Noninvasive respiratory support of juvenile rabbits by high-amplitude bubble continuous positive airway pressure.
ABSTRACT Bubble continuous positive airway pressure (B-CPAP) applies small-amplitude, high-frequency oscillations in airway pressure (DeltaPaw) that may improve gas exchange in infants with respiratory disease. We developed a device, high-amplitude B-CPAP (HAB-CPAP), which provides greater DeltaPaw than B-CPAP provides. We studied the effects of different operational parameters on DeltaPaw and volumes of gas delivered to a mechanical infant lung model. In vivo studies tested the hypothesis that HAB-CPAP provides noninvasive respiratory support greater than that provided by B-CPAP. Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP. The animals were then supported at the same mean airway pressure, bias flow, and fraction of inspired oxygen (FiO2) required for stabilization, whereas the bubbler angle was varied in a randomized crossover design at exit angles, relative to vertical, of 0 (HAB-CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90), and 135 degrees (HAB-CPAP135). Arterial blood gases and pressure-rate product (PRP) were measured after 15 min at each bubbler angle. Pao2 levels were higher (p<0.007) with HAB-CPAP135 than with conventional B-CPAP. PaCO2 levels did not differ (p=0.073) among the three bubbler configurations. PRP with HAB-CPAP135 were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p=0.001). These results indicate that HAB-CPAP135 provides greater respiratory support than conventional B-CPAP does.
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ABSTRACT: Non-invasive high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed to combine the advantages of oscillatory pressure waveform and non-invasive interface. We studied the effect of oscillation amplitude and inspiratory time on the pressure transmission and tidal volume delivery through different nasal prongs. In vitro mechanical study on a previously described bench model of nHFOV. The model was built connecting SM3100A tubings to a neonatal lung model, via two differently sized binasal prongs. A circuit with no nasal prongs was used as control. Tidal volume (T(v) ), oscillatory pressure ratio (ΔP(dist) /ΔP(prox) ), and ventilation (DCO(2) ) were measured across a range of amplitudes and inspiratory times (I(T) ). Measurements were performed with a low-dead space hot wire anemometer coupled with a pressure transducer. Using both nasal prongs, T(v) , ΔP(dist) /ΔP(prox) , and DCO(2) were 83%, 40%, and 71%, respectively, of those provided with the control circuit. No differences were noticed between small and large prongs. T(v) and ΔP(prox) were linked by a quadratic relationship. T(v) plateaus for amplitude values >65 cmH(2) O. ΔP(dist) /ΔP(prox) shows same tendency. Same results were obtained with both types of prongs and with increasing I(T) . On the whole, mean T(v) was higher with I(T) at 50% than at 33% (2.4 ml vs. 1.4 ml; P < 0.001). Changing oscillation amplitude and I(T) has a significant effect on ventilation. Varying these two parameters provides a theoretical T(v) within the ideal values for HFOV also using the smallest nasal prongs. Pediatr Pulmonol. 2012. 47:1012-1018. © 2012 Wiley Periodicals, Inc.Pediatric Pulmonology 02/2012; 47(10):1012-8. · 2.38 Impact Factor
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ABSTRACT: Background:Short-term high-frequency nasal ventilation (HFNV) of preterm neonates provides acceptable gas exchange compared to endotracheal intubation and intermittent mandatory ventilation (IMV). Whether long-term HFNV will provide acceptable gas exchange is unknown. We hypothesized that HFNV for up to 21d would lead to acceptable gas exchange at lower inspired oxygen (O2) levels and airway pressures compared to intubation and IMV.Methods:Preterm lambs were exposed to antenatal steroids, and treated with perinatal surfactant and postnatal caffeine. Lambs were intubated and resuscitated by IMV. At ~3h of age, half of the lambs were switched to non-invasive HFNV. Support was for 3d or 21d. By design, PaO2 and PaCO2 were not different between groups.Results:At 