(Chest. 2001;120:1655-1662.)
© 2001
American College of Chest Physicians
Pulmonary and Extrapulmonary Effects of Increased Colloid Osmotic Pressure During Endotoxemia in Rats*
Maria T. Camacho, MD;
Balagangadhar R. Totapally, MD;
Dan Torbati, PhD and
Jack Wolfsdorf, MD, FCCP
*
From the Division of Critical Care Medicine, Miami Children’s Hospital, Miami, FL.
Correspondence to: Dan Torbati, PhD, Associate Professor and Research Director, Division of Critical Care Medicine, Miami Children’s Hospital, Miami, FL 33155-3009; e-mail: Dan.Torbati{at}MCH.com
 |
Abstract
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Objectives: We tested the hypothesis that an increase
in the blood colloid osmotic pressure (COP) that is maintained during
early-stage endotoxemia may decrease fluid flux across capillaries and
may reduce pulmonary and multiple-organ edema.
Design:
Prospective study.
Settings: Research laboratory in a
hospital.
Subjects: Male albino Sprague-Dawley
rats.
Interventions: Rats were anesthetized with
pentobarbital, underwent tracheotomies, were cannulated in the femoral
vein and artery, and were randomly assigned to the following four
groups comprising 11 rats each: group I, controls (saline solution
treatment); group II, albumin treatment (three doses of 1 g/kg 25%
human albumin every 2 h); group III, endotoxin treatment with a
single IV dose of 4 mg/kg endotoxin; and group IV, endotoxin and
albumin-treatment (4 mg/kg endotoxin plus albumin treatment).
Experiments lasted for 6 h while fluid intake was equally
maintained in all groups.
Measurements and results:
COP and other variables were measured every 2 h. To determine the
water content of an organ, after the rat was killed, the lung, heart,
kidney, intestine, and liver were removed. Albumin treatment alone
(group II) generated significant increases in COP (maximum, 58% from
the baseline measurement) but did not change the water content of the
organ, compared with saline solution-treated controls.
Endotoxin-treated rats (group III) developed significant reductions in
COP, with significant increases in pulmonary, renal, and heart water
content compared with controls. Albumin treatment in endotoxemic rats
(group IV) significantly increased the COP without improving the
endotoxemia-induced organ edema. Pulmonary edema, however, was
increased further, compared with endotoxemia alone.
Conclusions: COP elevation by albumin administration during
the early stage of endotoxemia does not ameliorate pulmonary or
multiple-organ edema and may aggravate pulmonary
edema.
Key Words: colloid osmotic pressure • edema • endotoxemia • pulmonary edema • sepsis
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Introduction
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Colloid
osmotic pressure (COP) is generated across membranes that are permeable
to water and low-molecular-weight substances but that are impermeable
to large molecular compounds, such as plasma proteins. Fluid
administration is a fundamental part of resuscitation therapy, which is
performed by using either crystalloid or colloid solutions. Crystalloid
solutions, such as Ringer’s lactate solutions and saline solutions,
supply water and sodium to intravascular and extravascular
compartments. Colloid solutions, such as those containing albumin,
dextrans, or starches, increase the plasma COP and may shift fluid from
the interstitial compartment to the intravascular compartment.
Increased capillary permeability promotes the distribution of water
from the intravascular to the interstitial space, leading to the
development of multiple-organ edema, including pulmonary edema. This
occurs in a wide variety of clinical disorders, including ARDS, sepsis,
and septic shock, as well as head or body trauma.1
Animal
models demonstrate that a multitude of endogenous vasodilator
mediators, including oxygen free radicals, prostaglandins,
leukotrienes, and tumor necrosis factor, are associated with increased
capillary permeability.1
A continuing controversial
question for the treatment of critically ill patients is which of the
two major strategies, namely, colloid or crystalloid therapy, should be
used to ameliorate the effects of increased capillary permeability and
hypovolemia.2
3
4
5
6
7
Fluid transport across capillaries is a very complex
chemophysical process, taking place at variable stages of different
critical-care conditions. In general, fluid transport is defined by the
Starling equation as a function of the following variables: (1)
microvascular (capillary) hydrostatic pressure; (2) perimicrovascular
hydrostatic pressure; (3) plasma COP; (4) COP of the interstitial
fluid; (5) fluid conductance across capillary membrane (coefficient of
filtration); and (6) the reflection coefficient (measures the extent to
which the semipermeable membrane prevents egress of plasma proteins). A
further dynamic factor, which is not included in the Starling equation,
is the ability of the lymphatic system to clear fluid from the
interstitium. Alterations in these forces influence the interstitial
fluid accumulation (ie, edema formation).
