Vol. 90, Issue 4, 1365-1372, April 2001
Role of ventilation strategy on perfluorochemical evaporation
from the lungs
Mei-Jy
Jeng1,2,5,
Daniele
Trevisanuto3,
Carla
M.
Weis4,
William W.
Fox4,
Aaron B.
Cullen5,
Marla R.
Wolfson5, and
Thomas H.
Shaffer5
1 Institute of Clinical Medicine, National Yang-Ming
University School of Medicine, Taipei; 2 Department of
Pediatrics, Children's Medical Center, Veterans General
Hospital-Taipei, Taipei 11217, Taiwan, Republic of China;
3 Department of Pediatrics, Padua University, Padua 35158, Italy; 4 Department of Neonatology, Children's
Hospital of Philadelphia, University of Pennsylvania School of
Medicine; and 5 Departments of Physiology and Pediatrics,
Temple University School of Medicine, Philadelphia,
Pennsylvania 19140
 |
ABSTRACT |
To study the effect of ventilation strategy on
perfluorochemical (PFC) elimination profile (evaporative loss profile;
EL), 6 ml/kg of perflubron were instilled into anesthetized
normal rabbits. The strategy was to maintain minute ventilation
(
E, in ml/min) in three groups:
EL (low-range E,
208 ± 2), EM (midrange
E, 250 ± 9), and
EH (high-range E,
293 ± 1) over 4 h. In three other groups,
respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with
a constant E and adjusted tidal volume. PFC content
in the expired gas was measured, and EL was calculated.
There was a significant E- and time-dependent effect
on EL. Initially, percent PFC saturation and loss rate decreased in the EH > EM > EL groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that
EH < EM < EL at 4 h. For the groups at
constant E, there was a significant time effect on
EL but no RR effect. In conclusion, EL profile
is dependent on E with little effect of the RR-tidal volume combination. Thus measurement of EL and
E should be considered for the replacement dosing
schemes during partial liquid ventilation.
partial liquid ventilation; minute ventilation; elimination; rabbit
| |
INTRODUCTION |
PARTIAL LIQUID
VENTILATION (PLV) with perfluorochemical (PFC) has been shown
effective in treating a variety of respiratory diseases and is
currently in Phase II/III clinical trials with perflubron. Numerous
investigators have reported improved gas exchange, lung mechanics, and
survival, as well as a reduction in the degree of lung injury and
inflammatory infiltrates in animals and humans on PLV compared with gas
ventilation (2, 4, 12, 20, 24, 25, 33, 38, 39, 42). A
stable PFC volume in the lungs is desirable to optimize the beneficial
effects of PLV (29). However, the best way to maintain the
PFC liquid level in the lungs is still under investigation. Evaporation
of PFC is related to a number of factors that make PFC replacement
dosing unclear. Previous investigations have shown that the elimination of PFC from the lungs is associated with the air-PFC liquid interface and influenced by the PFC physical properties, the dosing volume and
frequency of dosing, body position, lung volume (possibly in
combination with positive end expiratory pressure), and the effect of
lung injury in combination with extracorporeal membrane oxygenation
(16, 17, 29, 37, 41, 43). However, there is no available
information on ventilation strategy and its effects on elimination of
PFC during PLV.
With regard to ventilation strategy, we hypothesized that the PFC
elimination profile (EL; percent PFC saturation and PFC loss rate) is dependent on minute ventilation (E)
and the respiratory rate (RR)-tidal volume (VT)
combination. Therefore, the present study was designed to test the
effects of E and RR-VT combination on
the PFC elimination from the respiratory system. In addition, a
secondary endpoint of the study was to evaluate the effect of PFC
elimination on pulmonary gas exchange and function.
| |
METHODS |
All animals were managed according to the NIH regulations
Guide for the Care and Use of Laboratory Animals. In
addition, all procedures were approved by the Institutional Animal Care
Use Committee of Temple University.