3d (n=5) and 21d (n=4) of HFNV, fractional inspired O2 (FiO2), peak inspiratory pressure, mean airway, intra-tracheal, and positive end-expiratory pressures, oxygenation index, and Alveolar-arterial gradient were significantly lower than matched periods of intubation and IMV. PaO2/FiO2 ratio was significantly higher at 3d and 21d of HFNV compared to matched intubation and IMV. HFNV led to better alveolarization at 3d and 21d.Conclusion:Long-term HFNV provides acceptable gas exchange at lower inspired O2 levels and respiratory pressures compared to intubation and IMV.Pediatric Research (2013); doi:10.1038/pr.2013.254.Pediatric Research 12/2013; · 2.67 Impact Factor
Article: The new bronchopulmonary dysplasia.[Show abstract] [Hide abstract]
ABSTRACT: Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new information about pathophysiology and treatment. The epidemiology of BPD continues to demonstrate that birth weight and gestational age are most predictive of BPD. Correlations of BPD with chorioamnionitis are clouded by the complexity of the fetal exposures to inflammation. Excessive oxygen use in preterm infants can increase the risk of BPD but low saturation targets may increase death. Numerous recent trials demonstrate that many preterm infants can be initially stabilized after delivery with continuous positive airway response (CPAP) and then be selectively treated with surfactant for respiratory distress syndrome. The growth of the lungs of the infant with BPD through childhood remains poorly characterized. Recent experiences in neonatology suggest that combining less invasive care strategies that avoid excessive oxygen and ventilation, decrease postnatal infections, and optimize nutrition may decrease the incidence and severity of BPD.Current opinion in pediatrics 12/2010; 23(2):167-72. · 2.01 Impact Factor
Noninvasive Respiratory Support of Juvenile Rabbits by
High-Amplitude Bubble Continuous Positive Airway Pressure
ROBERT M. DIBLASI, JAY C. ZIGNEGO, DENNIS M. TANG, JACK HILDEBRANDT, CHARLES V. SMITH,
THOMAS N. HANSEN, AND C. PETER RICHARDSON
Center for Developmental Therapeutics [R.M.D., J.C.Z., D.M.T., C.V.S., T.N.H., C.P.R.], Seattle Children’s Research Institute, Seattle, WA
98101; Department of Physiology and Biophysics [J.H.], University of Washington School of Medicine, Seattle, WA 98195
ABSTRACT: Bubble continuous positive airway pressure (B-
CPAP) applies small-amplitude, high-frequency oscillations in air-
way pressure (?Paw) that may improve gas exchange in infants with
respiratory disease. We developed a device, high-amplitude B-CPAP
(HAB-CPAP), which provides greater ?Pawthan B-CPAP provides.
We studied the effects of different operational parameters on ?Paw
and volumes of gas delivered to a mechanical infant lung model. In
vivo studies tested the hypothesis that HAB-CPAP provides nonin-
vasive respiratory support greater than that provided by B-CPAP.
Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP.
The animals were then supported at the same mean airway pressure,
bias flow, and fraction of inspired oxygen (FiO2) required for stabi-
lization, whereas the bubbler angle was varied in a randomized
crossover design at exit angles, relative to vertical, of 0 (HAB-
CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90),
and 135° (HAB-CPAP135). Arterial blood gases and pressure-rate
product (PRP) were measured after 15 min at each bubbler angle.
PaO2levels were higher (p ? 0.007) with HAB-CPAP135 than with
conventional B-CPAP. PaCO2levels did not differ (p ? 0.073)
among the three bubbler configurations. PRP with HAB-CPAP135
were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p ?
0.001). These results indicate that HAB-CPAP135 provides greater
respiratory support than conventional B-CPAP does. (Pediatr Res
67: 624–629, 2010)
that is used frequently as a primary strategy for supporting
spontaneously breathing preterm infants at risk of developing
respiratory distress syndrome. Compared with intubation and
mechanical ventilation, the use of B-CPAP has been associ-
ated with lower indicators of acute lung injury (1) and bron-
chopulmonary dysplasia (2).