According to Starling principles, the plasma COP is one of the major
factors affecting fluid flux across the capillaries. However, the role
of COP in modulating the fluid flux across the capillary membrane in
critically ill patients is controversial. Two reviews8
9
concluded that albumin-treated patients have a 4 to 6% excess
mortality rate compared to crystalloid-treated patients. In contrast,
Choi et al10
have concluded that there is no difference in
mortality rate between the crystalloid-treated patients and the
colloid-treated patients. Concerning fluid flux in individual organs,
increasing COP during normothermic cardioplegia can minimize myocardial
edema.11
In a rat model, Belayev et al12
demonstrated that a high dose of albumin therapy, 5 min after creating
global cerebral ischemia, significantly improved the neurologic scores
and reduced histologic changes. During sepsis, however, an increase in
the capillary permeability is generalized.13
14
The
complex factors of fluid transport across the membrane with capillary
leakage and decreased COP, as well as the design of different studies,
are the major factors that prevent studies to reach conclusive clinical
guidelines for fluid resuscitation.15
In the present study, we utilized a rat model in which gas-exchange
efficiency and hemodynamic stability were measured under strictly
controlled anesthesia, with variable environmental
conditions.16
17
We also tried to eliminate confounding
factors that may complicate the outcome, such as the administration of
different volumes of fluids in different groups to achieve a
"normal" end point. Our hypothesis is that an increase in blood COP
that is maintained during an early stage of endotoxemia may decrease
fluid flux across capillaries and may reduce pulmonary and
multiple-organ edema.
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Materials and Methods
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Anesthesia, Surgery, and Fluid Balance
The experimental protocol for this study was approved by the
Institutional Animal Care and Use Committee of the Miami Children’s
Hospital, Miami, FL. Young albino Sprague-Dawley rats (weight range,
250 to 350 g) were anesthetized with 50 mg/kg pentobarbital
intraperitoneally. In the supine position, a tracheostomy was
performed and an endotracheal tube (7F scale; Becton Dickinson; Sparks,
MD) was advanced to a position approximately 1 cm above the
carina. Subsequently, a femoral vein and a femoral artery were exposed
and cannulated. Each rat then was placed over an electric heating
blanket, and the rectal temperature (TH-5, Physitemp; Thermalert;
Clifton, NJ with a rat size thermal probe), the mean
arterial BP (MABP), and heart rate (HR) [model 2001A; Datascope Corp;
Paramus, NJ] were continuously monitored. Normothermia (mean ± SD,
38 ± 0.5°C) was established, while anesthesia and fluid
balance, respectively, were strictly maintained by the administration
of pentobarbital, 15 mg/kg/h, and by saline solution, 7.5 mL/kg/h IV
(Medfusion pump 2010; Medex; Duluth, CA). The dose of 15 mg/kg/h
pentobarbital has been shown to maintain a stable anesthesia for > 6
h in male rats.16
Previously, we have used 5 mL/kg/h
saline solution to maintain fluid balance in anesthetized rats that had
been subjected to various critical-care conditions in order to maintain
hemodynamic stability over a 6-h period.16
17
In the
present study, anticipating some hemodynamic instability with
endotoxemia, we used a higher volume of 7.5 mL/kg/h saline solution. To
avoid confounding factors, this volume was given to both control rats
and treatment-group rats. During the entire experimental period, all
animals were breathing room air spontaneously.