Animal Preparation
Thirty-six New Zealand White juvenile rabbits (weight 2.2 ± 0.1 kg) with normal lungs were anesthetized with an intramuscular injection of a mixture of ketamine (23 mg/kg), acepromazine (0.58 mg/kg), and xylazine (0.8 mg/kg). This particular animal model was
chosen on the basis of our previous experience with the model, the
suitability of the model as it applies to neonatal and pediatric medicine, and the history of this preparation for PLV studies (1,
16, 17, 21, 37-41). The skin and soft tissues were anesthetized with 0.5% lidocaine HCl (4 mg/kg) and instrumented with
tracheostomy placement of a 3-mm-ID endotracheal tube (Hi-Lo Jet Tube,
Mallincrodkt, Saint Louis, MO). Catheters were placed in a jugular vein
and carotid artery. Conventional gas ventilation with a time-cycled,
pressure-limited ventilator (BP-200, Bear Medical Systems, Riverside,
CA) was established to maintain physiological cardiopulmonary
condition. Subsequent anesthesia was maintained with intravenous
injection of the above anesthesia drug (one-tenth of initial anesthesia
dose) hourly. Muscle relaxation was induced by intravenous
administration of pancuronium bromide (0.1 mg/kg) and maintained with
continuous infusion (0.15 mg · kg
1 · h1) throughout
the experiments. Maintenance fluid was provided by a continuous
infusion of 5% dextrose at a rate of 5 mg · kg1 · h1. Arterial
blood pressure was monitored by attaching the arterial catheter to a
standard pressure transducer, connected to a neonatal monitor
(Athena/Neonatal 9040, S & W Medico Teknik, Albertslund, Denmark).
Electrocardiogram electrodes and a rectal temperature probe were
inserted for monitoring. The animal's rectal temperature was
maintained within 37-38°C.
Experimental Protocol
E protocol.
Nineteen animals were randomly assigned to one of three groups to study
the effect of E on the PFC elimination profile. Constant E was maintained in each group throughout
the experiment: low-range E target
(EL = 205-215), midrange
E target (EM = 245-255), and high-range E target
(EH = 285-395
ml · kg1 · min1), which
were determined by our pilot study to keep the arterial partial
pressure of CO2 (PaCO2) in a physiological
range. The E was maintained constant in each group
by monitoring VT every 15-30 min using
pneumotachography (PEDS-LAB, MAS, Hatfield, PA) and appropriately
adjusting ventilator peak inflation pressure. In addition, several
healthy rabbits ventilated without PFC were also studied, as described
by Tutuncu et al. (40), to confirm cardiopulmonary
stability of the animal preparation over time.
Ventilation strategy protocol.
Seventeen animals were randomly assigned to one of three additional
groups to study the effect of varying RR and VT on PFC elimination from the respiratory system. RR (breaths/min) was controlled at RR20 = 20, RR30 = 30, and RR50 = 50, and VT was corrected by
adjusting peak inflation pressure and positive end-expiratory pressure
to maintain E (E = 275-290
ml · min1 · kg1) and mean
airway pressure (7-8 cmH2O) in a constant range. Mean airway pressure was maintained constant in an attempt to regulate end-expiratory lung volume, which is associated with the air-PFC liquid interface.
In all study groups, other ventilation profiles were maintained
constant: inspiratory time 0.3 s, positive end-expiratory pressure
5-6 cmH2O, inspired O2 fraction = 1.0. Baseline expired gas and arterial blood samples were obtained
followed by sequential measurements every 60 min. Pulmonary mechanics
(PEDS-LAB, MAS, Hatfield, PA) were measured every 60 min as previously
described (3). Animal position (supine), airway
temperature (35°C), and humidity (100%) were kept constant
throughout the experiment. Perflubron (6 ml/kg; LiquiVent, Alliance
Pharmaceutical, San Diego, CA) was instilled into the lungs via the
side port of the endotracheal tube for 5-10 min. During
instillation, the animal was repositioned to optimize PFC distribution
by using four equal increments of the total dose, with Trendelenberg,
reverse Trendelenberg, and left and right lateral decubitus positions.
Expired gas samples were manually collected over 30 s (using a
stopcock on a side port of the endotracheal tube into a 50-ml rebreathing bag) at 15 min after PFC instillation and then every 30 min
(16, 17, 21, 29, 41). In each sample of expired gas, the
percent PFC saturation and expired CO2 tension
(NOVA blood gas instrument) at 37°C were measured by using a
modification of a previously described thermal detector device
(29). The percent PFC saturation values were corrected for
the CO2 content and water vapor in the expired gas samples
as previously described (29).
All of the experiments were continued for 4 h. Arterial partial
pressure of O2 (PaO2) was maintained >100
mmHg and pH was maintained in a physiological range. At the end of the
experiments, the animals were euthanized with 15% potassium chloride.
