Original Paper
Neonatology 2015;108:277–282
DOI: 10.1159/000437204
Impact of Volume Guarantee on High-Frequency
Oscillatory Ventilation in Preterm Infants:
A Randomized Crossover Clinical Trial
Burcin Iscan Nuray Duman Funda Tuzun Abdullah Kumral Hasan Ozkan
Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
Key Words
High-frequency oscillatory ventilation · Hypocarbia ·
Optimal lung volume strategy · Randomized controlled
trial · Premature infant · Ventilator-induced lung injury ·
Volume guarantee · Volume-targeting ventilation
Abstract
Background: High-frequency oscillatory ventilation (HFOV)
with volume guarantee (VG) is a new ventilation mode that
allows the clinician to set a mean tidal volume to be deliv-
ered. Objective: This study aimed to investigate whether
HFOV with a VG option may result in constant tidal volume
delivery and less fluctuant CO2 levels compared to HFOV
alone in premature infants with respiratory distress syn-
drome (RDS). Methods: Inborn infants at less than 32 weeks
of gestation with RDS requiring invasive mechanical ventila-
tion were eligible. Patients were randomized to receive
HFOV + VG or HFOV alone as the initial ventilator mode and
then crossed over to the other mode. HFOV was performed
with ‘optimal lung volume strategy’ during both of the peri-
ods. Results: Twenty infants were evaluated. The mean high-
frequency tidal volume (VThf) and CO2 diffusion coefficient
(DCO2) were significantly higher in the HFOV + VG mode
than HFOV alone. HFOV + VG maintains VThf within the tar-
get range more consistently than HFOV. The incidences of
hypocarbia and hypercarbia were lower in HFOV with VG
© 2015 S. Karger AG, Basel
1661–7800/15/1084–0277$39.50/0
E-Mail karger@karger.com
www.karger.com/neo
Received: April 8, 2015
Accepted after revision: June 24, 2015
Published online: September 1, 2015
than HFOV alone. Conclusion: This is the first prospective,
randomized, short-term crossover clinical study that com-
pared HFOV with and without VG in infants with acute RDS.
Because of the lower VThf fluctuation and lower incidences
of out-of-target PCO2 levels, HFOV combined with VG seems
to be feasible for preterm infants. However, the results
should be interpreted with caution due to the small sample
size and short-term crossover design of the study.
© 2015 S. Karger AG, Basel
Menos DBP pero mas fuga aerea y
mas daño neuro
Introduction
High-frequency oscillatory ventilation (HFOV) has
been widely used for the treatment of infants with respira-
tory distress syndrome (RDS) [1]. Potential advantages of
HFOV over conventional mechanical ventilation include
the use of small tidal volumes and the safer use of higher
mean airway pressure than is generally used during con-
ventional mechanical ventilation [2]. According to the re-
sults of the latest Cochrane review [3], the use of elective
HFOV compared with conventional mechanical ventila-
tion results in a minor reduction in the risk of chronic lung
disease; however, the evidence is weakened by the incon-
sistency of this effect across trials. In addition, the benefit
could be counteracted by an increased risk of acute air leak
and poor short-term neurological outcomes.
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania
Prof. Dr. Hasan Ozkan
Division of Neonatology, Department of Pediatrics
Faculty of Medicine, Dokuz Eylül University
Downloaded by:
TR–35340 Izmir (Turkey)
E-Mail hozkandeu @ gmail.com
 Vafo +vg vtidal mas constante y
CO2 también
Although several mechanisms of gas exchange have
been described, high-frequency tidal volume (VThf) is
very important for CO2 elimination during HFOV. VThf
is mostly generated by fluctuations of the pressure (ΔPhf)
around the mean airway pressure (Paw) and the frequency
(ƒ) [4]. The amount of VThf can also be related to other
factors such as endotracheal tube size and lung compli-
ance [5]. All of these factors can cause large variations of
tidal volume and CO2 removal, which may reduce the ef-
fectiveness of high-frequency oscillation [6].
A new concept of volume-targeted ventilation during
HFOV has been introduced in some new-generation neo-
natal HFOV devices. Volume-targeted ventilation is
known to improve neonatal prognosis in preterm infants
when added to conventional ventilation [7, 8]. However,
volume-targeted ventilation combined with high-fre-
quency ventilation has not been adequately evaluated.
We hypothesized that when compared to HFOV alone,
HFOV with volume guarantee (VG) may result in con-
stant tidal volume delivery and less fluctuant CO2 levels
in premature infants with RDS.
24-32 sdg. Incubación primeras 6 horas. De
inicio Vafo o Vafo mas vg
Materials and Methods
Study Design, Patients and Interventions
The randomized, crossover, prospective trial was conducted at
the Neonatal Intensive Care Unit (NICU) at Dokuz Eylül Univer-