Recent studies suggest that the bubbling of gas exiting the
B-nCPAP circuit at the water seal creates oscillations in
airway pressure (?Paw), having broadband high frequencies
ubble-nasal continuous positive airway pressure (B-
nCPAP) is a form of noninvasive respiratory support
(3), which may promote airway patency and enhance lung
volume and gas exchange in preterm lambs (4). However, a
study of 261 consecutively born premature infants revealed
that 24% of infants born weighing ?1250 g and 50% of
infants weighing ?750 g failed B-nCPAP and required endo-
tracheal intubation and mechanical ventilation (5). In an effort
to diminish the potentially deleterious effects of invasive
mechanical ventilation (6), we designed a novel device, high-
amplitude B-CPAP (HAB-CPAP), which, through alterations
in angle of gas entry at the water seal, may enhance respiratory
efficiency and improve oxygenation when compared with
In this report, we describe a device that provides ?Paw
higher in amplitude than B-CPAP. Studies were conducted to
determine the effects of bubbler angle and bias flow on ?Paw
and the amplitude of oscillations in volume (?V) delivered to
a mechanical model of an infant lung. In addition, studies
were conducted in spontaneously breathing, lung lavaged,
adolescent rabbits to test the hypothesis that HAB-CPAP
would provide greater gas exchange and lower inspiratory
work of breathing (WOB), as estimated by pressure-rate prod-
uct (PRP, an index of WOB), than are provided by conven-
MATERIALS AND METHODS
HAB-CPAP device. The HAB-CPAP device consisted of a dual limb
patient/subject circuit. The inhalation limb provided bias flow gas from a
flowmeter through a 4.8-mm ID Tygon tubing to the test lung or animal, and
the exhalation limb conveyed exhaled and bias flow gases through a 8-mm ID
Tygon tubing connected distally to an elbow, a swivel, and a bubbler (online
supplement: http://links.lww.com/PDR/A58). The swivel allowed for adjust-
ments in bubbler angle from 0 to 180°. A bubbler angle of 0° represented the
tube pointing straight down and is equivalent to conventional B-CPAP. The
abbreviations HAB-CPAP0, HAB-CPAP90, and HAB-CPAP135 designate
the HAB-CPAP device at bubbler angles of 0, 90, and 135°, respectively,
although low angles do not provide high-amplitude ?Paw. CPAP levels were
adjusted by the depth of immersion of the bubbler in the water column, and
they were defined as mean airway pressure (MAP) monitored proximal to the
Received September 28, 2009; accepted March 1, 2010.
C9S-9, 1900 Ninth Avenue, Seattle, WA 98101; e-mail: email@example.com
This research was funded by the Seattle Children’s Research Institute.
Seattle Children’s Research Institute (SCRI) has submitted a patent application to the
World Intellectual Property Organization (PCT/US2009/039957) concerning the HAB-
CPAP device described in this article. The application is in review and has not yet been
approved. However, authors R.M.D., J.C.Z., C.V.S., T.N.H., and C.P.R., who are listed
as inventors on the application, could benefit from the invention.
Supplemental digital content is available for this article. Direct URL citations appear
in the printed text and are provided in the HTML and PDF versions of this article on the
journal’s Web site (www.pedresearch.org).
Abbreviations: ?Paw, oscillations in airway pressure; ?V, oscillations in
volume; ABG, arterial blood gas analysis(es); B-CPAP, bubble CPAP;
CPAP, continuous positive airway pressure; FiO2, fraction of inspired oxy-
gen; HAB-CPAP, high-amplitude B-CPAP; HFOV, high-frequency oscilla-
tory ventilation; MAP, mean airway pressure; Paw, airway pressure; Pes,
esophageal pressure; PRP, pressure rate product(s); SpO2, pulse oximeter
oxygen saturation(s); WOB, work of breathing
Copyright © 2010 International Pediatric Research Foundation, Inc.
Vol. 67, No. 6, 2010
Printed in U.S.A.
