple surfactant Table 1 shows the perinatal moderate/severe BPD, PNX, IVH, PVL,
doses, need for postnatal characteristics in the studied groups. postnatal glucocorticoid
glucocorticoid treatment, persistence No signicant differences (P . .05) administration, multiple surfactant
of patent ductus arteriosus (PDA) were found between NSIPPV and doses, PDA, ROP, NEC, LOS, or time to
requiring pharmacological treatment, BiPAP groups for wGA, BW, gender, regain BW. PNX occurred in 6 cases
retinopathy of prematurity (ROP) incidence of cesarean delivery, (NSIPPV, n = 2; BiPAP, n = 4) and
more than second degree, NEC, late- premature rupture of membranes, represented a cause of NIV failure in
onset sepsis (LOS), death, and days to evidence of chorioamnionitis, 3 cases (NSIPPV, n = 2; BiPAP, n = 1).
regain BW. Moderate/severe BPD occurrence of pregnancy In 18 of 124 infants (NSIPPV, n = 10;
was dened according to the hypertension requiring BiPAP, n = 8), NIV support failed.
classication of Jobe and Bancalari,19 antihypertensive agent treatment, The causes were early-onset sepsis
IVH was classied according to Papile abruptio placentae, occurrence of (NSIPPV, n = 5; BiPAP, n = 3),
et al,20 and ROP was graded multiple pregnancies, complete pulmonary hypertension (NSIPPV,
according to the criteria established course of prenatal glucocorticoids n = 5; BiPAP, n = 4), hypoxia and
by the International Committee for prophylaxis, and Apgar scores at hypercapnia (NSIPPV, n = 2; BiPAP,
Classication of ROP.21 1 and 5 min. No differences were n = 4), hypoxia alone (NSIPPV, n = 3;
shown regarding blood gas analysis, BiPAP, n = 3), PDA (NSIPPV, n = 1),
Statistical Analysis FIO2, SaO2, pH, and PCO2 at study entry. NEC (BiPAP, n = 2), and PNX
For the calculation of sample size, we We observed a signicant difference (NSIPPV, n = 2; BiPAP, n = 1). The
used duration of ventilation as the in MAP that was higher in the NSIPPV timing of NIV failure did not differ
main primary outcome. As no basic group than the BiPAP group, between studied groups (median
data are available for this high-risk depending on the initial ventilator [25th to 75th centile] for NSIPPV,
population, we were able to retrieve settings. 36 hours [17 to 72]; for BiPAP, 34
the duration of ventilation by the 2
different NIV strategies from the
database of our 2 NICUs. These data TABLE 1 Perinatal Characteristics of Preterm Infants Supported by NSIPPV or BiPAP
were used for the power calculation. NSIPPV (n = 62) BiPAP (n = 62) P
We assumed a difference of 24 hours BW, g 1106 6 276 1165 6 275 .23
between the 2 groups in the duration GA, wks 28.6 6 2.1 28.8 6 2.2 .66
of NIV as clinically relevant. At GA #26 wks 9 9 .999
a condence level a = 0.05 and power GA .26 and #29 wks 33 32 .999
GA .29 wks 20 21 .999
level of 0.80, we needed 62 patients Male/female 27/35 25/37 .85
for each group.22 The sample size was Small for GA 14 12 .82
calculated by using nQuery Advisor Cesarean delivery 38 47 .12
(Statistical Solutions, Saugus, MA), Preterm premature rupture of membrane 13 20 .22
version 5.0. Chorioamnionitis 10 12 .63
Pregnancy-induced hypertension requiring 13 20 .22
Data were reported as means and SD treatment with antihypertensive agents
and median and interquartile ranges Abruptio placentae 10 10 .999
for continuous variables, whereas Twins 10 15 .37
Prenatal steroids completed course 55 57 .76
absolute and relative frequencies Apgar score at 1 min 761 76 1 .999
were used for categorical variables. Apgar score at 5 min 861 86 1 .999
SaO2 at study entry, % 86 6 12 87 6 14 .67
Parameters of the 2 groups were
FIO2 requirement at study entry 0.32 6 0.04 0.35 6 0.05 .78
compared using Student t or Mann- MAP at study entry, cmH2O 7.6 6 1.0 6.2 6 1.2 ,.01
Whitney U 2-sided tests for pH at study entry 7.21 6 0.15 7.23 6 0.10 .38
continuous variables and x2 or Fisher pCO2 at study entry, mmHg 54 6 9 53 6 8 .51
exact test for categorical variables. Data are presented as the mean 6 SD or n.