sity Hospital in Izmir, Turkey, from August 2013 to September
2014. Inborn premature infants at 24–32 weeks’ gestation who re-
quired endotracheal intubation in the delivery room or in the NICU
within the first 6 h of life owing to severe RDS were considered eli-
gible for the study. Patients receiving neuromuscular paralysis or
narcotic analgesics and those with >20% endotracheal tube leak and
congenital anomalies affecting the cardiac, respiratory or central
nervous system were excluded. Although we usually allow endotra-
cheal tube leaks up to 40% in clinical practice, we wanted to negate
the effect of leakage in this trial. All enrolled infants received surfac-
tant treatment (200 mg/kg, Curosurf®; Chiesi Pharmaceuticals,
Parma, Italy) in the delivery room or in the NICU and ventilated
initially using the Assist Control (A/C) with VG mode (VN500;
Draeger, Lübeck, Germany) approximately for a 1-hour stabiliza-
tion period. Infants were randomly assigned to receive either HFOV
or HFOV with VG as the initial ventilation mode using a block ran-
domization. Patients were treated for another 2 h with the first
mode of ventilation. At the end of the initial 2 h, patients were then
crossed over to the other mode of ventilation for 2 h. There was a
minimum 15-min ‘washout’ period between the changes in the ven-
tilator modes using the A/C with VG mode. In this study, we used
early HFOV instead of rescue therapy as we aimed to evaluate the
short-term effects of HFOV before lung mechanics and PCO2 levels
are affected by conventional mechanical ventilation.
Parents gave informed consent and the study protocol was ap-
proved by the institute’s committee on human research (Dokuz
Eylül University Faculty of Medicine, Committee on Human Re-
search). 1 hr Vafo mas vg
Luego 2 Hrs Vafo al azar
Luego 2 Hrs con el otro Vafo
278 Neonatology 2015;108:277–282
DOI: 10.1159/000437204
Ventilators
HFOV was delivered with a Draeger VN500 ventilator. The
VN500 ventilator uses a venturi system to generate oscillatory
pressure amplitudes and resultant tidal volumes during HFOV.
The VG mode is volume-targeted ventilation. The clinical team
selects a target VT and an amplitude pressure limit during the
HFOV combined with VG ventilation. The microprocessor
compares the VT of the previous breath, using exhaled VT, and
adjusts the working pressure up or down to try to achieve the
set VT.
Ventilation Strategies No mencionan Paw
The ventilation strategy was performed similarly with an op-
timal volume strategy in both periods. Opening pressure, closing
pressure and optimal pressure were determined using the lung
recruitment maneuver as previously described [9]. The time
spent during mean arterial blood pressure adjustments was not
included in the study period. After the lung recruitment maneu-
ver, lung volume was controlled by chest radiography and the
right diaphragm was kept at the level of the 9th rib. A constant
frequency of 10 Hz and oscillatory inspiratory/expiratory ratio
of 1:1 were used in all infants during both high-frequency venti-
lation periods. The amplitude set at equal to the Paw value at the
beginning was increased until visible chest wall movement was
observed and VThf equaled 2 ml/kg in the high-frequency oscil-
lation without VG period. If the PCO2 value was outside the tar-
get range, the amplitude was adjusted up or down in increments
of 10–20% as necessary in the HFOV alone period. On the basis
of our clinical experience, in the HFOV + VG mode, the VThf was
set at 2 ml/kg initially. The amplitude limit was set at 15–20%
above the average amplitude needed to achieve the target VThf.
Subsequently, if the PCO2 value was outside the target range, the
set VThf was adjusted by the clinical team in increments of 0.5
ml/kg as necessary. In the present study, target ranges for PCO2
and pH values during the first 24 h of life were accepted as 5–7
and 7.25–7.40 kPa, respectively [10]. Arterialized capillary blood
gases were measured on admission, at the 20th min after ran-
domization and then at 30- to 40-min intervals or more often as
needed using a blood gas analyzer (ABLTM 700; Radiometer, Co-
penhagen, Denmark). Fraction of inspired oxygen (FiO2) was
given as needed to achieve an SpO2 between 90 and 95% by pulse
oximetry.
Data Acquisition and Analysis
A hot-wire anemometer placed on the airway opening contin-
uously measured the flow and tidal volume during HFOV. VThf,
Paw, pressure swing around the mean Paw (∆Phf) and the CO2 dif-
fusion coefficient (DCO2) were calculated as VT2 × fR (ml2/s) and
recorded at 5-min intervals using proprietary software (VentView
2.n software; Draeger). The infants were switched to conventional
ventilation at the end of each period and both consecutive breaths
dynamic compliance (CDyn) and airway resistance (R) were mea-
sured during conventional ventilation. The data were then con-