Infant test lung model. We designed an infant airway model consisting of
an infant mannequin head affixed with “leaky” nasal prongs (Fig. 1A insert)
to evaluate the effects of pressure oscillations on gas volume delivered to a
test lung during HAB-CPAP (Fig. 1A). The infant airway model was con-
nected in series to an infant test lung placed inside a plethysmograph. The test
lung compliance and resistance were 0.53 mL/cm H2O and 185 cm H2O/L/s,
respectively. The methods and descriptions used to determine mechanics, leak
magnitude of the prongs, and calibration of the plethysmograph are described
in an online supplement (http://links.lww.com/PDR/A58). Outputs from the
airway pressure (Paw), plethysmograph pressure, and differential pressure
(bias flow) transducers were recorded on a personal computer. The percent-
ages of bias flows leaking around the nasal prongs at a MAP of 7 cm H2O and
bias flows of 4, 6, 8, and 10 L/min were 80.6, 53.7, 40.3, and 32.2%,
The amplitudes of ?Pawand ?V delivered to the lung model were
measured while the HAB-CPAP circuit was connected directly to the lung
model without a nasal interface, at a bias flow of 6 L/min, and with bubbler
angles ranging from 0 to 180°. In addition, amplitudes of oscillations were
measured with the HAB-CPAP circuit attached to the infant airway model via
nasal prongs, and bubbler was depth adjusted to control MAP at 7.0 ? 0.1 cm
H2O, with bias flows of 2 to 12 L/min and bubbler angles of 0, 90, and 135°.
With HAB-CPAP135, bubble motion was recorded at 800 frames/s (Phan-
tom Version9.1; Vision Research, Wayne, NJ) in parallel with a signal
acquisition module (SAM3; Vision Research) to record Pawat 12 kHz and
visualized using CineViewer software (Version 9.1.663.0; Vision Research)
on a desktop personal computer. For visual clarity, clear plastic pieces were
used to collect these data instead of the more opaque pieces used in the other
studies, but the component dimensions of the bubblers were the same, and
pressure wave forms were similar.
Animal model. Under an protocol approved by the Seattle Children’s Research
Institute’s Institutional Animal Care and Use Committee (IACUC), 12 juvenile
female New Zealand white rabbits weighing 1.58 ? 0.02 kg were anesthetized with
After instrumentation, anesthesia was administered continuously as per protocol
(online supplement: http://links.lww.com/PDR/A58). Animals were intubated
orally and ventilated on assist/control mode (Hamilton Medical, Reno, NV) at
30 breaths/min, 0.4 fraction of inspired oxygen (FiO2), 0.35-s inspiratory
time, 4 cm H2O positive end-expiratory pressure (PEEP), and tidal volumes
targeted to 7 mL/kg. The endotracheal tube was tied in place with umbilical
tape to prevent displacement and leakage of gas and saline during lavage.
Pulse oximeter oxygen saturations (SpO2) were measured (Massimo, Irvine,
CA) on the animal’s lower leg. The ventilator respiratory rates (RRs) were
adjusted to maintain PaCO2between 35 and 45 mm Hg.
The FiO2was increased to 1.0, and the lungs were lavaged four times with
30 mL/kg of normal (0.9%) saline warmed to body temperature, with 5-min
recoveries between lavages. Whenever SpO2values were ?92%, additional
lavages were administered. Animals required nomore than six lavages. Ven-
tilation was adjusted to maintain volume target at 5 mL/kg, and PEEP was set
at 6 cm H2O. The RRs were set initially at 60 breaths/min and adjusted
upward to a maximum of 120 breaths/min to maintain PaCO2between 45 to
55 mm Hg. Animals were stabilized on mechanical ventilation for 0.5 h.
Double-lumen esophageal balloon catheters/orogastric tubes were posi-
tioned (Cardinal Healthcare, Dublin, OH) in the lower esophagus and inflated
with 0.4 mL of air. Placement of the catheters was confirmed using the
occlusion technique (7). Esophageal pressure changes (?Pes) were used to
approximate changes in pleural pressures and used in the calculations of
PRPs. The PRP is the product of ?Pesand RR and is used as an index of
inspiratory WOB (8). Abdominal and thoracic Respitrace (Cardinal Health-
care, Dublin, OH) bands were used to confirm the initiation of breaths used in
PRP calculations. The orogastric tube was connected to low intermittent
suction to prevent gastric distention.