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PEDIATRICS Volume 135, number 3, March 2015 447
TABLE 2 Primary and Secondary Outcomes in Preterm Infants Supported by NSIPPV or BiPAP additional support to a previous
NSIPPV (n = 62) BiPAP (n = 62) P nonrandomized observation using
Primary outcomes
NSIPPV and BiPAP as primary modes
Nasal ventilation support, h 89 (61143) 87 (48134) .45 in the treatment of RDS.13 In our
Failure of nasal ventilation support 10 8 .80 series, we also found a low incidence
Secondary outcomes of failure (18 of 124 newborns, 15%)
Death 0 2 .49 and a brief time of respiratory
Moderate/severe BPD 7 7 (n = 60) 1.00
PNX 2 4 (n = 60) .43
support (median for NSIPPV 89
IVH .2nd degree 2 2 (n = 60) 1.00 hours; for BiPAP 87 hours). Moreover,
PVL 2 4 (n = 60) .43 no correlations were found between
Postnatal glucocorticoids 5 5 (n = 60) 1.00 failure occurrences and GA
PDA 18 14 (n = 60) .54 subgroups.
ROP .2nd degree 2 3 (n = 60) .68
NEC 0 2 (n = 60) .49 Low failure in NIV support can be
Multiple surfactant doses 21 18 (n = 60) .97 also explained on the basis of
Surfactant, .26 wGA 19 (n = 53) 21 (n = 52) .78
perinatal treatments, such as prenatal
Early-onset sepsis 13 15 (n = 60) .67
LOS 21 14 (n = 60) .23 glucocorticoid prophylaxis (85% to
Time to regain BW, d 14 6 4 13 6 4 .17 90% for our population), known to be
Data are presented as the median (25th to 75th centile), n, or mean 6 SD. effective on lung immaturity, and
improvements in delivery room
management such as SLI and early
hours [19 to 65]) (P . .05) have considerably changed RDS NCPAP. Recent observations reported
(Table 3). treatment in VLBW infants. New an improved postnatal adaptation, in
We did not nd statistically delivery room management and early terms of lung and cardiovascular
signicant differences in the NIV support signicantly contributed function, in SLI-treated infants and
incidence of failure either between to a sensible decay in the need for MV animals.29,30 Another explanation can
the 2 study groups (P . .05 for all) or support.2328 Thus, further be the early NCPAP support in the
between failure subgroups after perspectives for neonatologists delivery room, which is known to be
stratication for wGA (Table 3). In involve the assessment of different benecial for lung outcome.2,2328
addition, infants who failed did not NIV strategies in terms of availability,
effectiveness, and failure. Although the current study shows
signicantly differ in baseline
that both methods of NIV (SIPPV and
characteristics from infants who did In the present 2-center randomized BiPAP) are feasible and probably
not fail on NIV. study, we found no differences in equally effective, it does not answer
primary and secondary end points the question whether NIV is better
between 2 different NIV strategies
DISCUSSION than NCPAP as primary treatment of
(ie, NSIPPV and BiPAP) performed as
RDS. Several authors in smaller study
In the last decade, new therapeutic primary modes for RDS treatment.
populations (NIPPV or BiPAP versus
strategies and technological advances Results are consistent and offer
NCPAP) and a meta-analysis reported
less need of MV, less risk of
TABLE 3 Characteristics, Timing, and Causes of Failure of Preterm Infants Who Failed on NIV
intubation in the rst 72 hours from
NSIPPV (n = 10) BiPAP (n = 8) P
birth, and reduction of hospitalization
BW, g 1000 6 310 980 6 268 .92 duration and O2 dependency.7,10,3133
GA, wks 28 6 1 28 6 1 .93
However, Kirpalani et al, in a recent
GA #26 wks/total GA subgroup 2/9 2/9 1.00
GA .26 and #29 wks/total GA subgroup 7/33 4/32 .54 large multicenter trial, showed no
GA .29 wks/total GA subgroup 1/20 2/21 .96 signicant differences in terms of
Apgar score at 1 min 661 661 1.00 mortality or BPD occurrence between
Apgar score at 5 min 861 861 1.00 NCPAP and NIV strategies, used both
Prenatal steroids completed course 7 6 .77
Timing of failure (median, 25-75 centile), h 36 (1772) 34 (1965) .83 as rst intention or in the weaning
Early-onset sepsis 5 3 .96 phase, but without a specic protocol
Hypoxemia 3 3 .87 for NIV (devices, modalities,
Hypercapnia and hypoxemia 2 4 .32 synchronization).11 Finally, Roberts
Persistent pulmonary hypertension of the newborn 5 4 1.00
PNX 2 1 1.00
et al suggested that NIPPV
PDA 1 0 1.00 (synchronized or nonsynchronized)
NEC 0 2 .47 might be advantageous over NCPAP
Data are presented as the mean 6 SD, n, or median (25th to 75th centile). as primary support for reduction of