Calculations
The EL was established by determining the following
parameters, based on previous studies (21, 29, 41)
|
(1)
|
|
(2)
|
|
(3)
|
Data Analysis
One-way analysis of variance (ANOVA) was used to compare basic
physiological data as a function of time. Two-way ANOVA and post hoc
analysis with Student-Newman-Keuls correction for multiple comparisons
were performed to compare EL and other parameters as a
function of time and groups. One-way ANOVA and post hoc analysis with
Student-Newman-Keuls correction were performed to compare the values of
EL and other parameters at each time point. Significance was accepted at the P < 0.05 level.
| |
RESULTS |
E Study
As shown in Table 1 (mean ± SE), body weight did not differ significantly across groups.
E was maintained constant in three significantly
(P < 0.01) different ranges
(EH = 293 ± 1 > MHM = 250 ± 9 > EL = 208 ± 2 ml · kg1 · min1). Figure
1 shows the percent PFC saturations and
the loss rate of PFC over time for each group. As shown, the
relationship is significantly (P < 0.05) dependent on
E and time. After the initial instillation, the
expired gas in all groups was saturated with approximately the same
amount of PFC (50% saturation). The percent PFC saturation of expired
gas declined over time for all groups; however, the expired gas
remained relatively saturated with PFC for a longer time at lower
levels of E. Initially, the loss rate of the groups
with higher E was greater
(EH > EM > EL) because of the
E, but, by 3 h, the lower percent PFC
saturation resulted in a loss rate such that
EH < EM < EL at 4 h.
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 1.
Top: percent perfluorochemical (PFC)
saturation (%PFC saturation) in expired gas samples for each group
with different minute ventilation (E) as a function
of time after instillation. There was a significant difference (P
< 0.05) in E-time interaction among groups.
All 3 groups changed significantly (P < 0.05) over time
after instillation. *P < 0.05 vs.
EH group by post hoc analysis.
Bottom: PFC evaporative loss rate for each group as a
function of time after instillation. All three groups changed
significantly (P < 0.05) over time after instillation.
*P < 0.05 vs. EH
group by post hoc analysis. All data are presented as means ± SE.
EL, EM,
and EH, low, mid, and high
E groups, respectively.
|
|
The relationship of residual PFC in the lung and the PFC loss as a
percentage of initial dose over time for each group is shown in Fig.
2. There were lower amounts of residual
PFC in the lungs and a higher loss (percentage of initial PFC dose) in
the groups with higher E during the first 3 h.
Table 2 (means ± SE) demonstrates
how the redosing interval is dependent on the E such
that replacement doses are needed sooner when the E is higher. For example, it takes 20 min longer for the
EL group to lose 20% of the initial
dose compared with the EH group.
View larger version (18K):
[in this window]
[in a new window]
|
Fig. 2.
PFC loss as a percentage of initial dose (top)
and residual PFC in the lung (bottom) for each group with
different E as a function of time after
instillation. There was a significant difference (P < 0.05)
in E-time interaction among groups. All 3 groups
changed significantly (P < 0.05) over time after
administration in both PFC loss and residual PFC. *P < 0.05 vs. EH group by post hoc analysis. All
data are presented as means ± SE.
|
|
Table 3 illustrates the cardiopulmonary
profiles of animals in the E groups. As a function
of time and group, there were significant changes in
PaO2 and Cdyn over time (P < 0.05).
However, there are significant changes in Cdyn% as a function of time
only and in PaCO2 as a function of group only (P
< 0.05).
Ventilation Strategy Study
As shown in Table 1, the body weight and E did
not differ significantly among groups. By design, different breathing
rates were set for each group, and thus VT was adjusted to
maintain a similar E = 283 ± 4 SE
ml · kg1 · min1. Figure
3 demonstrates that percent PFC
saturation and PFC loss rate were each significantly (P < 0.05) dependent on time, but there was no effect of RR. As shown, Fig.
4 demonstrates that the PFC loss and the
residual amount of PFC in the lung are each significantly (P
< 0.01) correlated with time, but there was no significant
difference with respect to RR.
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 3.
PFC saturation in expired gas samples (top)
and PFC evaporative loss rate (bottom) for each group with
different ventilation strategy as a function of time after
administration. All 3 groups changed significantly (P < 0.05) over time after instillation. However, there was no significant
difference among groups. All data are presented as means ± SE.
RR, respiratory rate; RR20, RR30, and
RR50, 20, 30, and 50 breaths/min groups, respectively.
|
|
View larger version (17K):
[in this window]
[in a new window]
|
Fig. 4.
PFC loss as a % of initial dose (top) and
residual PFC in the lungs (bottom) for each group with
different ventilation strategy as a function of time after
instillation. All 3 groups changed significantly (P < 0.05)
over time after instillation. However, there was no significant
difference among groups. All data are presented as means ± SE.
|
|
Table 4 illustrates the cardiopulmonary
profiles in the ventilation strategy study. As a function of time and
group, there is a significant change in Cdyn over time (P < 0.05). However, there are significant changes in Cdyn% and
PaO2 as a function of time only and in
PaCO2 as a function of group only (P < 0.05).
