1Head of the Neonatal Intermediate Care Unit, Instituto Nacional de Perinatología, México
2Neonatology Department, Instituto Nacional de Perinatología, México
3Respiratory Support Group, México
Submission: March 10, 2017; Published: June 01, 2017
*Corresponding author: Echániz Avilés MOL, Neonatology Department, Instituto Nacional de Perinatología, Calle Montes Urales 800, Miguel Hidalgo, Lomas Virreyes, 11000 Ciudad de México, CDMX, Mexico.
How to cite this article: Romero-M S, Hernández-R M, Pérez-V M, López-P M. Bubble CPAP versus Variable Flow CPAP in Preterm Newborns with
Respiratory Distress: A Randomized Controlled Trial . Acad J Ped Neonatol. 2017; 4(5): 555704. DOI: 10.19080/AJPN.2017.04.555704
Objective: To assess the efficacy and safety of continuous positive airway pressure using variable flow (VF) against nasal bubble continuous positive airway pressure (nCPAP).
Methods: Between August 2011 and November 2012, one hundred and one preterm newborns, less than 34 weeks gestational age with RDS requiring CPAP were randomly assigned to two study groups: 47 to the VF and 54to the nCPAP group. CPAP failure, presence of air leaks, hyperemia of nasal mucosa and need for mechanical ventilation were recorded, of, as well as associated morbidities such as Intraventricular hemorrhage (IVH), Necrotizing Enterocolitis (NEC), pneumonia, Bronchopulmonary dysplasia (BPD) and Patent Ductus Arteriosus (PDA). Categorical outcome variables were tested using the chi-square test or Fisher’s exact test. Continuous variables were analyzed using Student’s t-test or the Mann-Whitney test. Level of significance was set at p<0.05.
Results:CPAP failure was reported in 23% of VF and 17% for nCPAP (p = 0.39). Air leak syndrome occurred in 3.7% for nCPAP and 4.3% for VF (p=0.88), and hyperemia of the nasal mucosa was 5.6% for nCPAPvs 12.8% for VF (p=0.20).
Conclusion: In newborns <34 weeks’ gestational age and moderate RDS, the use of continuous flow nCPAP showed the same benefits as variable flow nCPAP.
The World Health Organization (WHO) reports 15 million preterm newborns per year [1,2]. Respiratory distress is one of the main causes of perinatal morbidity and mortality. The incidence of respiratory distress syndrome (RDS) is 10% among preterm newborns in our hospital’s Intermediate Care Unit. The Instituto Nacional de Perinatología is a tertiary-level hospital, where 300 preterm infants with <1500g birth weight are taken care of and more than 500 nCPAP devices are used each year .
Continuous positive airway pressure (CPAP) has been widely used to manage RDS in newborn infants [4,5]. The clinical goals
of CPAP are to maintain the functional residual capacity (FRC)
of the lungs and support gas exchange to reduce apnea, work of breathing (WOB) and lung injury [6,7]. The Infant Flow Driver (IFD) device consists of a flow driver which provides a continuous blended gas source and an airway pressure monitoring system. Experimental data have shown that IFD is capable of providing a consistent airway pressure and has also been shown to impose a lower WOB than other devices that use fluidic control to maintain CPAP [8,9].
In our Institution we started to use IFD in 2011 and had few clinical data to evaluate its superiority over nasal bubble CPAP. Therefore, to compare both types of respiratory devices, a
randomized clinical trial was conducted to assess their efficacy
and safety in our Institution.
One hundred and twenty newborns less than 34 weeks’
gestational age who were admitted to the intermediate or
intensive care units with moderate respiratory distress during the
period between August 2011 and November 2012 were recruited
on their date of birth. Ninety of them were excluded (Figure 1) All
infants less than 12 hours old who were diagnosed with moderate
RDS (clinical respiratory distress, pCO2<65mmHg, oxygen
requirement greater than 30%, radiological findings of poor lung
expansion) were considered for the study.