verted into a spreadsheet (Microsoft Excel; Microsoft Corp., Red-
mond, Wash., USA) for analysis. These data were averaged over
2-hour periods and the mean values were compared between the
groups. Infants were also monitored using pulse oximetry (Mashi-
mo Radical 7; Mashimo Corp., Irvine, Calif., USA) and blood pres-
sure measurements were recorded at 15-min intervals (Infinity
Kappa; Draeger).
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania
Iscan/Duman/Tuzun/Kumral/Ozkan
Downloaded by:
 Statistics Table 1. Patient characteristics
The main outcome variables were the percentages of time that
VThf and PCO2 were outside the target range. Power analysis, Subject Gender GA, Weight, 5′ Apgar Surfactant, Age at intu-
based on an anticipated reduction of the proportion of PCO2 out- No. weeks g score doses bation, h
side the target range from 40 to 20%, yielded a need for 20 obser-
vations per group (α: 0.05; power: 80%). The normality of data was 1 female 26 927 7 1 0
determined by a one-sample Kolmogorov-Smirnov test. The χ2 2 male 26 876 4 1 0
test for dependent groups (McNemar’s test) was used to analyze 3 male 28 921 8 1 2
categorical variables, including the proportion of VThf and PCO2 4 male 29 704 6 1 0
outside the target range. The paired sample t test was used to com- 5 female 28 1,060 7 1 0
pare continuous variables. Statistical analysis was performed using 6 female 27 1,080 7 1 0
the SPSS 15.0 software program (IBM SPSS Statistics, Chicago, Ill., 7 male 32 1,376 7 1 4
USA). Statistical significance was set at p < 0.05. 8 female 32 1,960 9 1 2
20 bebés 9 male 31 1,150 9 1 1
10 male 28 1,240 7 2 0
11 male 32 1,364 7 1 0
Results 12 female 24 737 6 1 0
13 male 24 740 7 1 0
A total of 116 preterm infants less than 32 weeks’ ges- 14 male 27 821 5 1 2
tation were admitted to the NICU during the study pe- 15 female 27 580 5 1 0
16 female 32 2,055 6 1 1
riod. Twenty-four infants were considered eligible for the 17 male 27 802 6 1 1
study; however, 4 infants were excluded owing to the ex- 18 male 27 1,150 7 2 0
clusion criteria (1 with cardiac anomaly and 3 with endo- 19 male 28 1,244 6 1 0
tracheal tube leakage). The study population consisted of 20 male 28 853 8 2 0
infants who were 28 ± 2.4 weeks’ gestation and 1,080 ±
GA = Gestational age.
390 g. Thirteen infants were intubated and administered
surfactant in the delivery room, whereas the remaining 7
infants were intubated and administered surfactant in the
Table 2. Data on the prestudy period ventilation characteristics
NICU within the median 2nd hour of life. The median age and blood gases analysis in the A/C + VG mode
at the entry to the study was the 1st hour of life (range:
1–5). The demographic and clinical characteristics of the Measurements Mean ± SD Range
infants are summarized in table 1. Data on the prestudy
period ventilation characteristics and blood gases analysis PIP, cm H2O 15.1 ± 4.6 12 – 22
results in A/C + VG mode are summarized in table 2. Paw, cm H2O 8.6 ± 1.4 6.7 – 12
FiO2, % 26.9 ± 11,6 21 – 85
Paw, amplitude, VThf, DCO2 and FiO2 were obtained VT, ml/kg 4.3 ± 1.8 3.5 – 5.2
from infants during each trial period. CDyn and R values PEEP, cm H2O 5.9 ± 0.3 4.8 – 6.7
were recorded during the course of conventional ventila- CDyn, ml/cm H2O/kg 0.84 ± 0.4 0.33 – 1.70
tion, during washout periods and upon the completion of R, cm H2O/l/s 102 ± 34 72 – 137
the trial periods. There were no differences between venti- pH 7.26 ± 0.08 7.09 – 7.40
PCO2, mm Hg 54.07 ± 13.2 31.9 – 87
lation modes in terms of mean Paw, amplitude, FiO2, CDyn HCO3, mEq/l 20.57 ± 2.05 16.9 – 24.7
or R during each trial period (table  3). However, mean
VThf and DCO2 decreased significantly during the HFOV PIP = Peak inspiratory pressure; PEEP = positive end-expira-
period (p = 0.019 and p = 0.038, respectively; fig. 1). tory pressure.
When compared to HFOV alone, the proportion of
PCO2 values outside the target range was significantly
lower during the HFOV + VG period (table 4). The pro- 0.03). However, the proportion of VThf values above the
portion of VThf values within the target range (1.5–2.5 target range (>2.5 ml/kg) was not significantly different
ml/kg) was significantly higher during the HFOV + VG between the two periods (fig. 2).
period, compared to the HFOV alone period (80 and The median number of ventilator adjustments per pa-
35%, respectively; p = 0.004). The proportion of VThf val- tient was 2 (range: 1–4) in the HFOV mode and 1 (range:
ues below the target range (<1.5 ml/kg) was also signifi- 1–2) in the HFOV + VG mode (p = 0.502). The median
cantly lower during the HFOV + VG period compared to number of blood gas assessments per patient was 2 (range:
the HFOV alone period (15 and 45%, respectively; p = 2–4) in the HFOV mode, and 2 (range: 2–3) in the HFOV
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania

HFOV with VG Neonatology 2015;108:277–282 279

DOI: 10.1159/000437204
Downloaded by:
 2.50 100 25

80

Amplitude (cm H2O)

2.00 20

DCO2 (ml2/s)
VThf (ml/kg)

60
1.50 15
40
1.00 10
20

0.50 0 5
a HFOV HFOV + VG b HFOV HFOV + VG c HFOV HFOV + VG

Fig. 1. Evaluation of VThf, DCO2 and amplitude levels in the
HFOV and HFOV + VG groups. a Evaluation of VThf values in
the HFOV and HFOV + VG groups. There was a significant dif-
ference between the two groups in terms of VThf values (p = 0.019).
b Evaluation of gas transport coefficient (DCO2) in the HFOV and
HFOV + VG groups. Mean DCO2 measurements were significant-
ly different between the HFOV and HFOV + VG groups (p =
0.038). c Evaluation of the amplitude levels in the HFOV and
HFOV + VG groups. There was not a statistically significant dif-
ference between the two groups regarding mean amplitude mea-
surements (p = 0.218). The lower and upper margins of each box
correspond to quartiles (i.e. percentiles 25 and 75), the line in the
middle of the box corresponds to the median, the whiskers corre-
spond to percentiles 10 and 90, and stars correspond to extremes.

Table 3. Ventilation characteristics and blood gas analysis results during the trial periods

Measurements HFOV HFOV+VG Paired t test Difference score

(n = 20) (n = 20) p values mean±SD 95% CI
mean ± SD mean ± SD
lower upper

Amplitude, cm H2O 14.04 ± 4.72 15.47 ± 4.55 0.218 –1.43 ± 5 –3.77 0.91
Paw, cm H2O 10.05 ± 1.85 9.99 ± 1.86 0.195 0.06 ± 0.22 –0.03 0.17
FiO2, % 23.45 ± 3.72 22.35 ± 3.15 0.217 1.1 ± 3.85 –0.7 2.9
VThf, ml/kg 1.59 ± 0.45 1.82 ± 0.18 0.019* –0.22 ± 0.39 –0.41 –0.04
DCO2, ml2/s 35.6 ± 19.1 40.5 ± 13.4 0.038* –4.88±.2 –13.4 –3.6
CDyn, ml/cm H2O/kg 1.01 ± 0.87 0.86 ± 0.63 0.437 0.15 ± 0.88 –0.25 0.56
R, cm H2O/l/s 96.8 ± 30 87.6 ± 33.6 0.075 9.2 ± 21.8 –1 19.4
pH 7.29 ± 0.75 7.33 ± 0.54 0.014* – 0.4 ± 0.3 –0.04 –0.01
PCO2, mm Hg 49.1 ± 10.7 43.9 ± 7.5 0.013* 5.2 ± 2.4 3.5 5.1
HCO3, mEq/l 21.1 ± 1.6 21.8 ± 1.6 0.07 –0.69 ± 2 –1.2 0.07

* p < 0.05.