Figure 5 illustrates the relationship
between residual PFC and both PaO2 and Cdyn% in all
study groups (E and ventilation strategy groups).
Although parametric in time, these data represent time points from 15 min to 4 h after PFC instillation. As shown in Fig. 5
(top), there was a significant (P < 0.001)
positive correlation between the amount of residual PFC and the
PaO2 (r = 0.55). Likewise, as shown in
Fig. 5 (bottom), there was a significant (P < 0.001) positive correlation between the amount of residual PFC and
Cdyn% (r = 0.87). These data indicate a physiological correlation between oxygenation, lung mechanics, and residual perflubron in the lungs; thus, as residual perflubron is diminished as
a result of evaporative loss, there is a deterioration in both oxygenation and lung compliance.
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 5.
Correlation between arterial partial pressure of
O2 (PaO2) and residual PFC in the lungs
with a regression line (top). PaO2 = 256.2 + (25.7 × residual PFC), r = 0.55, P < 0.001. Correlation between dynamic compliance as
a percentage of baseline (Cdyn%) and residual PFC in the lung with a
regression line (bottom). The Cdyn% (% of baseline) = 39.3 + (11.0 × residual PFC), r = 0.87, P < 0.001. All data are presented as means ± SE.
|
|
| |
DISCUSSION |
The data presented herein demonstrate that when
E is increased during PLV, the evaporative loss of
PFC is increased. This information has significant implications with
respect to subsequent redosing during the clinical application of PLV.
Higher evaporative loss from the lungs in subjects treated with higher
E indicates it is necessary to replace PFC sooner
than those with lower E. As noted herein, to
maintain 80% of the initial dose in the lungs, the
EH group would require dosing 20 min
more frequently than the EL group. In
addition, as noted in Fig. 5, there are graded physiological
consequences in oxygenation and pulmonary compliance associated with
evaporative loss and no replacement dosing. Furthermore, during PLV
with the same E, it was shown that all components of
EL are dependent on time after instillation and not
ventilation strategy (high RR vs. low RR). Thus ventilation strategy
has little impact on PFC redosing schedule during PLV.
The physiochemical properties of PFC liquid have been studied by
previous investigators (7, 18, 22, 27, 44). The vapor
pressure of breathable PFC liquids ranges from 0.2-400 mmHg at a
temperature of 37°C, so the rate of evaporative loss from the
respiratory system is vapor pressure dependent (29). Also, PFC volatilization from the lungs is the major route of elimination from the body, because PFC is not metabolized in the body (31, 43). In addition to vapor pressure, several other factors
influence the elimination of PFC from the lungs, including the
physicochemical properties of PFC and physiological factors of animals
or humans (43).
As previously reported, it appears that maintaining the amount of PFC
liquid in damaged lungs prevents time-dependent changes in gas exchange
and pulmonary function during PLV (1, 6, 8, 9, 11-14,
23-25, 38, 39, 42, 44). Therefore, it is valuable to have a
continuous assessment of the amount of PFC in the lung to maintain the
physiological effectiveness of PLV. Several radiological studies have
also confirmed the evaporation and redistribution processes in animals
and humans after administration of various amounts of PFC into the
lungs (8, 10, 17, 34, 36, 45). On the basis of these
findings, investigators focused on the design of methods for monitoring
the elimination of PFC from the lungs (15, 21, 29). Using
the thermal detector method, Miller et al. (17) reported
that the elimination rate after multiple doses of PFC would be
significantly higher than that after a single dose. Likewise, Weis et
al. (41) reported that the elimination of PFC was
dependent on the initial dose and the time after instillation.
Preliminary data indicate that repositioning during PLV modulates PFC
elimination from the lungs and that position (supine vs. prone) during
PLV results in a different loss rate (5, 17, 29). To
prevent PFC elimination during PLV, several ventilator circuit designs
for PFC dose maintenance are currently under investigation (19,
28).