Respiratory distress was defined as sternal retraction,
intercostal and sub costal recession, grunting, tachypnea. Exclusion
criteria were major congenital malformations, neuromuscular
disease, severe birth asphyxia (Apgar score at 5 minutes of less
than 4, serum bicarbonate <12mmol/l in the first hour), sepsis,
pneumothorax, cleft palate and hydrops fetalis . The study
protocol was approved by our Ethics Institutional Review Board
and informed consent was obtained from the children’s parents
in every case.
We have routinely delivered nCPAP with a hybrid system:
binasal Hudson prongs combined with the Fisher & Paykel
pressure delivery device (Fisher & Paykel Healthcare Limited,
Auckland, New Zealand) [11,12]. This system was utilized in every
case assigned to nCPAP. As for the Infant Flow Driver (VF) group,
we used the Viasys SiPaP system (Viasys Healthcare, Yorba Linda,
CA, USA) with nasal prongs. Both devices were calibrated against
and independent oxygen analyzer to determine any differences in
After parental consent was obtained in every case, the infants
were prospectively and randomly assigned (by drawing a sealed,
numbered envelope) to either VF or nCPAP. This was done by the
inhalotherapy group, using sequentially numbered containers.
According to a preset protocol, continuous distending pressure
was initially set at 5cm H2O in both groups. Similarly, CDP was
increased if a fraction of inspired O2(FiO2)>0.6 was required
to keep saturated O2 in the range of 90-95%, depending on
Only in those who developed apnea, theophylline was started
with a loading dose of 5mg/kg given intravenously followed by
a daily maintenance dose of 1mg/kg given intravenously every
8h, as we didn’t have caffeine in México. Oxygen requirements,
respiratory rate, heart rate and saturated O2 by pulse oximetry
were monitored continuously. Blood gases were determined on
capillary blood every 6h during the first 24 hours of treatment and
every 8h thereafter or at the discretion of the health care team.
Non-invasive blood pressure was obtained by oscillometry
every 8h during the first 24h of treatment and every 12h
thereafter. All infants underwent a brain ultrasound at enrollment
and at least three times subsequently; the prongs were fixed with
the help of a technician in order to get the cerebral ultrasound.IVH
was classified as described by Papile et al
Any adverse clinical events (abdominal distension, pulmonary
air leaks, nasal injury and damage to septal mucosa) were also
prospectively recorded. Demographic data, antenatal steroids,
surfactant use, vital signs, arterial gases and ventilator parameters
were recorded, as well as CPAP failure and total CPAP and oxygen
time. We also documented associated morbidities such as NEC,
PDA and BPD.
Success was defined as the ability to remain CPAP-free
(medically stable with pCO2<60mmHg, saturated O2>95%
without supplementary O2 requirement). Failure to wean was
defined by an increase in pCO2 above 65mmHg and/or pH<7.25
on two consecutive occasions, O2 requirement >60% at CDP of
6cm H2O to keep saturated O2>90% for more than 4 consecutive
hours, more than 2apneic episodes/hour requiring stimulation or
bag ventilation. Adverse events such as air leaks and hyperemia of
the nasal mucosa are defined in our Neonatal Guidelines. In such
cases, further management was at the discretion of the health care
The sample size was estimated from a previous study that
reported 20% failure with the conventional nCPAP system in our
Institution  using a power of 85% and a significance level of
0.05. We used the difference in proportions formula  with
p=90, p2=70, Δ=20, β=0.20and α=0.05, which yielded a sample
size of 50 patients per group. Differences between the two groups
were assessed using the chi-square test or Fisher’s exact test
for categorical variables, whereas continuous variables were
analyzed using Student’s t-test or the Mann-Whitney test. Data
were processed using the SPSS software package (Chicago, Illinois,
A total of 101 infants were enrolled in our study and randomly
assigned to one of the two treatment groups (Figure 1). The
baseline characteristics of infants are summarized in Table 1 & 2.