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448 SALVO et al
intubation, although there is no clear pressure from the set pressure, denite conclusions. In this respect,
advantage.12 increase in VT and minute ventilation, we observed a moderate/severe BPD
On the basis of the present ndings, and the drop in work of incidence, comparable to that of
bearing in mind that NIV strategies breathing.3943 Therefore, further previous studies.38,46 The low
can act through different modalities, studies are needed to evaluate the incidence of PNX, NEC, or bowel
further investigations evaluating their transmission of setting pressures to perforations suggests that NIV
effectiveness in RDS treatment are the lower airways in an open system techniques could be considered
justied.34 Indeed, NSIPPV uses with large and variable leakage and reasonably safe for these infants.
a conventional synchronized modality improve NIV synchronization systems Last but not least, successful NIV
of intermittent positive pressure with infant spontaneous breathing. management requires a high quality
ventilation, delivered through a nasal However, we found no difference in of neonatal care. High-risk infants
interface, whereas BiPAP uses effectiveness between nasal-ow require experienced nurses for the
a nonsynchronized ventilation that synchronized (NSIPPV) and best cleaning of the upper airways,
provides alternately 2 different CPAP nonsynchronized (BiPAP) strategies. nasal cannula positioning, and
levels without intermittent peak of Data on prophylactic/early surfactant maintaining the containment position
inspiratory pressure, in which administration available at the time of of the newborns. These precautions
newborns can breathe spontaneously, patient recruitment were still are implemented to ensure effective
creating 2 different FRCs. Both controversial and under debate. airow, maintaining adequate
methods have theoretical benets. In Therefore, in infants #26 wGA, we pressure from the nostrils to the
particular, (1) NSIPPV through chose prophylactic surfactant distal airways, to increase comfort of
intermittent increase in pressure administration (ie, within 2 hours the newborns and prevent trauma
enhances tidal volume (VT), minute from birth, after stabilization on to the nostrils.47
ventilation, and MAP, resulting in NCPAP) for the higher risk of
better alveolar recruitment and gas failure,23 whereas a selective
exchange9,12,35; (2) BiPAP, by using CONCLUSIONS
therapeutic strategy was planned for
a much longer timehigh, permits those .26 wGA.44 Currently, The present data show that both
a complete respiratory cycle prophylactic approaches do not seem NSIPPV and BiPAP, used as primary
(inspiration and expiration) on the to be justied, and further respiratory support in the treatment
higher CPAP level, creating 2 different investigations to clarify the efcacy of of RDS of VLBW infants, are feasible
FRCs; increases MAP; and FRC early NIV with the best timing for and equally effective. These results
switching generates a VT with better surfactant administration, especially prompt further RCT investigations to
gas exchange.7,36 Additional common in extremely low birth weight infants, evaluate the effectiveness of different
NIV advantages, due to pressure are eagerly awaited.45 We did not nd NIV strategies on long-term outcomes.
changes, consist in the stimulation of any differences between groups in the
spontaneous breathing that reduces need for surfactant single/multiple
failure risk due to apneas.37 Another ACKNOWLEDGMENTS
doses.
issue deserving further consideration This study is part of the Italia Olanda
concerns NIV settings. On the one In the present series, we found no PhD International Program, under the
hand, several authors highlight the statistically signicant differences in auspices of the Italian Society of
need for strict protocols and secondary outcomes between the 2 Neonatology and of the Neonatal
guidelines638; on the other hand, NIV devices. Of course, the small Clinical Biochemistry Research Group,
there is still no consensus, since number of infants eligible for and was partially supported by grants
conicting results have been reported statistical analysis of secondary to DG from I Colori della Vita
in terms of variability of airway outcomes does not allow us to draw Foundation, Italy.

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).


Copyright 2015 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: Prof Zimmermann has received payments from Chiesi BV and AbbVie BV for lectures in industry sponsored symposia or workshop,
indirectly related to the topic of this paper; the other authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Prof Zimmermann has received payments from Chiesi BV and AbbVie BV for lectures in industry-sponsored symposia or
workshops, indirectly related to the topic of this paper; the other authors have indicated they have no potential conicts of interest to disclose.

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PEDIATRICS Volume 135, number 3, March 2015 449
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PEDIATRICS Volume 135, number 3, March 2015 451
Noninvasive Ventilation Strategies for Early Treatment of RDS in Preterm
Infants: An RCT
Vincenzo Salvo, Gianluca Lista, Enrica Lupo, Alberto Ricotti, Luc J.I. Zimmermann,
Antonio W.D. Gavilanes, Ignazio Barberi, Micaela Colivicchi, Francesca Temporini
and Diego Gazzolo
Pediatrics 2015;135;444; originally published online February 9, 2015;
DOI: 10.1542/peds.2014-0895
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Services /content/135/3/444.full.html
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
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Noninvasive Ventilation Strategies for Early Treatment of RDS in Preterm
Infants: An RCT
Vincenzo Salvo, Gianluca Lista, Enrica Lupo, Alberto Ricotti, Luc J.I. Zimmermann,
Antonio W.D. Gavilanes, Ignazio Barberi, Micaela Colivicchi, Francesca Temporini
and Diego Gazzolo
Pediatrics 2015;135;444; originally published online February 9, 2015;
DOI: 10.1542/peds.2014-0895

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/135/3/444.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2015 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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