In the present study, the primary focus was on E and
ventilation strategy and subsequent effects on perflubron elimination during 4 h of PLV. In addition, the physiological consequences associated with perflubron evaporation were correlated with
E and ventilation strategy. Numerous animal and
clinical studies have reported the need to redose perflubron during
short-term and long-term PLV; however, none of these studies was able
to correlate the need for redosing with the actual evaporative loss of
perflubron (9, 11-13, 23, 26, 42). The results
presented herein show that, with regard to ventilator management,
E is a major factor that influences the elimination
of perflubron from the lungs. Thus, whenever E is
adjusted during PLV as a result of ventilator management and clinical
care, it is necessary to consider the influence of E
changes on perflubron elimination and to adjust the redosing schedule
appropriately. As noted by Weis et al. (41), the need for
redosing is potentiated by initial dose requirements; that is, lower
initial doses (6 ml/kg) require more frequent dosing than larger
initial doses (18 ml/kg). It is also noteworthy that in the present
study it was found that, as long as E was maintained
constant, alterations in RR from 20 to 50 breaths/min had little effect
on PFC loss profile.
The issue of an "optimum initial PFC dose" is still under
investigation, although doses from 25 to 100% of FRC have been studied with varied success (6, 14, 26, 32, 42). In the present experiment, we initially administered 6 ml/kg perflubron into the
lungs, ~1/3 the normal FRC volume of a juvenile rabbit (17, 41). We based this initial dose on previous studies (17,
41) as well as on the low dose protocol for the current phase
III, adult clinical trial for PLV (personal communication, Dr. Mark Wedel, Alliance Pharmaceutical). In addition, it has been reported that
this volume of perflubron is sufficient to coat the lung because of a
conformational change from a droplet to a film during inflation
(35).
Partial liquid ventilation with PFC liquid has been reported to be
effective in treating experimental respiratory failure (12,
44). Success has been associated with the high solubility of
respiratory gases in the PFC liquid that support gas exchange. Furthermore, several investigators also noticed that lung compliance could improve due to the recruitment of alveoli and reducing the surface tension in damaged lungs (23, 35, 38, 39, 41, 42).
In contrast to the injured lung, numerous studies have shown that
residual PFC liquid in a healthy lung does not improve pulmonary
mechanics or gas exchange. In addition, it has been shown that the gas
exchange response to residual PFC liquid in the lungs is inversely
related to lung condition (30). Furthermore, it has been
shown that during prolonged PLV (without replacement dosing), there is
a deterioration of lung mechanics, gas exchange, and histology, which
suggested that atelectasis does occur during return to conventional
mechanical ventilation. These findings have also been shown in the
short-term studies presented herein. It is noteworthy that
time-dependent deterioration in oxygenation and compliance were not
observed in our pilot studies of rabbits with healthy lungs without
PLV. In addition, to the degree that these studies were in agreement
with that of Tutuncu et al. (40), time-dependent
deterioration in cardiopulmonary function can be excluded, with reason,
as a possible covariant in the relationship between oxygenation and
compliance with residual PFC volume.
The mechanism for alterations in gas exchange and lung mechanics can be
explained as illustrated in Fig. 6. As
shown, when the lungs are initially instilled with PFC (depending on
the initial dose), most of the alveoli are recruited. Thus the lung is
divided into three compartments: 1) gas filled with a PFC
film lining (nondependent); 2) partially gas filled with a
PFC film lining and partially PFC liquid filled (midlung region); and
3) PFC liquid filled (dependent). As PFC liquid evaporates
and the animals are still paralyzed, the alveoli with PFC are more
likely to remain expanded. Nondependent and midlung regions demonstrate
the highest degree of clearing, whereas the dependent regions remain
relatively liquid filled (17). Thus derecruitment of
alveoli secondary to PFC evaporation is probably associated with the
observed deterioration in oxygenation and compliance (Fig. 5). Although
the present study is not supported with histopathological evidence,
previously we have shown that nonuniform PFC distribution and
histopathological correlates during PLV of the respiratory distress
syndrome lung (44). Therefore, to prevent unnecessary
compromise in oxygenation and lung mechanics, as shown herein, accurate
replacement of evaporated PFC is crucial to maintain optimum treatment
with PLV, especially when the E is changed.
View larger version (13K):
[in this window]
[in a new window]
|
Fig. 6.
Illustration of PFC evaporation from the healthy lung. Black
regions represent PFC liquid in the alveoli and the PFC film lining on
the alveolar walls. I: healthy alveoli in gas ventilation.
