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1 Portex Anaesthesia, During recent years
it has been suggested that forced expiratory measurements, derived from
a lung volume set by a standardized inflation pressure, are more
reproducible than those attained during tidal breathing when the rapid
thoracoabdominal compression technique is used in infants. The aim of
this study was to evaluate the feasibility of obtaining measurements
from raised lung volumes in unsedated preterm infants. Measurements
were made in 18 infants (gestational age 26-35 wk, postnatal age
1-10 wk, test weight 1.4-3.5 kg). Several inflations
[1.5-2.5 kPa (15-25
cmH2O)] were used to briefly
inhibit respiratory effort before the rapid thoracoabdominal compression was performed. Conventional analysis of flows and volumes
at fixed times and percentages of the forced expiration resulted in a
relatively high variability in this population. However, by using the
elastic equilibrium point (i.e., the passively determined lung volume,
derived from passive expirations before the forced expiration) as a
volume landmark, it was feasible to achieve reproducible results in
unsedated preterm infants, despite their strong respiratory reflexes
and rapid respiratory rates. Because this approach is independent of
changes in expiratory time, expired volume, or applied pressures, it
may facilitate investigation of the effects of growth, development, and
disease on airway function in infants, particularly during the first
weeks of life, when conventional analysis of forced expirations may be inappropriate.
airway function; rapid thoracoabdominal compression technique; raised-volume technique; respiratory function tests
FORCED EXPIRATORY MANEUVERS are routinely used to
measure airway function in infants for clinical and research purposes
(13). Although infants cannot be instructed to perform such maneuvers, they can be encouraged to breathe out as rapidly as possible through a
face mask and pneumotachometer (PNT) by sudden application of a
compressive pressure at end-tidal inspiration using an inflatable plastic cuff or jacket wrapped around the thorax and abdomen (13, 18,
19). Maximal flow at functional residual capacity
( During the past few years, a new approach, known as the raised-volume
RTC (RVRTC) technique, has been introduced. This technique assesses
airway function over an extended volume range by delivering one (21) or
a few (4, 10) large sighlike breaths to elevate lung volume before the
RTC. Potentially, this enables full forced expiratory flow-volume
curves, similar to those performed voluntarily by children and adults,
to be obtained in infants. However, this technique has only been
applied to sedated full-term infants beyond the neonatal period. The
use of sedation is generally contraindicated for lung function tests in
spontaneously breathing infants <44 wk postconceptional age (7).
This, together with the short epochs of natural, quiet sleep, frequent
feeds, rapid and irregular breathing patterns, and strong respiratory
reflexes, makes assessment of airway function notoriously difficult in
preterm infants. There is, however, a real need for information about
the growth and development of the respiratory system in late gestation
and early postnatal life and the effects of disease and response to
therapy during this period. Measurement of full forced expiratory
flow-volume maneuvers could potentially provide such information. The
aim of this study was therefore to evaluate the feasibility of using the raised lung volume technique to assess airway function in unsedated
preterm infants.
Subjects.
Infants were recruited from the Neonatal Unit at the Homerton Hospital,
Hackney, East London. Measurements were performed in 8 female and 10 male infants at 32-38 wk postconceptional age (postconceptional
age = gestational age + postnatal age). Five of these infants had had
no respiratory support, 10 had received assisted ventilation
and/or supplementary oxygen for up to 5 days, and the remaining
3 were ventilated for >5 days and had received supplementary oxygen
for >4 wk. Infant details are summarized in Table
1. All infants were studied unsedated,
0.5-1 h after a feed, during natural quiet sleep without
additional oxygen. Respiratory measurements were obtained with infants
settled in the supine position, while heart rate, oxygen saturation,
and end-tidal CO2 were monitored.
The study was approved by the East London and City Research Ethics
Committee. Informed written consent was obtained from the parents, who
were usually present throughout the measurements.