The spontaneously breathing animals were weaned to ventilator CPAP of
6 cm H2O and extubated. Custom nasal prongs constructed using silicone
tubing to connect two 4 cm-lengths of 3.0 mm ID endotracheal tubes to a
plastic “Y” and to an endotracheal tube adapter (3.0 mm ID–15 mm OD) (Fig.
1B insert) were fitted and attached to the ventilator. Airway patency through
the nasal prongs was confirmed using end-tidal carbon dioxide monitoring
(Microstream; Oridion, Needham, MA). FiO2, measured with an in-line O2
analyzer (MaxO2plus; Cardinal Health, Dublin, OH), and CPAP were
adjusted to provide SpO2between 85 and 92%. A customized chin strap, as
commonly applied in infants receiving nCPAP (9), was adapted to prevent
large volumes of gas from leaking through the mouth.
After a stabilization period of 30 min on ventilator nCPAP, arterial blood
gas analyses (ABG), MAP, and arterial blood pressures were measured. Each
animal was then randomized using a crossover sequence to the HAB-CPAP at
bubbler configurations of 0, 90, and 135° (Fig. 2A), with the same MAP,
system bias flow, and FiO2established during ventilator nCPAP. ABG, Paw,
Pes, Respitrace, and arterial blood pressure were recorded at the end of each
15-min period of support.
Analyses. An algorithm was developed to estimate ?Pawand ?V delivered
to the infant lung model and to determine the frequency of oscillations with
the greatest magnitude (dominant frequencies), and bandwidth of oscillations.
Methods for estimating amplitude and frequency of ?Pawand ?V are detailed
in the online Supplement (http://links.lww.com/PDR/A58).
Statistics. Data are expressed as mean ? SEM. Data from the bench
studies were assessed by one- or two-way ANOVA, with Newman-Keuls tests
post hoc. Data from studies in rabbits were assessed by pairwise comparisons
for repeated-measures ANOVA model, adjusted for period, with Bonferroni’s
adjustments for the multiple comparisons. Statistical differences are indicated
at p ? 0.05.
Figure 2. Effect of bubbler angle on volumes delivered to test lung by
HAB-CPAP. Data are mean ? SEM for 8 s of recorded data with bias flow
of 6 L/min and no nasal interface or leak. Data were analyzed with one-way
ANOVA, with Newman-Keuls post hoc. Data not sharing common symbols
are different from each other, p ? 0.05.
Figure 1. HAB-CPAP device and study
systems. The system in 1A was used for
testing in vitro and in 1B was used for
supporting rabbits in vivo through nasal
prongs. The configuration with the bubbler
straight down (labeled 0°) is equivalent to
conventional bubble CPAP. The bubblers
were also configured at angles of 90 and
135°, as indicated; PC, personal computer;
A/D converter, analog to digital converter.
HIGH-AMPLITUDE BUBBLE CPAP
Bench studies. Adjusting bubbler angle greatly affected
?Pawand ?V delivered to the test lung. The ?V did not
change when the bubbler angle was increased from 0 through
67°, increased markedly from 67 through 135°, and plateaued
at angles from 135 to 180° (Fig. 2). Ventilating through nasal
prongs attached to the infant airway model also resulted in
increases in ?Pawand ?V as bubbler angles were increased
from 0 to 90° and 135° (Fig. 3A–C). With HAB-CPAP0, ?Paw
was 1.2 ?.1 cm H2O (Fig. 3A) with a dominant frequency of
10.2 Hz (Fig. 3D). With HAB-CPAP90, ?Pawwas 3.6 ? 0.0
cm H2O (Fig. 3B) with a dominant frequency of 1.4 Hz (Fig.
3E). However, additional superimposed oscillations of 1.7 ?
0.0 cm H2O at a dominant frequency near 10.8 Hz were noted,
resulting in an overall average ?Pawof 1.8 ? 0.1 cm H2O.