II: partial liquid ventilation (PLV), after administration
of PFC to the lungs; most alveoli in the dependent (D) region are
completely PFC filled, whereas those in the nondependent (ND) regions
are gas-filled and have a PFC film lining. Alveoli in the midlung
region are partially gas and PFC liquid-filled. III: PLV
after 2 h; some PFC has evaporated, resulting in alveolar
collapse. IV: PLV after 4 h; more PFC has evaporated,
resulting in derecruitment and further collapse of alveoli with only a
few alveoli lined with PFC in the nondependent region.
|
|
In conclusion, for the presented juvenile animal model, it was found
that the evaporative loss profile is dependent on E with little effect of the RR-VT combination. Thus
assessment of PFC evaporative loss and E should be
considered for the replacement dosing schemes during PLV. Finally, the
present study was conducted in healthy juvenile animals. These data
suggest that further studies of injured, larger, and human lungs in a
clinical setting are warranted to evaluate the effect of ventilation
strategy on PFC elimination.
| |
ACKNOWLEDGEMENTS |
We gratefully acknowledge the expert technical assistance of Rita
Garbarino and Rachel Laudadio.
| |
FOOTNOTES |
This work was performed at Temple University School of Medicine and was
supported in part by Alliance Pharmaceutical.
Address for reprint requests and other correspondence: M.-J.
Jeng, Dept. of Pediatrics, Children's Medical Center, Veterans General
Hospital-Taipei, No. 210, Section 2, Shih-Pei Road, Taipei 11217, Taiwan, ROC (E-mail: mjjeng{at}yahoo.com or
tshaffer{at}astro.ocis.temple.edu).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 19 September 2000; accepted in final form 26 October 2000.
| |
REFERENCES |
1.
Al-Rahmani, A,
Awad K,
Miller TF,
Wolfson MR,
and
Shaffer TH.
Effects of partial liquid ventilation with perfluorodecalin in the juvenile rabbit lung after saline injury.
Crit Care Med
28:
1459-1464,
2000[Web of Science][Medline].
2.
Bartlett, R,
Croce M,
Hirschl RB,
Gore D,
Wiedemann H,
Davis K,
and
Zwischenberger J.
A phase II randomized, controlled trial of partial liquid ventilation (PLV) in adult patients with acute hypoxemic respiratory failure (AHRF) (Abstract).
Crit Care Med
25:
A135,
1997.
3.
Bhutani, VK,
Sivieri EM,
Abbasi S,
and
Shaffer TH.
Evaluation of neonatal pulmonary mechanics and energetics: a two factor least mean square analysis.
Pediatr Pulmonol
4:
150-158,
1988[Web of Science][Medline].
4.
Colton, DM,
Hirschl RB,
Johnson KJ,
Till GO,
Dean SB,
and
Barlett RH.
Neutrophil infiltration is reduced during partial perfluorocarbon liquid ventilation in the setting of lung injury.
Surg Forum
1055:
668-670,
1994.
5.
Doctor, A,
Al-Khadra E,
Watson K,
Thompson J,
and
Arnold J.
Perfluorocarbon (PFC) vapor loss during high frequency ventilation: effect of intrapulmonary PFC distribution and volume (Abstract).
Am J Respir Crit Care Med
161:
A46,
2000.
6.
Fuhrman, BP,
Paczan PR,
and
DeFrancisis M.
Perfluorocarbon-associated gas exchange.
Crit Care Med
19:
712-722,
1991[Web of Science][Medline].
7.
Gabriel, JL,
Miller TF,
Wolfson MR,
and
Shaffer TH.
Quantitative structure-activity relationship of perfluorinated hetero-hydrocarbons as potential respiratory media: application to oxygen solubility, log P, viscosity, vapor pressure and density.
ASAIO J
42:
968-973,
1996[Web of Science][Medline].
8.
Greenspan, JS,
Fox WW,
Rubenstein SD,
Wolfson MR,
Spinner SS,
and
Shaffer TH.
Partial liquid ventilation in critically ill infants receiving extracorporeal life support.
Pediatrics
99:
E2,
1997.
9.
Greenspan, JS,
Wolfson MR,
Rubenstein SD,
and
Shaffer TH.
Liquid ventilation of human preterm neonates.
J Pediatr
117:
106-111,
1990[Web of Science][Medline].
10.
Gross, GW,
Greenspan JS,
Fox WW,
Rubenstein SD,
Wolfson MR,
and
Shaffer TH.
Use of liquid ventilation with perflubron during extracorporeal membrane oxygenation: chest radiographic appearance.
Radiology
194:
717-720,
1995[Abstract/Free Full Text].
11.
Hirschl, RB,
Pranikoff T,
Gauger P,
Schreiner RJ,
Decert R,
and
Bartlett RH.
Liquid ventilation in adults, children and neonates.
Lancet
346:
1201-1202,
1995[Web of Science][Medline].
12.
Hirschl, RB,
Tooley R,
Parent A,
Johnson K,
and
Barlett RH.