Experimental Groups
Thirty to 45 min after the completion of all invasive
procedures, the baseline values for blood COP (Osmometer model 4420;
Wesco, Inc; Logan, UT), MABP, HR, gas-exchange variables (ABL-30 Blood
Gas Analyzer; Radiometer; Copenhagen, Denmark), hemoglobin (Hb), and
Hb-oxygen saturation (HbO2) [model OSM3
hemoxymeter; Radiometer] were determined. The
PaO2,
PaCO2, and pH values were corrected
for body temperature. An equivalent volume of saline solution replaced
the blood volume that had been removed for various analyses. According
to our previous experience with similarly instrumented rat
models,16
17
a dose of up to 100 U/kg/h heparin is needed
to maintain the openness of venous and arterial lines. This dose of
heparin also prevents blood coagulation in samples used for
gas-exchange analyses or COP determination. However, to minimize the
possible interaction of heparin with the endotoxin, we used a reduced
dose of 100 U/kg/2 h IV. Assuming that the presence of heparin can
block the activity of endotoxin, it may then equally affect the
severity of endotoxemia in both saline solution-treated and
albumin-treated endotoxemic rats. The rats were then randomly assigned
to one of the following experimental groups (n = 11 in each
group).
Group I (Saline Solution-Treated Rats):
These control rats
received three volumes of 4 mL/kg saline solution immediately after
collecting data for the baseline (zero hour), and at 2 and 4 h
later (a total of 12 mL/kg within a 4-h period, in addition to the 7.5
mL/kg/h saline solution that was continuously used to maintain fluid
balance). This additional volume of saline solution was equivalent to a
volume of 1 g/kg per dose of 25% albumin, given in the following
albumin-treated groups. All variables that had been measured at
baseline were measured again at 2, 4, and 6 h.
Group II (Albumin-Treated Rats):
These rats were treated
exactly as those in group I, but, instead of saline solution boluses,
they received three doses of 1 g/kg 25% human albumin in equivalent
volumes. This dose of albumin is used for improving COP in infants and
children. In our preliminary trials with endotoxemia, lower doses of
albumin (ie, 0.5 g/kg/h for 4 h) did not increase
COP above the baseline. Therefore, we used three boluses of 1 g/kg 25%
human albumin at 0, 2, and 4 h of the experiments in order to
maintain a high COP level.
Group III (Endotoxin-Treated Rats):
After data for the
baseline levels were collected, these rats were given a single dose of
4 mg/kg endotoxin IV (Escherichia coli
lipopolysaccharide; Detico Laboratories; Detroit, MI) and then were
treated as in group I.
Group IV (Endotoxin-Albumin-Treated Rats):
These rats were
given a single dose of 4 mg/kg endotoxin as in group III, followed by
three doses of albumin as in group II.
Determination of Organ Water Content
After the last data collection (at 6 h), all rats were
killed with IV administration of pentobarbital, following which the
kidneys, lung, heart, liver, and a 15-cm section of the ileum in each
rat were quickly removed. Tissues were weighed and then placed in an
oven at 60°C for slow drying for > 5 days. Dry weights then were
measured, and wet/dry weights were calculated for the determination of
organ water content.
Statistical Analysis
All values are presented as the mean ± SD. Data at various
time points within the same group were evaluated by repeated measures
of analyses of variance, followed by the Dunnett multiple comparisons
test. For this analysis, the values at time zero were compared with the
measurements taken at 2, 4, and 6 h. Differences among the four
groups at comparable time periods were evaluated with analyses of
variance followed by the Tukey-Kramer multiple comparisons test. This
test also was used to find the differences in the water content of the
organ among all groups. Data analyses were performed only on surviving
rats and/or those that completed the 6-h experimental period.
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Results
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Group I
Experiments in this group were completed in 10 of 11 rats. The
gas-exchange variables showed continued and significant increases in
PaO2 level, which were accompanied by
significant decreases in PaCO2 level
and a stable pH level (Table 1
). The COP was significantly reduced within 2 to 6 h (Fig 1
). In these rats, as in all other groups, an estimated 10 mL/kg blood
was removed for different analyses and was replaced by saline solution.