With HAB-CPAP135, ?Pawwas 4.5 ? 0.5 cm H2O (Fig. 3C),
with a dominant frequency of 3.1 Hz (Fig. 3F). The depths of
below the water surface were 6.9, 5.3, and 2.4 cm at HAB-
CPAP0, HAB-CPAP90, and HAB-CPAP135, respectively.
The effects of bias flow on ?Pawand ?V were not as great
as the effects of bubbler angle. At a bias flow of 2 L/min, the
MAP was 2.2 cm H2O at all bubbler depths ?2.2 cm below
the water surface. All gas flowed through the leak around the
nasal prongs, and none exited through the bubbler. Thus, at
bias flows ?2 L/min, the values for ?Pawand ?V were 0 at all
bubbler configurations (Fig. 4). During HAB-CPAP0 and
HAB-CPAP90, increasing the bias flow from 4 to 12 L/min
had only modest effects on the magnitude of ?Pawand did not
result in appreciable differences in ?V. However, with HAB-
CPAP135, relatively large increases in ?Pawand ?V were
observed as bias flows were increased from 2 to 6 L/min, with
little changes thereafter (Fig 4A and B, respectively). At bias
flows from 4 through 12 L/min, ?Pawand ?V were markedly
higher with HAB-CPAP135 than with HAB-CPAP90 or HAB-
Figure 3. Airway pressure (A, B, and C)
and power spectral analyses of airway
pressure (D, E, and F) while connected to
the silastic test lung at a bias flow setting
of 8 L/min recorded over 8 s.
Figure 4. Effects of bias flow on Pawand volumes delivered to the infant
head model and test lung at the three bubbler angles shown. Measurements
were made at the respective bias flow settings at bubbler angles of 0 (?), 90
(?), and 135° (?). Each data point is the mean ? SEM, for three separate 8-s
Figure 5. Correlation of Pawwith frames of high-speed videos showing the
successive positions of the gas/water interface in the HAB-CPAP135 bubbler.
Point A represents the maximum Pawobserved at the time when the gas/water
interface just enters the horizontal piece. There is a gradual decrease in Pawas
the contiguous bubble progresses up the 135° portion of the bubbler (Point B).
As the gas exits, water reenters the bubbler resulting in relatively high-
frequency oscillations in Paw(Point C).
DIBLASI ET AL.
CPAP0 (Fig. 4). In most testing conditions, increasing bias flow
raised the dominant frequency and bandwidths of ?Paw.
High speed videos showed water oscillating in the bubbler
at frequencies consistent with the fast Fourier transform re-
sults. Figure 5 displays still frames of a typical oscillation
cycle along with a tracing of Paw. At time 0.17 s, Pawrose
rapidly as a bubble formed at the entrance to the horizontal
portion of the bubbler and Pawplateaued as the bubble pro-
gressed along the horizontal portion (Point A). Pawbegan to
decrease when the bubble rounded the corner into the 135°
portion of the bubbler at the time 0.35 s and continued to
decline as the bubble rose in the bubbler (Point B), sustaining
a column of gas still continuous with the airway. Pawwas
minimal when the contiguous bubble expanded to maximum
height, just beyond the tip of the bubbler, at time 0.57 s. As the
rising bubble separated from the bubbler, water rushing into
the bubbler interrupted the gas flow in a somewhat chaotic
fashion (Point C) concomitant with high-frequency ?Paw
followed by the initiation of another cycle near the time 0.63 s.
Animal studies. Lavaging decreased lung compliances in
rabbits from 1.22 ? 0.06 to 0.55 ? 0.03 mL/cm H2O (p ?
0.001). The MAP established for each animal on ventilator
CPAP were applied in the subsequent studies with HAB-
CPAP. No differences were observed in heart rate (p ? 0.75) or
arterial blood pressure (p ? 0.60), when the animals were
managed at the different bubbler angle configurations (Table 1).
Before randomization, the animals exhibited a range of
respiratory compromise, with oxygenation index (OI) ranging
from 1.7 to 10.6 and FiO2ranging from 0.25 to 0.70 (Table 1);
however, all animals were able to be managed appropriately
with HAB-CPAP. The PaO2levels were slightly higher (p ?