Improvement of gas exchange, pulmonary function, and lung injury with partial liquid ventilation: a study model in a setting of severe respiratory failure.
Chest
108:
500-508,
1995[Abstract/Free Full Text].
13.
Leach, CL,
Greenspan JS,
Rubenstein SD,
Shaffer TH,
Wolfson MR,
Jackson JC,
DeLemos R,
Fuhrman BP,
and
the LiquiVent Study Group
Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome.
N Engl J Med
335:
761-767,
1996[Abstract/Free Full Text].
14.
Leach, CL,
Holm B,
Morin FC, III,
Fuhrman BP,
Papo MC,
Steinhorn D,
and
Hernan LJ.
Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.
J Pediatr
126:
412-420,
1995[Web of Science][Medline].
15.
Mazzoni, M,
Nugent L,
Klein D,
Hoffman J,
Sekins KM,
and
Flaim SF.
Dose monitoring in partial liquid ventilation by infrared measurement of expired perfluorochemicals.
Biomed Instrum Technol
33:
356-364,
1999[Medline].
16.
Miller, TF,
Greenspan JS,
Fox WW,
Foust R,
Philips C,
Wolfson MR,
and
Shaffer TH.
Combined ventilation, and partial liquid ventilation (PLV) in human neonates: LiquiVent perfluorochemical (PFC) elimination (Abstract).
Pediatr Res
39:
234A,
1996.
17.
Miller, TF,
Milestone BN,
Stern RG,
Shaffer TH,
and
Wolfson MR.
Effect of single versus multiple dosing on perfluorochemical distribution and elimination profile during partial liquid ventilation.
Pediatr Pulmonol
27:
410-418,
1999[Web of Science][Medline].
18.
Moore, RE,
and
Clark LC, Jr.
Chemistry of fluorocarbons in biomedical use.
Int Anesthesiol Clin
23:
11-24,
1985[Web of Science][Medline].
19.
Nugent, LJ,
Mazzoni MC,
Flaim SF,
Hoffman JK,
and
Sekins KM.
Dose maintenance for partial liquid ventilation: passive heat-and-moisture exchangers.
Biomed Instrum Technol
33:
365-372,
1999[Medline].
20.
Papo, MC,
Paczan PR,
Fuhrman BP,
Steinhorn DM,
Hernan LJ,
Leach LJ,
Holm BA,
Fisher JE,
and
Kahn BA.
Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.
Crit Care Med
24:
466-474,
1996[Web of Science][Medline].
21.
Philips, CM,
Weis C,
Fox WW,
Wolfson MR,
and
Shaffer TH.
On line techniques for perfluorochemical vapor sampling and measurement.
Biomed Instrum Technol
33:
348-355,
1999[Medline].
22.
Reiss, JG.
Reassessment of criteria for the selection of perfluorochemicals for second-generation blood substitutes: analysis of structure/property relationships.
Artif Organs
8:
44-56,
1984[Web of Science][Medline].
23.
Richman, PS,
Wolfson MR,
and
Shaffer TH
Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.
Crit Care Med
21:
768-774,
1993[Web of Science][Medline].
24.
Rotta, AT,
Gunnarsson B,
Hernan LJ,
and
Steinhorn DM.
Partial liquid ventilation influences pulmonary histopathology in an animal model of acute lung injury.
J Crit Care
14:
84-92,
1999[Web of Science][Medline].
25.
Rotta, AT,
and
Steinhorn DM.
Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury.
Crit Care Med
26:
1707-1715,
1998[Web of Science][Medline].
26.
Salman, NH,
Fuhrman BP,
Steinhorn DM,
Papo MC,
Hernan LJ,
Leach CL,
and
Fischer JE.
Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilation.
Crit Care Med
24:
548-549,
1996[Web of Science][Medline].
27.
Sargent, JW,
and
Seffl RJ.
Properties of perfluoronated liquid.
Fed Proc
29:
1699-1703,
1970[Web of Science][Medline].
28.
Schrader, B,
Westenskow D,
Kofoed S,
Durst K,
Orr J,
Flanagan C,
Mazzoni M,
Hoffman J,
and
Sekins M.
A closed rebreathing system for dose maintenance during partial liquid ventilation.
Biomed Instrum Technol
33:
373-382,
1999[Medline].
29.
Shaffer, TH,
Foust R,
Wolfson MR,
and
Miller TF.
Analysis of perfluorochemical elimination from the respiratory system.
J Appl Physiol
83:
1033-1040,
1997[Abstract/Free Full Text].
30.
Shaffer, TH,
Tran N,
Bhutani VK,
and
Sivieri EM.
Cardiopulmonary function in very preterm lambs during liquid ventilation.
Pediatr Res
17:
680-684,
1983[Web of Science][Medline].
31.
Shaffer, TH,
Wolfson MR,
Greenspan JS,
Hoffman RE,
Davis SL,
and
Clark LC, Jr.
Liquid ventilation in premature lambs: uptake, biodistribution and elimination of perfluorodecalin liquid.
Reprod Fertil Dev
8:
409-416,
1996[Medline].
32.
Steinhorn, DM,
Leach CL,
Fuhrman BP,
and
Holm BA.
Partial liquid ventilation enhances surfactant phospholipid production.
Crit Care Med
24:
1252-1256,
1996[Web of Science][Medline].
33.
Steinhorn, DM,
Papo MC,
Rotta AT,
Aljada A,
Fuhrman BP,
and
Dandona P.
Liquid ventilation attenuates pulmonary oxidative damage.
J Crit Care
14:
20-28,
1999[Web of Science][Medline].
34.
Stern, RG,
Wolfson MR,
McGuckin JF,
Forge JA,
and
Shaffer TH.
High-resolution computed tomographic bronchiolography using perfluoroctylbromide (PFOB): an experimental model.
J Thorac Imaging
8:
300-304,
1993[Medline].
35.
Tarczy-Hornoch, P,
Hildebrandt J,
Standaert TA,
and
Jackson JC.
Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ.
J Appl Physiol
84:
1316-1322,
1998[Abstract/Free Full Text].
36.
Thomas, SR,
Clark LC, Jr,
Ackerman JL,
Pratt RG,
Hoffman RE,
Busse LJ,
Kinsey RA,
and
Samaratunga RC.
MR imaging of the lung using liquid perfluorocarbons.
J Comput Assist Tomogr
10:
1-9,
1986[Web of Science][Medline].
37.
Trevisanuto, D,
Jeng MJ,
Weis CM,
Fox WW,
Wolfson MR,
and
Shaffer TH.
Positive end-expiratory pressure (PEEP) modulates perfluorochemical (PFC) evaporation from the lungs (Abstract).
Pediatr Res
47:
436A,
2000.
38.
Tutuncu, AS,
Akpir K,
Mulder P,
Erdmann W,
and
Lachmann B.
Intratracheal perfluorocarbon administration as an aid in the ventilation management of respiratory distress syndrome.
Anesthesiology
79:
1083-1093,
1993[Web of Science][Medline].
39.
Tutuncu, AS,
Faithfull NS,
and
Lachmann B.
Intratracheal perfluorocarbon administration combined with mechanical ventilation in experimental respiratory distress syndrome: dose-dependent improvement of gas exchange.
Crit Care Med
21:
962-969,
1993[Web of Science][Medline].
40.
Tutuncu, AS,
Houmes RJ,
Bos JA,
Wollmer P,
and
Lachmann B.
Evaluation of lung function after perfluorocarbon administration in healthy animals.
Crit Care Med
24:
274-279,
1996[Web of Science][Medline].
41.
Weis, C,
Fox WW,
Philips CM,
Wolfson MR,
and
Shaffer TH.
Effect of initial dosing volume on elimination from the lungs (Abstract).
Pediatr Res
43:
302A,
1998.
42.
Wolfson, MR,
Greenspan JS,
Deoras KS,
Rubenstein SD,
and
Shaffer TH.
Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates.
J Appl Physiol
72:
1024-1031,
1992[Abstract/Free Full Text].
43.
Wolfson, MR,
Greenspan JS,
and
Shaffer TH.
Liquid-assisted ventilation: an alternative respiratory modality.
Pediatr Pulmonol
26:
42-63,
1998[Web of Science][Medline].
44.
Wolfson, MR,
Kechner NE,
Roache RF,
Dechadarevian JP,
Friss HE,
Rubenstein SD,
and
Shaffer TH.
Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency.
J Appl Physiol
84:
624-640,
1998[Abstract/Free Full Text].
45.
Wolfson, MR,
Stern RG,
Kechner N,
Sekins KM,
and
Shaffer TH.
Utility of a perfluorochemical liquid for pulmonary diagnostic imaging.
Artif Cells Blood Substit Immobil Biotechnol
22:
1409-1420,
1994[Web of Science][Medline].
J APPL PHYSIOL 90(4):1365-1372
8750-7587/01 $5.00
Copyright © 2001 the American Physiological Society
TOP
ABSTRACT
INTRODUCTION