There were no significant differences in relevant clinical data at
the time of enrollment. Gestational age, birth weight and gender at
the beginning of the study, were similar among treatment groups.
Physiological variables including respiratory rate and FiO2
requirement at entry didn’t show significant differences. History
of antenatal steroids was present in almost half of the infants in
both groups. Exogenous surfactant administration was similar
between both groups as well as xanthine management for apneas.
As for relevant morbidities during hospitalization, there were also
no significant differences between the two treatment groups.
In this study we found a similar proportion of treatment failure
between both modalities of CPAP. The duration of treatment in
hours differed slightly and it was longer in the nCPAP group but
without reaching statistical significance. With regard to adverse
events, we found a higher proportion of nasal mucosa hyperemia
in the VF group, although the difference was not statistically
significant. We found the same number of pulmonary air leaks in
The main purpose of this study was to compare the safety
and efficacy of nCPAP vs. VF in the management of moderate RDS
in our Institution. In a randomized controlled trial done in Rio J
et al. . evaluated efficacy and safety of nCPAP using devices
with variable flow or bubble continuous positive airway pressure.
CPAP failure, presence of air leaks, total CPAP and oxygen time
in neonates with moderate respiratory distress and birth weight
>1500g was evaluated and found no differences between the two
groups. They concluded, as we did that nCPAP showed the same
benefits as the use of variable flow NCPAP . In a previous RCT
by Mazzella et al.  comparing the effectiveness of the infant flow
driver (IFD) against single prong nasal continuous positive airway
pressure (nCPAP), IFD-treated patients were shown to have lower
oxygen requirement, a decreased respiratory rate and higher rate
of successful weaning and shorter duration of treatment, although
the difference in these two last outcomes failed to reach statistical
In our study we found a slightly longer duration of treatment
in the nCPAP group but without statistical significance as well as
a similar proportion of treatment failure for both modalities. In
2010 Lista et al.  compared synchronized bi-level CPAP and
standard nCPAP in infants 28-34 weeks gestation with respiratory
distress. They found no differences in short-term markers of
inflammation between treatments. They found that infants
treated with bi-level CPAP had a significantly shorter duration
of respiratory support and supplemental oxygen than the group
randomized to standard CPAP . We were not able to find such
differences. For the past 15 years, the medical staff, residents and
nurses have acquired expertise and are used to handle nCPAP, and this could be an important issue associated with these outcomes,
since the IFD system is relatively new compared with nasal bubble
In 2012 O’ Brien et al.  performed a randomized controlled
trial of bi-level CPAP versus standard nasal CPAP to facilitate
sustained extubation in babies <1250g and found that the use of
bi-level CPAP was as effective as standard CPAP . As for BPD
incidence in this study, it is reported high in both groups. México
City is located at 2420 m above sea level and for many years it has
been noted that oxygen dependency is greater at higher altitudes,
and this leads to an increase in the diagnosis of BPD. Despite this,
the standard for the diagnosis of BPD is the requirement of and
oxygen concentration over 21% as it is for patients at sea level. At
present, there are no references for oxygen dependency at higher
altitudes according to barometric pressures for the purpose of
BPD classification. This could be the reason for the variation in
oxygen dependency and the apparent increase in BPD incidence
in México City .
The authors thank Dr Carlos Alfonso Fajardo (Director of
the SIBEN Neonatal Network) for the revision of this article and
useful input and the nursing staff of the InstitutoNacional de
Perinatología for their invaluable help in this research.
Dra Romero-Maldonado and DraEchániz-Avilés contributed
equally in the design and analysis of the results. Hernández-Ruiz
and Delgado Franco participated in the recruitment and follow-up
of the patients. Pérez-Valdez as well as López-Pérez was invaluable
in assisting in the patient’s management.