0.007) with HAB-CPAP135 and B-CPAP90 than with HAB-
CPAP0 (Fig. 6A). PaCO2levels among treatment groups were
not different (p ? 0.073; Fig. 6B). The PRP values were lower
(p ? 0.001) during HAB-CPAP135 than during the other
bubbler configurations (Fig. 6C). During HAB-CPAP135, two
of the animals (animals 4 and 9) with normal PaCO2(41 and
49 mm Hg, respectively) and vital signs stopped spontaneous
respiratory efforts. Even with omission of the PRP data from
these apneic animals, PRP for the animals on HAB-CPAP135
were lower than on the other HAB-CPAP configurations (data
not shown). RR during HAB-CPAP135 were lower than with
HAB-CPAP90 (p ? 0.030), but not different (p ? 0.068) from
RR with HAB-CPAP0 (Table 2). The levels of ?Peswere
lower during HAB-CPAP135 than during HAB-CPAP0 (p ?
0.006) or HAB-CPAP90 (p ? 0.015), and the levels of ?Pes
at HAB-CPAP0 and HAB-CPAP90 did not differ (Table 2).
The sequence of support of individual animals with HAB-
CPAP0, HAB-CPAP90, or HAB-CPAP135 and the respec-
tive OI are listed in the online supplement (Table S1:
http://links.lww.com/PDR/A58). No animals developed
pneumothoraces or gastric insufflation that might result in
Figure 6. Oxygenation (A), ventilation (B), and indices of WOB using PRP (C) in lavaged rabbits supported by HAB-CPAP. MAP and FiO2were held constant
during the measurements of each animal. p ? 0.05.
Table 1. Physiologic parameters of lung-lavaged rabbits supported by ventilator nasal CPAP before to randomization to HAB-CPAP
(mm Hg) pH OI
CPAP levels were adjusted by the depth of immersion of the bubbler in the water column and were defined as MAP monitored proximal to the nasal interface.
HR, heart rate; BP, blood pressure.
HIGH-AMPLITUDE BUBBLE CPAP
abdominal distension, while being supported with any of
the HAB-CPAP configurations.
The level of noninvasive respiratory support provided to
spontaneously breathing lung lavaged juvenile rabbits during
HAB-CPAP135 (Fig. 6) suggest that HAB-CPAP may be able
to extend the range of premature infants who can be managed
successfully with B-CPAP. In addition, the effects of bubbler
angles between 0 and 180° on ?Pawand ?V observed in
model in vitro studies (Figs. 1–3) suggest a useful mode of
HAB-CPAP adjustment to match the changing or specific
needs of patients as their diseases progress or resolve.
The ?V measured in the static lung model with conven-
tional B-CPAP (HAB-CPAP0) offers an explanation for the
observations of Versmold et al. (10), who reported markedly
slower PaCO2increases in the chemically paralyzed animals
supported by B-CPAP than with ventilator CPAP. Further,
these measurable effects of B-CPAP on ÄV are consistent
with the findings of Lee et al. (11) that B-CPAP in infants
resulted in lower ventilation requirements, with similar blood
gases, than were required with ventilator CPAP.
Attempts to augment the level of respiratory support pro-
vided with B-CPAP have included increasing bias flow that
increases the magnitude and bandwidth of ?Pawdelivered to a
test lung via nasal prongs (12). Greater ?Pawshould provide
greater alveolar recruitment, gas exchange, and reduce WOB.
The modest differences in ?V to a lung model resulting from
increased bias flows observed with HAB-CPAP0, during our
studies in vitro, are consistent with the findings of Pillow et al.
(4) and Morley et al. (12), who observed no physiologic
benefits using higher bias flow settings in spontaneously
breathing subjects supported by B-CPAP.