La oxigenación es igual

+ VG mode (p = 0.930). All of the cases achieved target
blood gas by the end of the HFOV + VG period, whereas
4 infants did not achieve it by the end of the HFOV alone
period (p = 0.034).
Overall, 51 (63%) normocapnic measurements, 11
(13%) hypocapnic measurements and 19 (24%) hypercap-
nic measurements were recorded during all the periods.
The median VThf levels at the time of the normocapnic,
hypocapnic and hypercapnic measurements were 1.74 ±
0.41 (95% CI: 1.64–1.85), 1.97 ± 0.16 (95% CI: 1.76–2.17)
and 1.59 ± 0.38 (95% CI: 1.37–1.82), respectively.
There was no difference between ventilation modes in
terms of mean heart rate, SpO2, perfusion index, Pleth
variability index and mean arterial blood pressure during
each trial period.
Discussion
This is the first prospective, randomized, crossover clin-
ical trial comparing HFOV with and without VG in infants
with acute RDS. The present study has demonstrated that
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania

280 Neonatology 2015;108:277–282 Iscan/Duman/Tuzun/Kumral/Ozkan

DOI: 10.1159/000437204
Downloaded by:

% High VThf
100 Target VThf
15% Low VThf
20%
80
60 35%
80%
40
45%
20
5%
0
HFOV HFOV + VG
Fig. 2. Incidence of low, normal and high VT during each study
period.
Volumen tidal constante pese a
cambios de la cmplianza
HFOV with VG reduces the incidence of PCO2 exceeding
the target range and maintains VThf within the target range
more consistently than HFOV alone.
To our knowledge, there is only one published animal
study assessing the effects of an HFOV + VG strategy on
CO2 levels in an experimental model of RDS. The results
indicated that changes in the VThf settings caused signif-
icant alterations in PCO2 during HFOV + VG. In addi-
Puercostion, after changing the lung condition by depletion of
surfactant, PCO2 remained unchanged, as the VThf set-
ting was maintained constant by modifications in the am-
plitude determined by the ventilator [11]. Similarly, the
present study demonstrated more uniform tidal volume
delivery during VG ventilation even under conditions of
rapidly changing lung compliance in the first hours of life.
The most important consideration is that the optimal
initial value of set VThf is not yet clearly known. We ini-
tially used a target VThf of 2 ml/kg as the expected dead
space was thought to be approximately 2.2 ml/kg in
healthy awake neonates [12]. To date, few studies have
evaluated the optimal VThf target in neonates during
HFOV. Zimova-Herknerova and Plavka [6] showed that
the median delivered normocapnic tidal volume during
HFOV was 1.67 ml/kg, and the median hypocapnic and
hypercapnic tidal volumes were 1.94 ml/kg and 1.54 ml/
kg, respectively, in a heterogeneous group of newborns
ventilated by HFOV at any time during their hospital
stay. Our study demonstrated that the median delivered
normocapnic tidal volume during HFOV was 1.74 ml/kg,
HFOV with VG
Table 4. The incidence of hypercarbia and hypocarbia in the study
periods
PCO2, HFOV HFOV+VG pb
mm Hg (kPa) (n = 41)a (n = 40)a
37.5 – 52.5 (5 – 7) 21 30 0.04**
≤37.5 (≤5) 7 4 0.01**
≥52.5 (≥7) 13 6 0.014**
a
Number of blood samples in each period. b χ2 test for depen-
dent groups (McNemar’s test). ** p < 0.05.
median hypocapnic tidal volume was 1.97 ml/kg and me-
dian hypercapnic tidal volume was 1.54 ml/kg in preterm
infants during the initial phase of RDS. Further studies
are needed to investigate whether these values change
with gestational or postnatal age and underlying disease.
An HFOV + VG strategy allows for the independent
adjustment of VThf and frequency. We used a constant
frequency to reduce the determinants of VThf. Mukerji et
al. [13] compared the DCO2 and VT values against the
frequencies of 5–15 Hz both with and without a constant
VT in an artificial lung model. They suggested that if
VThf can be held constant and delivered reliably, the high-
est frequency should be used to maximize ventilation ef-
ficacy while minimizing barotrauma. It is interesting to
note that this challenges the current practice of using a
starting frequency of 10 Hz in HFV. As they suggested,