ABSTRACT
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
maxFRC), measured by this rapid thoracoabdominal compression (RTC), or squeeze,
technique, is taken as an index of small airway function. Nevertheless,
despite its value, this test has provided less information about
respiratory problems in infants than similar tests in older children
and adults (1). This is partly because tests in infants are limited to
those that can be measured during normal tidal breathing, whereas
standard tests in adults and children are made over the full vital capacity.
MATERIALS AND METHODS
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Abstract
Introduction
Materials & Methods
Results
Discussion
References
Table 1.
Infant details
Equipment and data acquisition. A transparent Rendell-Baker face mask (size 0, Ambu International, Bath, Avon, UK) was held over the infant's mouth and nose, and a leak-free seal was created using therapeutic silicone putty (Carters, Bridgend, Mid Glamorgan, Wales). Flow was measured with a heated PNT (model 3500, Hans Rudolph, Kansas City, MO; dead space 6.8 ml, linearity 0-35 l/min) connected to a ±0.2-kPa (2-cmH2O) differential pressure transducer (Furness Controls, Bexhill, East Sussex, UK). Volume was obtained by digital integration of the flow signal.
Partial expiratory flow-volume curves were obtained as described in detail previously (17). Forced expiration was generated by inflating a jacket, which was wrapped snugly around the infant's torso with the arms outside. The jacket extended from under the infant's axillae to the iliac crest. The jacket consisted of a 17 × 16-cm polythene inflatable plate surrounded by a stiff outer fabric covering and was rapidly inflated from a 100-liter pressurized reservoir connected to the inflatable plate by a rigid large-bore (28-mm-ID) section of tubing. Pressure at the airway opening and jacket pressure were measured with ±5- and 10-kPa (50- and 100-cmH2O) differential pressure transducers, respectively (Furness Controls). Esophageal pressure (Pes) was recorded throughout the test in seven of the infants by using a microtip pressure transducer catheter (model 3FG, Draëger) (5). This catheter was inserted nasally into the distal third of the esophagus, and an occlusion test was performed to validate its accurate functioning (2). Flow and pressure signals were amplified and filtered above 10 Hz. Analog signals were digitized at 200 Hz (RASP, Physiologic, Newbury, Berks, UK) and stored on an IBM-compatible 486 personal computer.Special features for the RVRTC technique.
The equipment (Fig. 1) was adapted from
that described by Feher et al. (4). The PNT was attached to a
mainstream capnograph (CO2SMO,
model 7100, Novametrics Medical Systems, Wallingford, CT) and connected
to a Y piece (total resistance 0.570 kPa · l
1 · s
at a flow of 100 ml/s). The inspiratory side of the Y piece (3-way
connector) received a constant airflow at 12 l/min via a pressure
relief valve (Neopuff, model RD1000, Fisher and Paykel Healthcare,
Auckland, New Zealand), which was set to 1.5-2.5 kPa (15-25
cmH2O).
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Study protocol.
The study commenced with measurements of
maxFRC using
the standard RTC maneuver (13, 17). Real-time signals of flow, volume,
and pressure were displayed as time-based and
x-y plots. Once 5-10 regular
breaths had been recorded, the jacket was inflated at end inspiration
to force expiration. Jacket pressure commenced at 2 kPa, then was
increased at 0.5- to 1-kPa increments until flow at functional residual
capacity (FRC) had reached a reproducible maximum (i.e.,
maxFRC) and
higher pressures were causing a reduction of flow, indicating that
apparent flow limitation had been achieved. At least three assessments
of static jacket pressure transmission were performed at end-tidal
inspiration (15).
maxFRC during
tidal maneuvers was then used during the raised-volume maneuvers. Measurements at raised lung volumes commenced with the pressure valve
for the passive inflations set to 2 kPa (20 cmH2O). To ensure that no
additional dead space was presented to the infant, manual inflations
began immediately on connection of the capnograph and Y piece to the
apparatus. Repeated occlusions of the expiratory side of the Y piece at
a frequency approximating the infant's respiratory rate resulted in
passive inflations and deflations of the respiratory system (Fig.
2). Respiratory muscle relaxation was
indicated by a change in Pes from negative deflections during active
inspiration to positive inflections during passive inflations or from
inspection of the flow-volume loops if no Pes trace was available. Once
such relaxation had been achieved, the jacket was inflated at the end
of a passive inflation to force expiration. Whenever possible,
additional RVRTC maneuvers were also obtained at inflation pressures of
1.5 and 2.5 kPa (15 and 25 cmH2O).
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Data analysis.
The analysis software package was developed in collaboration with the
Imperial College of Science, Technology, and Medicine. Criteria for
acceptability of forced expiratory flow-volume curves were as follows:
1) jacket inflation initiated within
100 ms of end inspiration, 2) peak
expiratory flow achieved before 50% of previous tidal or passive
inflation volume had been expired,
3) expiration proceeding beyond end
expiratory level, and 4) regular tidal volume and end-expiratory level for the standard RTC or regular
relaxed inflations for the RVRTC, as assessed by visual inspection of
the time-based and flow-volume traces. Exclusion criteria included
1) leaks through face mask, PNT, or
jacket and 2) significant glottic
closure or flow transients. The mean of the three best flows at FRC
from technically acceptable curves was calculated and reported as
maxFRC.
Raised-volume data analysis. Initially all RVRTC data were analyzed in the conventional manner using only technically acceptable maneuvers that had a forced expired volume (FEV) within 10% of the highest value obtained (4). The following parameters were calculated: forced expiratory flows and volumes at 0.4, 0.75, and 1 s (FEFt and FEVt, respectively) (21) and forced expired flows at fixed percentages of the FEV (4) (e.g., MEF50 and MEF25, where MEF is the maximal expired flow when 50 or 25% of expired volume remains in the lung, i.e., equivalent to FEF50 and FEF75, respectively).
Inspection of preliminary data revealed that conventional analysis at fixed times or percentages of expired volume resulted in rather variable results in this population (Fig. 3A). This was largely due to subtle variations in the inflation volume and the expired volume, resulting in an inability to superimpose the FEF with any consistency. The following approach was therefore developed in an attempt to find a more reliable volume landmark with which to relate forced flows and volumes in this population.
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45%) of the
expiratory loop before the RTC. Provided the coefficient of
determination
(r2) was
0.98, the program then added the data from the same segment of the
previous passive breath to the regression model and reassessed the
correlation. This procedure was repeated for an increasing number of
breaths before the forced maneuver until the correlation fell below the
specified threshold. The process was repeated for each forced maneuver.
The program also provided the means to overlay the flow-volume loops
from a number of separate RVRTC maneuvers by superimposing the
individual pairs of curves (one passive breath with the ensembled time
constant and its associated forced maneuver) and shifting them along
the volume axis so that they were aligned at their calculated EEV (Fig.
3C). FEF could then be calculated at
any number of user-specified points above or below the EEV. In the event of an acceptable forced expiratory maneuver but a poor-quality passive deflation immediately beforehand, which precluded accurate determination of the EEV for that trial, the program permitted manual
realignment along the volume axis with respect to previously analyzed
data. This option was utilized only if it resulted in clear
superimposition of the descending portion of the forced expiratory curves.
To facilitate comparisons between infants of different weights and
ages, we chose to standardize the volume above EEV at which flows
should be calculated with respect to the infant's weight. This was
believed to be justified, since there is a strong linear relationship
between both tidal volume and compliance and body weight during infancy
(14, 16). For clarity, only those values calculated at 2 and 4 ml/kg
are reported here (Fig. 3C). These points were selected as examples to facilitate comparisons with maxFRC, since
it is recognized that young infants usually dynamically elevate their
FRC by 2-4 ml/kg above their passively determined lung volume (11,
12).
Thus, after alignment of all the individual raised lung volume
maneuvers, FEF at EEV (FEEV) and
at 2 and 4 ml/kg body weight above EEV
(FEEV + 2 and
FEEV + 4) were
calculated (Fig. 3C). The aim was to
superimpose at least three acceptable curves for each infant.
Reproducibility. In those infants in whom at least three technically acceptable measurements were available, the reproducibility of the different analytic approaches was compared by calculating the coefficient of variation [coefficient of variation = 100 × (SD/mean)] based on three determinations for each parameter.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Forced expiratory maneuvers during tidal breathing and raised volumes were obtained in all 18 infants. Between three and nine (median 5) inflations were required to achieve respiratory muscle relaxation before the raised-volume maneuver. No adverse effects were observed. The augmentation of ventilation produced a temporary fall in end-tidal CO2 by 0.2-0.9 kPa from baseline levels. After the RVRTC maneuver the maximum time taken to resume spontaneous respiration was 15 s. Jacket pressure was 4.1 ± 1.1 (SD) kPa, with a mean jacket pressure transmission of 45% (range 33-55%).
Causes of failure. Of the 4-25 RVRTC maneuvers performed in each infant (median 14) only 40% were technically acceptable. Major reasons for failure were late glottic closure, flow transients, and early inspiration (Fig. 4), the latter often related to the difficulties in invoking respiratory muscle relaxation in this population. No technically acceptable data were obtained in two infants and another had fewer than three acceptable curves, thereby precluding reporting of results. Acceptance of only those curves with an FEV within 10% of the highest value resulted in exclusion of another two infants. Among the total population of 18 infants, only 5 continued to expire beyond 0.7 s and only one beyond 1 s, thereby precluding analysis of forced volumes and flows at these longer time intervals.
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Reproducibility.
Results from the remaining 13 infants who had three technically
acceptable RVRTC curves with an FEV within 10% of the highest value
are summarized in Table 2. For each infant
the individual mean data, along with coefficients of variation, are
shown only for those parameters where it was possible to obtain three
technically satisfactory measurements. Thus no results are shown for
maxFRC in three
infants in whom only two satisfactory tidal maneuvers could be obtained
or for FEF and FEV at 0.4 s in the seven infants who did not
consistently expire beyond 0.4 s. The variability of
FEEV + 2 was generally
lower than that of other parameters with similar flows, e.g.,
maxFRC and
MEF25.
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Influence of changes in inflation pressure. Technically acceptable RVRTC data were obtained at different inflation pressures in 10 infants. As expected (21), forced flows and volumes at fixed times and percentages of the expired breath were dependent on the applied inflation pressures, higher values being achieved as pressures were increased (data not shown). By contrast, similar values of FEEV, FEEV + 2, and FEEV + 4 were obtained, irrespective of the applied pressures (Fig. 5).
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Influence of timing of the raised-volume maneuvers. When the maneuvers were aligned along the volume axis according to the EEV, data previously deemed unacceptable due to methodological problems such as late jacket inflations, late release of inflation pressure, or early glottic closure were found to be readily superimposable (Fig. 6).
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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In contrast to FEF measurements from raised volumes in older infants (4, 21), we experienced considerable technical and analytic problems and a high failure rate when applying this technique to a population of preterm infants during the first 3 mo of life. Consequently, when the infant remained asleep for long enough, it was necessary to perform a large number of maneuvers in an attempt to achieve three reproducible maneuvers within individual infants. However, by adapting the analytic technique so that the EEV, rather than the volume achieved from a preset pressure, was used as a volume landmark, we overcame many of these problems.
Methodological aspects. When the raised lung volume technique is applied to premature infants, several important methodological considerations must be taken into account. In contrast to measurements during tidal breathing, peak flows >400 ml/s may be achieved during the RVRTC, even in infants with a history of chronic lung disease. This precludes the use of a PNT with a very low dead space, which would normally be selected for this population. The PNT employed in this study had a dead space of ~3 ml/kg to ensure an adequate linear range. This did not appear to have any adverse effects, and respiratory rates during spontaneous breathing were similar to those observed when a smaller device was used. Nevertheless, the application of techniques that can generate such high flows in such small subjects presents a challenge for manufacturers in the future.
In this study we were cautious not to expose the infants to excessive pressures in view of their immaturity and highly compliant airways and chest wall. During the initial pilot studies we attempted to use inflation pressures as low as 1.5 kPa but found that this rarely induced the desired relaxation (see below). Similarly, although we recognized the need to estimate the percentage of jacket pressure transmitted during the forcing maneuver, we preferred to perform this assessment at end-tidal inspiration, rather than after inflation to raised lung volume, to limit the pressures (elastic recoil pressure plus transmitted jacket pressure) to which the infant was exposed. Hayden and colleagues (10) showed that most outcome variables are pressure independent at a transmitted pressure between 2 and 2.5 kPa. For the raised-volume maneuvers, the use of the lowest jacket pressure required to achievemaxFRC during
tidal maneuvers was selected in accordance with the protocol of the
same group (21). The mean lowest jacket pressure required to achieve
maxFRC
in this study was 4.1 kPa, with a mean pressure transmission of 45%,
such that the transmitted pressure to the intrathoracic structures was
~2 kPa at end-tidal inspiration. This should be sufficient to achieve
flow limitation (10), especially in this population of preterm infants,
many of whom had had respiratory problems at birth. The absolute
driving pressures at higher lung volumes would have been even higher
because of the increased recoil pressure of the lungs. Use of higher
jacket pressures not only evokes excessive glottic closure in this
population but can result in marked negative pressure dependency, which
we were anxious to avoid.
Relative reproducibility. There are considerable difficulties in attempting to evaluate comparative reproducibility of different analytic techniques for forced expiratory maneuvers, since the calculated values will depend on prior exclusion criteria, the number of maneuvers analyzed, the absolute magnitude of the reported values, and indeed whether parameters are based on flow or volume. Because volume is the integral of flow, measures such as FEVt will always be less variable than those based on flow. Furthermore, any comparison of group mean data will be biased if there are missing data for different parameters in different subjects. In an attempt to address some of these issues, we based all calculations of reproducibility on three maneuvers, excluded those results where fewer data were available, and reported individual results for each infant (Table 2).
Estimation of EEV. In this study, EEV was estimated by extrapolating the linear descending portion of the passive expiratory flow-volume loop, i.e., the expiratory time constant. The accuracy of this approach was improved by calculating the ensembled time constant from several passive breaths before each forced maneuver. In addition to the achievement of complete muscle relaxation, a major assumption of this approach is that the respiratory system can be represented by a single time constant. We are confident that relaxation had been attained in the infants in whom data were accepted for analysis, although this was not necessarily achieved in every breath in every infant. Occasionally, despite having achieved relaxation, some intermittent spontaneous respiratory activity resumed. This was particularly marked if a longer expiratory pause was provided in the breath immediately before the jacket inflation, in an attempt to allow the infant to exhale more completely. This did not necessarily invalidate the forced expiratory maneuver but did necessitate calculating the passive time constant from an earlier breath in the sequence. We have subsequently revised our protocol so that attempts to achieve complete passive expiration are recorded during trials separate from those in which forced expiratory maneuvers are performed.
The assumption of a single time constant is more complex, particularly if this approach is to be used to assess airway function in infants with elevated airway resistance. In such infants a rise in resistance toward end expiration could lengthen the time constant over the latter portion of the expiratory flow-volume curve, causing overestimation of the volume intercept and, hence, errors in the calculated EEV (3, 6). Although it was not possible to obtain a linear relaxed curve from every infant during every maneuver, extrapolation of passive flow-volume curves from raised volumes proved far less problematic in this study than when a similar approach was attempted after end-inspiratory occlusions during tidal breathing (i.e., the single-breath technique) (6). Results were accepted only if a time constant with r2 0.98 could be calculated over 45% of the expired volume toward end expiration (a portion that represented well over 75% of the duration of expiration in most of these infants). We found that extrapolation of this portion of the curve coincided with complete expiration to passive resting lung volume in those infants in whom this
could be achieved (Fig. 7). The curvilinear
appearance of the initial portion of the passive curves was usually
attributable to flow transients that occur during early expiration on
release of an airway occlusion as a result of gas decompression through the PNT (Figs. 7 and 8), the magnitude of
which is dependent, at least partially, on the speed at which the
occlusion is released. This portion of the curve was always excluded
when the time constant was estimated.
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maxFRC obtained
during tidal RTC maneuvers in each infant, thereby facilitating
comparisons of relative reproducibility. In addition, it was always
possible to superimpose the forced expiratory curves at these points.
Values for FEEV + 4, which were similar to MEF25 in the
majority of infants, were routinely available in all infants. However,
further work is required to ascertain which indexes prove to have the
greatest sensitivity and specificity in detecting airway disease or
response to therapy in this age group. In several of the infants,
reproducible forced flows could also be obtained at much higher lung
volumes (e.g., up to
FEEV + 9 in Fig. 5).
However, in the absence of automatic equipment to improve timing of
jacket inflations and release of airway occlusions and in the presence
of frequent glottic closure in response to the jacket inflation, it was
not possible to routinely achieve reproducible flows at high lung volumes in these infants.
In this study we followed the approach of Feher et al. (4) and analyzed
only curves that were within 10% of the highest value obtained. Not
only did this increase the failure rate of the technique, but we still
observed considerable variability with respect to forced flows and
volumes at fixed times or percentages of the expired breath. This was
primarily due to the fact that although we selected breaths in which
overall volume change was similar, there were subtle differences in the
volume delivered at any given pressure and the volume expired.
Variations in inflation volume occur when preset pressures are used, if
there is any variability in the duration of inflations or respiratory
mechanics, whereas variations in expired volume result from
differences in inflation volume and duration of expiration, with
young infants frequently making inspiratory efforts before residual
volume has been achieved. Circumstances can thus arise whereby a
slightly smaller inflation volume coupled with a longer duration of
expiration may give a FEV similar to that achieved with a larger
inflation volume but earlier inspiration. Under these circumstances,
the flows obtained at fixed times or percentages of the FEV will vary,
as found in the current study (Fig.
3A). Achieving consistency of
applied pressures or volumes can also be a problem in older infants,
with some centers applying regression analysis to a range of pressures to calculate results (21).
In conclusion, although further refinements are required, particularly
with respect to estimating the EEV more objectively, the use of EEV as
a volume landmark appears to be a promising approach when the
raised-volume technique is applied to young or sick infants in whom
sedation may be inappropriate (8) but in whom a knowledge of airway
growth and development is very important. Furthermore, this may not
only facilitate the achievement of more reliable results in this age
group but provide a means to compare data within and between centers
until a more standardized approach to data collection and analysis has
been developed. However, further refinements are required, particularly
with respect to suitable automation for use in such rapidly breathing
subjects. In addition, the observation of marked increases in volume
during spontaneous sighs above that achieved by 2.5 kPa of inflation
pressure is of considerable interest. This phenomenon needs systematic
investigation in the future, inasmuch as it suggests that the
determination of total lung capacity may differ between adults and
preterm infants.
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ACKNOWLEDGEMENTS |
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The authors thank Sarah Reid for assistance during this study and Novametrix for supplying the mainstream capnograph.
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FOOTNOTES |
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This study was supported by SIMS Portex, the Foundation for the Study of Infant Deaths, and the Dunhill Medical Trust. M. Henschen was supported by the Deutsche Forschungsgemeinschaft.
Address for reprint requests: M. Henschen, Universitäts-Kinderklinik, Mathildenstrasse 1, 79106 Freiburg, Germany.
Received 8 December 1997; accepted in final form 27 July 1998.
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Abstract
Introduction
Materials & Methods
Results
Discussion
References
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rs)
by least-squares linear regression of descending linear portion of
passive expiratory flow-volume curve of maneuver
a in A. This time
constant was extrapolated to zero flow to obtain elastic equilibrium
volume (EEV). C: realignment of
maneuvers a and
b with respect to their EEV. In
contrast to A, where curves were
superimposed at end inflation to a set pressure, reproducible flows
were obtained up to 6 ml/kg above EEV in this infant when curves were
realigned according to their EEV. For clarity, only 2 maneuvers are
shown, although this process could be performed with as many curves as
desired. EEV + 2 and EEV + 4, flows at 2 and 4 ml/kg above EEV.