Nekvasil et al. (13) attempted to augment the level of ?Paw
using a B-CPAP system consisting of a funnel with the stem
positioned at 90° as the underwater seal. They applied this
device in three intubated neonates and found that short-term
gas exchange was similar to high-frequency ventilation when
applied to the same neonates. None of the infants became
apneic when using this B-CPAP system, whereas instances of
apnea or severe bradypnea were observed during high-
frequency ventilation. During the in vitro studies, Nekvasil et
al. (13) also used ethanol and glycerin in the bubbler and
noted that the frequencies of oscillation in Pawwere inversely
related to densities of the liquid. The physical properties of the
bath liquid clearly can influence system function parameters,
but water-based liquids are favored by practical and potential
The forces required to reverse the direction of flow of the
water as it reenters the bubbler, after the release of a bubble,
and then to accelerate the water into the horizontal portion of
the bubbler (Fig. 5) can account for the high ?Pawobserved
during HAB-CPAP135. Estimations of surface tension forces
in the bubbler by LaPlace equation calculations suggest that
such effects on ?Paware minor. Low points in Pawwere
observed when the column of gas contiguous with the airway
rose to highest point in or just beyond the end of the bubbler.
The breakup of the air column in the bubbler was associated
with higher frequency and lower amplitude ?Pawthan those
were observed during formation and expansion of the bubble
contiguous with the airway. Kulkarni and Joshi (14) reported
similar rapid depressurization immediately preceding detach-
ment of bubbles from a submerged orifice. Many of these
relatively small ?Paware included in our algorithm used to
calculate overall ?Paw, resulting in a lower, more conserva-
tive, estimates of the mean values of ?Paw.
The lower frequencies of ?Pawduring HAB-CPAP135
allow more time for volume delivery to the lung model than is
observed with HAB-CPAP0 and during most applications of
high-frequency oscillatory ventilation (HFOV) in preterm in-
fants. It is interesting to note that tidal volumes of 2 to 3 mL,
delivered to our lung model through leaky nasal prongs during
nasal HAB-CPAP135, approximated the volumes measured in
infants intubated endotracheally and receiving HFOV (15).
We do not know the differences in lung mechanics between
the mechanical test lung and the premature infants on HFOV.
However, the resistance to gas flow in binasal short prongs is
a fraction of the resistance of endotracheal tubes used in
preterm infants (16), which very likely contributes to the
similarities in delivered tidal volumes. These tidal volumes,
although small, may contribute to gas exchange through direct
bulk alveolar ventilation. The high-frequency oscillations ob-
served during HAB-CPAP135 may also retain the benefits of
HFOV that have been attributed to enhanced gas diffusion and
lung recruitment with tidal volumes at or below the anatomic
dead space (17).
Conventional high-frequency ventilators are capable of de-
livering very high ?Pawbut operate at a single frequency,
whereas HAB-CPAP135 provides lower dominant frequen-
cies at broad bandwidths of associated intensities. Diseased
lungs are remarkably heterogeneous (18), and the spectra of
pressure frequencies produced by HAB-CPAP135 may be
more effective than the high-frequency ventilators to comple-
ment the array of airspaces that need ventilatory support.
Improvements in PaO2in the animals during HAB-
CPAP135 may reflect alveolar recruitment from Pawoscilla-
tions at broadband frequencies superimposed on the sponta-
neous breathing efforts. Biologically variable ventilation
applies variations in tidal volume and respiratory frequency
settings similar to normal variations in the human breathing
pattern. In lung-injured animals, biologically variable ventila-
tion has been shown to improve gas exchange, lung mechanics
(19), and endogenous surfactant production (20) better than
conventional volume-cycled ventilation. Suki and coworkers
(21–23) attributed these physiologic effects to stochastic reso-
nance, which describes the complex relationship of lung stability
Table 2. Physiologic breathing parameters for lung-lavaged
rabbits supported by HAB-CPAP
3.7 ? 0.5†
3.5 ? 0.5†
2.4 ? 0.6
289 ? 30§
303 ? 35§
141 ? 28
088.1 ? 9.8*‡
92.6 ? 8.6‡
58.9 ? 11.2*
§ Data are means ? SEM. Values not sharing the same superscript symbol
differ, p ? 0.05.
DIBLASI ET AL.