the clinical benefit of utilizing such a strategy is unknown
and requires further clinical investigation.
There were three main limitations of this study: cross-
over design, small sample size and lack of follow-up. The
main strengths were the randomized prospective design
and objective results based on continuous and standard-
ized measurements.
In summary, our results suggest that when compared
to HFOV alone, an HFOV + VG strategy provides better
ventilation and can achieve optimal gas exchange. Be-
cause of the lower VThf variability and lower incidences
of out-of-target PCO2 levels, HFOV + VG seems to be
feasible for preterm infants. The results of this study need
to be interpreted cautiously. It should be noted that this
was a selected population of preterm infants with very
low leak who were studied over a short period of time;
therefore, the results cannot be extrapolated to all infants
on HFOV. Further randomized controlled studies with
larger sample sizes are required to determine if HFOV +
VG offers short- and long-term advantages over HFOV
alone in preterm infants with RDS.
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania
Neonatology 2015;108:277–282 281
DOI: 10.1159/000437204
Downloaded by:
 Disclosure Statement
received to support this study.
References
1 Van Kaam AH, Rimensberger PC, Borensz-
tajn D, De Jaegere AP; Neovent Study Group:
Ventilation practices in the neonatal intensive
care unit: a cross-sectional study. J Pediatr
2010;157:767–771.
2 Rehan VK, Fong J, Lee R, Sakurai R, Wang
ZM, Dahl MJ, Lane RH, Albertine KH, Tor-
day JS: Mechanism of reduced lung injury by
high-frequency nasal ventilation in a preterm
lamb model of neonatal chronic lung disease.
Pediatr Res 2011;70:462–466.
3 Cools F, Offringa M, Askie LM: Elective high
frequency oscillatory ventilation versus con-
ventional ventilation for acute pulmonary
dysfunction in preterm infants. Cochrane Da-
tabase Syst Rev 2015;3:CD000104.
4 Slutsky AS, Drazen JM: Ventilation with
small tidal volumes. N Engl J Med 2002; 347:
630–631.
5 Singh R, Courtney SE, Weisner MD, Habib
RH: Respiratory mechanics during high-
frequency oscillatory ventilation: a physical
282 Neonatology 2015;108:277–282
DOI: 10.1159/000437204
All of the authors stated that there is no conflict of interest. No financial assistance was
model and preterm infant study. J Appl Physi-
ol (1985) 2012;112:1105–1113.
6 Zimova-Herknerova M, Plavka R: Expired
tidal volumes measured by hot-wire ane-
mometer during high-frequency oscillation
in preterm infants. Pediatr Pulmonol 2006;41:
428–433.
7 Duman N, Tuzun F, Sutcuoglu S, Yesilırmak
CD, Kumral A, Ozkan H: Impact of volume
guarantee on synchronized ventilation in pre-
term infants: a randomized controlled trial.
Intensive Care Med 2012;38:1358–1364.
8 Peng W, Zhu H, Shi H, Liu E: Volume-tar-
geted ventilation is more suitable than pres-
sure-limited ventilation for preterm infants:
a systematic review and meta-analysis. Arch
Dis Child Fetal Neonatal Ed 2014; 99: 158–
165.
9 Sun H, Cheng R, Kang W, Xiong H, Zhou C,
Zhang Y, Wang X, Zhu C: High-frequency os-
cillatory ventilation versus synchronized in-
termittent mandatory ventilation plus pres-
sure support in preterm infants with severe
respiratory distress syndrome. Respir Care
2014;59:159–169.
10 Guidelines for Good Practice in the Manage-
ment of Neonatal Respiratory Distress Syn-
drome. Report of the Second Working Group
of the British Association of Perinatal Medi-
cine. London, British Association of Perinatal
Medicine, 1999.
11 Sánchez Luna M, Santos Gonzáles M, Tendil-
lo Cortijo F: High-frequency oscillatory ven-
tilation combined with volume guarantee in a
neonatal animal model of respiratory distress
syndrome. Crit Care Res Pract 2013; 2013:
593915.
12 Numa AH, Newth CJ: Anatomic dead space
in infants and children. J Appl Physiol 1996;
80:1485–1489.
13 Mukerji A, Belik J, Sanchez-Luna M: Bringing
back the old: time to reevaluate the high-fre-
quency ventilation strategy. J Perinatol 2014;
34:464–467.
198.143.38.1 - 9/5/2015 1:36:30 AM
University of Pennsylvania
Iscan/Duman/Tuzun/Kumral/Ozkan
Downloaded by: