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* From the Department of Anaesthesia/Respiratory Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Correspondence to: Robert M. Kacmarek, PhD, FCCP, Respiratory Care, Ellison 401, Massachusetts General Hospital, Boston, MA 02114
| Abstract |
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), and volume vs time waveforms during partial liquid
ventilation (PLV). Design: Prospective application of PEEP during PLV in a healthy animal model.
Setting: University hospital animal laboratory.
Participants: Five healthy sheep weighing 30 kg each.
Interventions: The sequential application of 0 to 20 cm H2O PEEP in 2.5-cm H2O steps during PLV with both pressure and volume ventilation.
Measurements: Analysis of the pressure,
volume, and
waveforms as PEEP is sequentially increased.
Results: At 0 cm H2O PEEP, VT was
markedly reduced compared with PEEP VT at
7.5 cm
H2O (p < 0.05) in pressure control ventilation (PCV),
and peak inspiratory pressure minus PEEP was markedly increased
compared with PEEP at
5.0 cm H2O (p < 0.05) in
volume control ventilation. At 10 cm H2O PEEP, all
waveforms began to stabilize, and no significant differences in any
variable assessed were measured at > 12.5 cm H2O
PEEP.
Conclusions: The application of PEEP during PLV
markedly alters airway waveforms. Low PEEP decreases VT in
PCV and increases airway pressure in VCV. The PEEP level equal to the
LIP during PLV can be grossly estimated from airway waveforms. PEEP at
10 cm H2O is needed to normalize gas delivery to
functional residual capacity in the uninjured lung that is partially
filled with perfluorocarbon.
Key Words: compliance gas delivery pattern lower inflection point partial liquid ventilation resistance
| Introduction |
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| Materials and Methods |
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Preparation
Five fasted Hampshire sheep ([mean ± SD] body weight,
29.7 ± 3.9 kg) were anesthetized with halothane and were orally
intubated using endotracheal tubes (HiLo Tube; Mallinckrodt Medical,
Inc; St. Louis, MO) that had inner diameters of 9 mm. To ensure gastric
drainage, a 14F orogastric tube (model 15114; Mallinckrodt
Laboratories Ltd; Athelone, Ireland) was inserted for each sheep. After
cannulating the right jugular vein and administering a loading dose of
fentanyl (0.3 mg) and diazepam (10 mg), anesthesia was maintained using
fentanyl (3 µg/kg/h) and sodium pentobarbital (5 mg/kg/h), and
paralysis was established with pancuronium bromide (2 mg/kg/h).
Lactated Ringers solution was administered IV to maintain adequate
intravascular volume. Body temperature was maintained at 39°C by the
use of a heating blanket, and mechanical ventilation was provided (PB
7200 ae ventilator; Nellcor Puritan Bennett; Carlsbad, CA).
Experimental Protocol
Following the preparation of each animal and a stabilization
period of 15 min, each animal was administered perflubron in the supine
position until a meniscus could be observed at the incisors (PEEP, 0 cm
H2O). A total dose of about 30 mL/kg was
administered. Because of the short duration of the study period (< 2
h), no supplemental doses of PFC were given. Based on our prior
experience with this model, we would expect
1 mL/kg of PFC to
evaporate during the study. Each sheep was ventilated using both volume
control ventilation (VCV) and pressure control ventilation (PCV)
applied in random order. In the VCV mode, VT was 10 mL/kg,
respiratory rate was 20 breaths/min, total inspiratory time was
1.5 s (with an inflation hold of 0.7 s), and the flow
(
) pattern was square wave, set at 1 L/min/kg, yielding about 30
L/min on average. In the PCV mode, the inspiratory pressure was
adjusted to deliver a VT of about 10 mL/kg at a set PEEP
level of 10 cm H2O with a respiratory rate of 20
breaths/min and a total inspiratory time of 1.5 s. The fraction of
inspired oxygen was 0.5 throughout the experiment in both PCV and VCV.
In both modes of ventilation, the PEEP was increased sequentially in
2.5-cm H2O increments from 0 to 20 cm
H2O. Following each increase, the animals were
allowed to stabilize for 5 min before measurements were made. Based on
prior experience with this model, ventilatory parameters were set to
ensure that peak alveolar pressures (end-inspiratory plateau pressures
[PPLATs]) were below the upper inflection point on the
P-V curve of the total respiratory system throughout the spectrum of
applied PEEP (Fig 1
). Throughout this evaluation, the end-inspiratory PPLAT
remained at < 35 cm H2O, and no auto-PEEP was
measured in either PCV or VCV at any PEEP setting.
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signal and was reconfirmed with a 500-mL calibrated
syringe. At each setting, we also measured total PEEP with an
end-expiratory hold maneuver (for 5 s) using the auto-PEEP
function of the mechanical ventilator. All signals were amplified
(model 8805C; Hewlett Packard; Waltham, MA) and recorded at 100 Hz
using an analog-to-digital conversion system (WINDAQ/200V1.36; Dataq
Instruments; Hartfield, PA) and a personal computer. All devices were
calibrated at the beginning of the experiment.
A P-V curve of the lung-thorax system was obtained using a calibrated
500-mL syringe to detect the LIP and a 2,000-mL syringe to detect the
upper inflection point (UIP) after partial filling of the lung with
PFC. After the establishment of a volume history to 50 cm
H2O pressure, stepwise 50-mL inflations with a
500-mL syringe and 100-mL inflations with a 2,000-mL syringe were
performed while recording the corresponding airway pressure before the
stepwise sequential application of PEEP in 2.5-cm
H2O increments. We stopped inflation when airway
pressure exceeded 50 cm H2O. The total procedure
lasted
30 s. The lung filled with liquid demonstrated a nonlinear
P-V relationship. The pressures associated with changes in the slope of
the P-V curve were identified as the LIP and UIP. LIP and UIP
were determined from the crossing of tangents applied to the various
slopes of the curve (Fig 1)
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In the VCV mode, peak
, time from initiation of inspiration to
peak
, time from initiation of inspiration to 75% of peak
, peak inspiratory pressure (PIP) minus PEEP, time
from initiation of inspiration to PIP, and end-inspiratory
PPLAT, were recorded at each level of PEEP. Inspiratory
resistance was then calculated as peak pressure minus PPLAT
divided by
, and quasi-static compliance was calculated by
dividing the PPLAT-PEEP by the VT. In the PCV
mode,
, peak pressure minus PEEP, time from initiation of
inspiration to peak
, time from initiation of inspiration to
peak pressure, VT, and peak pressure minus PEEP at peak
were recorded at each level of PEEP. In addition, quasi-static
compliance was calculated by dividing the end-inspiratory pressure
minus PEEP by the VT.
Statistical Analysis
Data were collected from three consecutive breaths at each PEEP
level and were averaged in both PCV and VCV after a 5-min stabilization
period. Overall, data are expressed as mean ± SD as obtained from the
five sheep that were studied. A software package (STATISTICA 5.1;
Statsoft Inc; Tulsa, OK) was used for statistical analysis. Analysis of
variance (ANOVA) for repeated measures was applied to each variable
evaluated in both PCV and VCV. When statistical significance was
reached by ANOVA, a post hoc analysis was performed using
the Schéffe F test. A p value
0.05 was considered
statistically significant.
| Results |
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Waveforms
Figures 2
and
3
illustrate the changes in pressure and
as PEEP increased during
both PCV and VCV. As observed in Figure 2
, the greatest peak airway
pressure above the set PEEP during volume ventilation occurred at 0
PEEP and decreased with each increment of PEEP added (p < 0.05;
Table 1
). In addition, the slope of the airway pressure increase was almost
vertical at a PEEP of 0 cm H2O, decreasing as
PEEP was applied and showing a more normal volume targeted (square wave
) airway pressure waveform at a PEEP
10 cm
H2O.
during VCV (Fig 2)
changed in a
similar manner (p < 0.05; Table 1
), and peak
exceeded set
levels at low PEEP. With the application of
10 cm
H2O PEEP, a more normal square wave
pattern was observed. Both pressure and
waveforms were
consistent with typical gas ventilation with the application of
10
cm H2O PEEP.
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waveforms during PCV are depicted in
Figure 3
. At low or no PEEP, peak airway pressure exceeded the set
level by 5 to 10 cm H2O during the onset of the
inspiratory phase (p < 0.05; Table 2
). However, as PEEP reached
10 cm H2O, a more
normal airway pressure waveform was observed, with initial pressure
nonsignificantly decreasing as PEEP was further increased from 12.5 to
20 cm H2O. The peak
rate during PCV (Fig 3)
was markedly decreased at 0 to 5 cm H2O PEEP
(p < 0.05; Table 2
), assuming a more normal waveform at
10 cm
H2O PEEP but continuing to nonsignificantly
increase as PEEP was increased from 12.5 to 20 cm
H2O. Again, both pressure and
waveforms
were consistent with typical gas ventilation with the application of
10 cm H2O PEEP.
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decreased from a maximum of
0.35 ± 0.10 s at 0 cm H2O PEEP to
0.09 ± 0.02 s at 20 cm H2O PEEP (p < 0.05).
Airways resistance was 26.8 ± 10.7 cm H2O/L/s
at 0 cm H2O PEEP and decreased to 5.6 ± 1.0 cm
H2O/L/s at 20 cm H2O PEEP
(p < 0.05). The difference between PPLAT and PEEP
continually decreased with each increment of PEEP from 20.6 ± 6.59
cm H2O at 0 cm H2O PEEP to
11.49 ± 3.66 cm H2O at 20 cm
H2O PEEP (p < 0.05). The PIP minus
PPLAT decreased dramatically from 0 cm
H2O PEEP (25.9 ± 14.0 cm
H2O) to 20 cm H2O PEEP
(3.0 ± 0.4 cm H2O), as did PIP minus PEEP
(46.5 ± 19.4 cm H2O to 14.1 ± 4.5 cm
H2O), pressure at peak
minus PEEP
(35.2 ± 13.5 cm H2O to 9.5 ± 2.7 cm
H2O), time to peak
(0.45 ± 0.10 s to
0.30 ± 0.08 s), and peak
(0.92 ± 0.21 L/s to
0.54 ± 0.09 L/s) (p < 0.05). The opposite change occurred with
time to peak pressure, increasing from 0 cm H2O
PEEP (0.29 ± 0.07 s) to 20 cm H2O PEEP
(0.56 ± 0.01 s) (p < 0.05). Peak expiratory
also
decreased from 0 cm H2O PEEP (0.53 ± 0.13 L/s)
to 20 cm H2O PEEP (0.40 ± 0.09 L/s)
(p < 0.05). Finally, as shown in Figure 6
, as PEEP increased, the
quasi-static compliance increased from 18.93 ± 4.77 to
31.57 ± 9.84 mL/cm H2O (p < 0.05). There
were no significant differences in any variables as PEEP was increased
from 12.5 to 20 cm H2O.
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decreased from 0.65 ± 0.23 s at 0 cm H2O PEEP
to 0.14 ± 0.07 s at 20 cm H2O PEEP
(p < 0.05). Peak
increased from 0.16 ± 0.04 to
0.62 ± 0.11 L/s as PEEP increased from 0 to 20 cm
H2O (p < 0.05). Pressure at peak
minus
PEEP decreased from 13.6 ± 5.2 to 8.6 ± 5.5 cm
H2O, and peak pressure minus PEEP decreased from
19.0 ± 8.2 to 15.3 ± 5.9 cm H2O as PEEP
increased from 0 to 20 cm H2O (p < 0.05).
Contrary to volume ventilation, peak expiratory
decreased
(p < 0.05) as PEEP was increased from 0 to 20 cm
H2O (0.31 ± 0.10 to 0.42 ± 0.14 L/s).
Finally, as shown in Figure 6 , as PEEP increased from 0 to 20 cm H2O the
quasi-static compliance increased (9.61 ± 3.21 to 26.85 ± 9.54
mL/cm H2O) (p < 0.05). There were no
significant differences in any variables as PEEP was increased from
12.5 to 20.0 cm H2O.
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| Discussion |
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10 cm
H2O is needed to normalize airway pressure,
, and volume waveforms; (3) the PEEP level equivalent to the LIP
during PLV can be grossly estimated from the changes in airway
pressure,
, and volume waveforms; (4) with both volume- and
pressure-targeted ventilation, no measured variables significantly
changed at PEEP > 12.5 cm H2O; and (5) the mean
LIP (12.6 ± 1.1 cm H2O) was approximately
equivalent to the PEEP level (12.5 cm H2O) where
no additional significant changes in measured variables occurred.
Effects of PEEP
It has been demonstrated by numerous groups that in the gas-filled
lung of the ARDS patient, setting PEEP above the LIP of the P-V curve
of the total respiratory system prevents lung derecruitment and
improves oxygenation and lung mechanics.12
13
The partial
filling of the ARDS lung with PFC has been shown to have similar
effects.1
2
3
PLV demonstrates a dose-dependent improvement
in oxygenation and a reduction in shunt fraction.14
Recently, we demonstrated that the application of PEEP 1 cm
H2O above the LIP of the P-V curve in the lung
partially filled with PFC further increases oxygenation, reduces
physiologic dead space ventilation, and improves total respiratory
system compliance when compared with 5 cm H2O
PEEP.11
Similar data has been recorded by Kaisers
et al15
when 3.8, 7.6, and 11.4 cm
H2O PEEP were applied to a lung partially filled
with PFC. The mechanism for this improvement with PEEP is unclear but
may be a result of (1) the maintenance of PFC in the lung periphery at
end exhalation reducing impedance to gas ventilation, and (2) the
stabilization of the nondependent lung, preventing collapse.
Reduced Impedance: Perflubron has a density of 1.92
g/mL. This is coupled with the fact that at 0 cm H2O PEEP,
PFC resides not just in the lung periphery but in nondistendable
central airways, causing a high impedance to ventilation. At 0 cm
H2O PEEP, the impedance to gas delivery results in
distortion of the pressure and
waveform (Figs 2
, 3)
. During
pressure ventilation, the pressure target is rapidly met with minimal
delivery resulting in very small VT delivery.
Because of the high impedance, the pressure target is exceeded in early
inspiration. The ventilator cannot adjust
delivery rapidly
enough to prevent overshooting the set pressure target. With
volume-targeted ventilation, dramatic increases in peak airway pressure
(as compared with PEEP at LIP) are initially observed. The high PIP is
necessary to ensure that the
/VT targets are met. As
observed in Figure 4
and noted in Figure 2
, the time to 75% of peak
with 0 cm H2O PEEP is markedly increased over that
at
7.5 cm H2O PEEP, and the actual peak
is
higher than the set peak
(Table 1)
. The high impedance of the
PFC prevents the ventilator from achieving gas delivery in the
early phase of inspiration. As a result,
must increase above
the set level as the ventilator attempts to overcome the impedance of
the PFC and complete the VT delivery in the allocated time.
As noted in Table 1
, VT was constant during volume
ventilation regardless of the PEEP setting.
Nondependent Lung: In the gas-filled lung, while the animal is
in the supine position both perfusion and ventilation predominate in
the dependent regions. As recently demonstrated by Quintel et
al,16
with PLV, the majority of the VT goes to
the nondependent lung. In addition, a number of studies have shown that
in the lung partially filled with PFC to functional residual capacity
(FRC), there is a shifting of both intravascular and extravascular
fluid from the dependent to the nondependent lung.17
18
This shift in intrapulmonary fluid volume reverses the alveolar
inflation gradient. That is, in the lung partially filled with PFC the
nondependent region acts like the dependent region in the gas-filled
lung. In this setting, the alteration in the alveolar inflation
gradient favors instability and collapse of the nondependent lung. PEEP
stabilizes the nondependent lung, improving oxygenation. As would be
expected, the more the lung is filled with PFC, the greater is
the tendency for nondependent instability and the greater is the effect
of the addition of PEEP on oxygenation and lung
mechanics.11
Although other positions were not studied,
one would expect a similar situation to occur regardless of position.
That is, ventilation during PLV would always distribute to the
nondependent lung since the PFB would distribute to gravity.
LIP
After filling the lung with PFC, the LIP was measured at
12.6 ± 1.1 cm H2O. From the evaluation of the
changes in airway pressure and
waveforms, only nonsignificant
changes in all variables occurred with the application of a PEEP of
> 12.5 cm H2O. Visual observation of the airway
pressure and
waveforms in all animals showed the establishment
of waveforms equivalent to gas ventilation with PEEP set at
10 cm
H2O. Previously, we have measured the LIP on 34
(healthy and injured) sheep whose lungs were filled to FRC with
PFC.9
10
11
18
In all of these animals the LIP was between
10 and 15 cm H2O, averaging 11.9 ± 3.6 cm
H2O. This is in the same range (
10 cm
H2O) for which airway pressure and
curves
"normalized." These data imply that the minimal PEEP level during
PLV with an FRC fill should be that PEEP associated with normalization
of the airway pressure and
waveforms during both pressure- and
volume-targeted ventilation, but always
10 cm
H2O. Since the actual measurement of a P-V curve
is difficult and since all of our data point to a need for a PEEP of
about 12.5 cm H2O during PLV, we would recommend
that the initial setting of PEEP during PLV be at this level. The
assessment of pressure, volume, and
waveforms, and of
oxygenation above and below this level, should then be performed to
determine the final PEEP setting.
Pressure Ventilation
Of primary concern during pressure ventilation at low PEEP (< 10
cm H2O) was the low VT delivered.
This is a result of the limited driving pressure during pressure
ventilation (equal to the set pressure control level). With high
impedance, regardless of the cause, VT decreases, and the
application of PEEP more than or equal to the LIP reduces impedance in
the lung partially filled with PFC, which maximizes VT
delivery.18
Volume Ventilation
VT delivery was maintained during volume ventilation
regardless of the PEEP level but at a cost of markedly elevated peak
airway pressure. Since the PPLAT during low levels of PEEP
was not excessive, it is unlikely that this high peak pressure induced
lung injury.9
However, the use of low vs high PEEP with
the same VT reduces oxygenation.11
15
18
Increasing VT has been shown to improve oxygenation at low
PEEP, but it also increases PPLAT8
and the
risk of induced lung injury.9
10
Compliance
Increasing PEEP from 0 to
10 cm H2O in
both pressure and volume ventilation resulted in significantly
increased compliance. This corresponded to a continual decrease in the
difference between PPLAT and PEEP during volume ventilation
and the continual increase in VT in pressure ventilation.
Beyond 10 cm H2O, only minor nonsignificant
changes in compliance, PIP, and VT occurred. We do not
fully understand why. However, it may be primarily a result of
inadequate time for either end-inspiratory or end-expiratory
equilibration. As indicated, we measured quasi-static compliance.
During volume ventilation, the end-inspiratory hold period was 0.7
s, and during pressure ventilation it was < 0.2 s. As a result, each
compliance measurement may have underestimated actual compliance
because of the failure to reach static conditions. In fact, compliance
was always lower with PCV than with VCV (Fig 6)
. The application of
high levels of PEEP may have reduced the equilibration time and may
have resulted in a more accurate calculation of compliance especially
at PEEP levels of
10 cm H2O.
Limitations of the Study
There are several limitations of this study. As indicated above,
the methodology used to calculate compliance may have underestimated
compliance at all PEEP levels. No gas exchange or hemodynamic data are
presented. However, our previous data do indicate a greater
PaO2 and lower
PCO2 when PEEP is 1 cm
H2O above the LIP11
compared with
PEEP at 5 cm H2O, and they indicate no greater
hemodynamic compromise than when PEEP was set at 5 cm
H2O.11
18
Other studies also have
observed improved oxygenation without hemodynamic compromise at PEEP
levels of 11.4 cm H2O when compared with a lower
PEEP setting.15
Finally, this study was performed in a
noninjured sheep model, which may not represent the actual changes that
occur in patients with ARDS.
| Conclusion |
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, and volume waveforms. The use of low-level
PEEP results in a marked decrease in VT in PCV and a marked
increase in airway pressure in VCV. Observation of the airway pressure
and
waveforms in either pressure or volume ventilation are
useful in grossly identifying the LIP on the P-V curve of the lung
partially filled with PFC. In this animal model, normalization of the
airway pressure and
waveform was always associated with a PEEP
level of
10 cm H2O.
| Footnotes |
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= flow; VCV = volume
control ventilation; VT = tidal volume; Supported in part by Alliance Pharmaceutical Corp. Dr. Fujino was supported by a grant from the Japanese Government. Dr. Goddon was supported by a grant from the Deutsche Forschungsgemeinschaft (GO 855/11).
Received for publication April 7, 1999. Accepted for publication August 10, 1999.
| References |
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