A gradual reduction in the Hb concentration from 14.4 ± 0.6 to
12.6 ± 0.8 g/dL was observed after 6 h (Fig 2
), with a 10% reduction in the arterial O2
content (Fig 3
). The alveolar-arterial O2 pressure difference
(P[A-a]O2) was significantly reduced by 30%
throughout the experiment (Fig 4
). No significant changes occurred in MABP (Fig 5
) and HR (Fig 6
).
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Table 1. Gas Exchange and Blood COP During 6 h of
Maintained Anesthesia in 10 Spontaneously Breathing, Saline
Solution-Treated Rats*
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Figure 1. Changes in blood COP in healthy rats (controls)
and healthy rats that received albumin treatment, as well as following
endotoxemia with or without albumin treatment. Endotoxin was
administered IV immediately after the baseline values were determined
(time zero). Boluses of 1 g/kg human albumin were administered IV
immediately after time zero and at 2 and 4 h afterward.
* = p < 0.05 (differences within the same group, comparing
baseline values with those measured 2, 4, and 6 h later using
repeated measures of analysis of variance followed by Dunnett multiple
comparisons test).
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Figure 2. Changes in Hb concentrations in healthy rats
(controls) and healthy rats that received albumin treatment, as well as
following endotoxemia with or without albumin treatment. For drug
administrations and statistical comparison, see Figure 1
.
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Figure 3. Changes in arterial O2 content in
healthy rats (controls) and healthy rats that received albumin
treatment, as well as following endotoxemia with or without albumin
treatment. For drug administration and statistical comparison, see
Figure 1
. The O2 content at 6 h in the
endotoxin-albumin-treated group is significantly lower than that in all
other groups (Tukey-Kramer multiple comparisons test).
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Figure 4. Changes in P(A-a)O2 in saline
solution-treated ("healthy") rats and rats that received albumin
treatment, as well as following endotoxemia with or without albumin
treatment. For drug administration and statistical comparison, see
Figure 1
. Endotoxin-albumin-treated rats demonstrated
significantly higher P(A-a)O2 values, compared to
those of all other groups.
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Figure 5. Changes in MABP in healthy rats (controls) and
healthy rats that received albumin treatment, as well as following
endotoxemia with or without albumin treatment. For drug administration
and statistical comparison, see Figure 1
. Albumin treatment during
endotoxemia created a consistently higher MABP than endotoxemia by
itself.
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Figure 6. Changes in HR in healthy rats (controls) and
healthy rats that received albumin treatment, as well as following
endotoxemia with or without albumin treatment. For drug administrations
and statistical comparison, see Figure 1
. Endotoxin treatment both
alone and in combination with albumin treatment generated significant
increases in HR, which was more pronounced in the latter group.
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Group II
Experiments in this group were completed in 10 of 11 rats, the
results showed stable gas-exchange and acid-base balances (Table 2
). The infusion of the three single doses of 1 g/kg human albumin was
associated with a gradual and significant increase in COP up to a
maximum of 58% (Fig 1)
. In this group, decreases in the Hb
concentration were larger than those in saline solution-treated animals
(Fig 2)
. Consequently, arterial O2 content was
significantly reduced by > 15% (Fig 3)
. There were no significant
changes in P(A-a)O2 (Fig 4)
, MABP (Fig 5)
, or HR
(Fig 6)
.
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Table 2. Gas Exchange and Blood COP During 6 h of
Maintained Anesthesia in 10 Spontaneously Breathing Albumin-Treated
Rats*
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Group III
Ten of 11 rats in this group survived the 6-h experimental period
following a single dose of 4 mg/kg endotoxin and saline solution
infusions. PaO2 was significantly
increased, as early as 2 h after endotoxin injection (Table 3
), while PaCO2 was decreased.
Endotoxemia was associated with a further decrease in the COP compared
to saline solution-treated rats (Fig 1
; Tukey-Kramer multiple
comparisons test). Starting 4 h after endotoxin injection, Hb and
arterial O2 content were reduced significantly.
These reductions were similar to those observed in the saline
solution-treated rats (Figs 2
, 3)
. The P(A-a)O2
did not change throughout the experiment (Fig 4)
. Unlike the results
for group I, endotoxemia caused a > 20% reduction in MABP starting
at 4 h following endotoxin injection (Fig 5)
, while HR was
significantly increased starting at 2 h following endotoxin
injection (Fig 6)
.
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Table 3. Gas Exchange and Blood COP During 6 h of
Maintained Anesthesia in 10 Spontaneously Breathing Endotoxin-Treated
Rats*
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Group IV
Nine of 11 rats in this group survived the combined treatment of
endotoxin and albumin. PaO2 was
gradually reduced, reaching a significant level (18%) by 6 h.
PaCO2, however, was reduced
significantly at 2 h and 6 h (28% and 39%, respectively;
Table 4
). COP gradually increased, becoming significant at 6 h (Fig 1)
.
This rate of increase in COP was significantly less than that in the
rats treated with albumin alone (Fig 1)
. Endotoxin-albumin treatment
caused the highest degree of Hb reduction (Fig 2)
and arterial
O2 content (Fig 3)
. Plasma in these rats (tested
in four cases) showed no free Hb, indicating a lack of hemolysis.
Endotoxin-albumin-treated rats showed comparable reductions in MABP and
increases in HR compared to those in the endotoxin-treated group (Figs 5
, 6)
.
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Table 4. Gas Exchange and Blood COP During 6 h of
Maintained Anesthesia in Nine Spontaneously Breathing Endotoxemic Rats
Treated With Three Boluses of 1 g/kg Human Albumin Every 2
h*
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Organ Water Content
Ileum and liver water content was not significantly different in
any group (saline solution-treated rats: liver, 72.3 ± 1.0%; ileum,
76.2 ± 0.87). In contrast, however, significant differences were
observed for the lung, the kidneys, and the heart among the various
groups (Fig 7
). Lung water content increased significantly in the endotoxemic
rats (group III) and rats that were treated with both endotoxin and
albumin (group IV) compared to saline solution-treated rats and
albumin-treated rats (controls, 79.82 ± 0.63%; rats with
endotoxemia, 80.89 ± 0.81%; and endotoxin-albumin treated rats,
82.19 ± 0.61). Endotoxin-albumin treatment produced
significantly higher levels of pulmonary edema than those with
endotoxin treatment alone. The water content of the heart and kidney
were significantly higher in both endotoxin-treated and
endotoxin-albumin-treated animals compared to the saline
solution-treated controls. Albumin treatment alone produced no
significant differences in the water content of lung, kidney, and heart
when compared to that in the controls (Fig 7)
.
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Figure 7. The water content of multiple organs in saline
solution-treated and albumin-treated rats (controls) and in endotoxemic
rats with or without albumin treatment. * = p < 0.05 (all
groups are compared by one-way analysis of variance, followed by
Tukey-Kramer multiple comparison test). The increase in the lung water
content of endotoxemic rats was significantly higher than that of
endotoxemia with albumin treatment.
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Discussion
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Our data demonstrate that increasing COP by albumin infusion
during an early stage of endotoxemia with capillary leak syndrome is
associated with significant increases in P(A-a)O2
[Fig 4
], as well as reductions in Hb (Fig 2)
, arterial
O2 content (Fig 3)
, and O2
carrying capacity. Concurrently, systemic and pulmonary hemodynamics
become unstable compared with those variables in endotoxemic rats that
had not received albumin therapy (Figs 5
, 6)
. The postmortem water
content evaluation of multiple organs in endotoxemic rats that had
received albumin treatment also shows significant increases in the
water content of lung, heart, and kidney (Fig 7)
. The increase in
pulmonary edema associated with albumin treatment in endotoxemic rats
confirms the results of Ernest et al,3
who studied the
distribution of normal saline solution and 5% albumin infusions in
septic patients. Clinically, fluid resuscitation for circulatory shock
(due to hemorrhage or sepsis) is carried out to a physiologic end point
such as normotension. This requires using a two to three times higher
volume of crystalloid solutions compared to that for colloid
solutions.1
2
3
Because the primary aim of our
experiment was to investigate the effect of high COP on fluid
redistribution, we used an equal fluid volume for both the saline
solution-treated and the albumin-treated groups. Thus, the present data
may not be extrapolated to the clinical situations involving fluid
resuscitation. Furthermore, the albumin-treated groups in our study
created a higher degree of reduction in Hb concentration, compared to
the saline solution-treated groups (Fig 2)
. Such an effect, which may
be related to a larger degree of hemodilution (as judged by the lack of
hemolysis, which was tested in four plasma samples), can affect the
blood oxygen carrying capacity.
Our observations are not consistent with a number of studies that have
evaluated the effect of crystalloid and colloid infusions during
increased capillary permeability on extravascular lung water content.
For example, Rackow et al18
found no difference in lung
and muscle extravascular water content after saline solution or
hetastarch infusion in five septic rats with cecal ligation and
perforation compared to a group of five control rats. However, Rackow
et al18
found significantly lower plasma COP levels
(9.3 ± 0.5 mm Hg) in saline solution-infused rats than in
hetastarch-infused rats (21.6 ± 0.5 mm Hg) compared to control
animals (16.1 ± 1.2 mm Hg). Similarly, Rutili et al19
found that dextran infusion in lung-injured dogs did not increase lung
water content compared with saline solution infusion. Moreover, septic
baboons have shown pulmonary dysfunction that is independent of the
plasma COP.20
These contrasting reports may reflect the
effect of dynamically changing capillary permeability during sepsis.
In the absence of increased capillary permeability, low oncotic
pressures predispose animals to increased levels of extracellular lung
water.21
22
23
For example, in hypoproteinemic dogs, without
acute lung injury, crystalloid infusion increased the amount of lung
water compared with colloid infusion.21
McKeen et
al22
also found that saline solution infusion can increase
extravascular lung water in sheep with hemorrhage-induced
hypoproteinemia compared to colloid infusion. Guyton and
Lindsey23
demonstrated that when plasma COP was reduced by
half, the threshold hydrostatic pressure necessary for the formation of
pulmonary edema fell from 25 to 13 mm Hg. An increase in the
hydrostatic pressure above a threshold appears to be a prerequisite for
edema formation.23
When capillary permeability is
increased, the transvascular oncotic pressure gradient is
decreased.24
25
In this setting, the hydrostatic pressure
will be the major determinant of pulmonary edema, rather than oncotic
pressure. The MABP in our endotoxemic rat model was decreased by 20%
(Fig 5)
at 4 h following endotoxin infusion. It is possible that
increased capillary permeability may decrease the hydrostatic pressure
threshold for pulmonary dysfunction.20
Reduced plasma COP
with normal permeability, however, can decrease the hydrostatic
pressure threshold, which is necessary for edema
formation.23
Ernest et al3
showed that, in septic patients, saline
solution infusion increased extracellular fluid volume by approximately
the volume infused and the infusion of 5% albumin increased
extracellular fluid volume by double the volume infused, indicating
fluid movement from the intracellular space to extracellular space. We
speculate that in our rat model albumin infusion increased
intravascular fluid volume by shifting fluid from the intracellular
compartment. This scenario, in endotoxin-albumin-treated rats, may
result in increased capillary hydrostatic pressure and increased
extravasation of fluid from the vascular compartment, when compared to
endotoxemic rats that were not treated with albumin. In fact, the MABP
was consistently higher in endotoxin-albumin-treated rats than in
endotoxemic rats (Fig 5)
. Whether increased capillary hydrostatic
pressure in this rat model is ultimately responsible for a larger
pulmonary edema formation warrants investigation.
Extrapulmonary Effects of COP
Hetastarch and pentastarch infusion in hypoproteinemic sheep,
unlike our endotoxemic albumin-treated rats, have produced a limited
transvascular fluid filtration in the lung and soft tissue compared to
crystalloid infusion.22
This, however, was explained by
the augmentation of plasma COP and by the plasma-to-lymph oncotic
pressure gradient, where capillary integrity was
maintained.22
Conflicting reports of the role of COP in
the formation of organ edema indicate that the other Starling forces
have significant but varying influence on edema genesis. Mehlhorn et
al11
reported that increasing the COP of normothermic
blood cardioplegia minimizes myocardial edema, thus preventing
post-cardiopulmonary bypass cardiac dysfunction. Long-term high-colloid
oncotic therapy was found to be effective in reducing ischemic brain
edema in gerbils.26
In a rat model, reduced COP aggravated
brain edema after mild-to-moderate mechanical head
injury.27
Interstitial pressure is another factor that influences fluid flux
across the capillary membranes. This pressure in muscles is equal to 0
mm Hg.28
Although negative values are found in the lung,
positive pressures are recorded in organs with tight capsules such as
the kidney, in which values of 8 to 10 mm Hg have been
reported.29
Interstitial compliance and interstitial
pressure are different in various organs. This also may be one of the
factors responsible for the varying degree of interstitial edema
formation in different organs. Thus, while an increase in capillary
permeability during sepsis is generalized,13
it may affect
different organs to various degrees. Increased water content may
disturb functional activity by reducing tissue oxygenation. This may
contribute to multiple organ dysfunction, as seen in sepsis and other
systemic inflammatory reaction syndromes.
Albumin treatment both with and without endotoxemia led to significant
decreases in Hb levels (Fig 2)
, probably due to hemodilution. This may
increase transcapillary fluid movements by affecting plasma COP, the
capillary surface area, or capillary permeability.30
Thus,
albumin administration for increasing COP may indirectly affect
O2 carrying capacity. Alternatively, the easiest
way for increasing COP is to give large doses of diuretics, whereas the
easiest way of reducing COP is to give large volumes of
crystalloids.31
Furosemide, a diuretic agent, has been
shown to enhance pulmonary edema clearance in dogs.32
Whether increasing COP by giving furosemide or other diuretic agents
will improve multiple-organ edema during endotoxemia warrants further
investigation.
|
Conclusions
|
|---|
Artificially increasing COP by albumin administration, in the face
of early global capillary leak syndrome, aggravates pulmonary
dysfunction and appears to have no beneficiary effect on
endotoxin-induced lung, kidney, or heart edema.
|
Acknowledgements
|
|---|
The authors thank Wescor, Inc, Logan, UT, for
the provision of a colloid osmometer instrument (model 4420) for this
project.
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Footnotes
|
|---|
Abbreviations: COP = colloid osmotic pressure;
Hb = hemoglobin; HbO2 = hemoglobin-oxygen saturation;
HR = heart rate; MABP = mean arterial BP;
P(A-a)O2 = alveolar-arterial oxygen pressure difference
This study was partially supported by research grants from Miami
Children’s Foundations (Dr. Torbati).
Received for publication October 24, 2000.
Accepted for publication May 2, 2001.
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References
|
|---|
-
Haupt, MT, Kaufman, BS, Carlson, RW (1992) Fluid resuscitation in patients with increased vascular permeability. Crit Care Clin 8,341-353[ISI][Medline]
-
Roberts, JS, Bratton, SL (1998) Colloid volume expanders: problems, pitfalls and possibilities. Drugs 55,621-630[CrossRef][ISI][Medline]
-
Ernest, D, Belzberg, AS, Dodek, PM (1999) Distribution of normal saline and 5% albumin infusions in septic patients. Crit Care Med 27,46-50[CrossRef][ISI][Medline]
-
Allison, SP, Lobo, DN (2000) Debate: albumin administration should not be avoided. Crit Care 4,147-150[CrossRef][ISI][Medline]
-
Pulimood, TB, Park, GR (2000) Debate: albumin administration should be avoided in the critically ill. Crit Care 4,151-155[CrossRef][ISI][Medline]
-
Blunt, MC, Nicholson, JP, Park, GR (1998) Serum albumin and colloid osmotic pressure in survivors and nonsurvivors of prolonged critical illness. Anesthesia 53,755-761[CrossRef][ISI][Medline]
-
Rackow, EC, Fein, IA, Leppo, J (1977) Colloid osmotic pressure as a prognostic indicator of pulmonary edema and mortality in the critically ill. Chest 72,709-713[Abstract/Free Full Text]
-
Schierhout, G, Roberts, I (1998) Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomized trials. BMJ 316,961-964[Abstract/Free Full Text]
-
Alderson, P, Bunn, F, Lefebvre, C, et al (1998) Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 317,235-240[Abstract/Free Full Text]
-
Choi, PT, Yip, G, Quinonez, LG, et al (1999) Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care Med 27,200-210[CrossRef][ISI][Medline]
-
Mehlhorn, U, Allen, SJ, Davis, KL, et al (1998) Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction. Cardiovasc Surg 6,274-281[CrossRef][ISI][Medline]
-
Belayev, L, Saul, I, Huh, PW, et al (1999) Neuroprotective effect of high-dose albumin therapy against global ischemic brain injury in rats. Brain Res 845,107-111[CrossRef][ISI][Medline]
-
Ellman, H (1984) Capillary permeability in septic patients. Crit Care Med 12,629-633[ISI][Medline]
-
Astiz, ME, Galera-Santiago, A, Rackow, EC (1993) Intravascular volume and fluid therapy for severe sepsis. New Horizons 1,127-136[Medline]
-
Astiz, ME, Rackow, EC (1999) Crystalloid-colloid controversy revisited [editorials]. Crit Care Med 27,34-35[CrossRef][ISI][Medline]
-
Torbati, D, Ramirez, J, Hon, E, et al (1999) Experimental critical care in rats: gender differences in anesthesia, ventilation and gas-exchange. Crit Care Med 27,1878-1884[CrossRef][ISI][Medline]
-
Torbati, D, Camacho, MT, Raszynski, A, et al (2000) Effect of hypothermia on ventilation in anesthetized, spontaneously breathing rats: theoretical implications for mechanical ventilation. Intensive Care Med 26,585-591[CrossRef][ISI][Medline]
-
Rackow, EC, Astiz, ME, Schumer, W, et al (1989) Lung and muscle water after crystalloid and colloid infusion in septic rats: effect on oxygen delivery and metabolism. J Lab Clin Med 113,184-189[ISI][Medline]
-
Rutili, G, Parker, JC, Taylor, AE (1984) Fluid balance in ANTU-injured lungs during crystalloid and colloid infusions. J Appl Physiol 56,993-998[Abstract/Free Full Text]
-
Kohler, JP, Rice, CL, Zarins, CK, et al (1981) Does reduced colloid oncotic pressure increase pulmonary dysfunction in sepsis? Crit Care Med 9,90-93[ISI][Medline]
-
Rackow, EC, Weil, MH, Macneil, AR, et al (1987) Effects of crystalloid and colloid fluids on extravascular lung water in hypoproteinemic dogs. J Appl Physiol 62,2421-2425[Abstract/Free Full Text]
-
McKeen, CR, Bowers, RW, Harris, JR, et al (1986) Saline compared to plasma volume replacement after volume depletion in sheep: lung fluid balance. J Crit Care 1,133-141
-
Guyton, AC, Lindsey, AW (1959) Effect of elevated left atrial pressure and decreased plasma protein concentration on the development of pulmonary edema. Circ Res 7,649[Abstract/Free Full Text]
-
Brigham, KL, Woolverton, WC, Blake, LH, et al (1974) Increased sheep lung vascular permeability caused by pseudomonas bacteremia. J Clin Invest 54,792-804
-
Nylander, WAJ, Hammon, JWJ, Roselli, RJ, et al (1981) Comparison of the effects of saline and homologous plasma infusion on lung fluid balance during endotoxemia in the unanesthetized sheep. Surgery 90,221-228[ISI][Medline]
-
Hakamata, Y, Ito, U, Hanyu, S, et al (1995) Long-term high-colloid oncotic therapy for ischemic brain edema in gerbils. Stroke 26,2149-2153[Abstract/Free Full Text]
-
Drummond, JC, Patel, PM, Cole, DJ, et al (1998) The effect of the reduction of colloid oncotic pressure, with and without reduction of osmolality, on post-traumatic cerebral edema. Anesthesiology 88,993-1002[CrossRef][ISI][Medline]
-
Wiig, H, Reed, RK (1987) Volume-pressure relationship (compliance) of interstitium in dog skin and muscle. Am J Physiol 253(suppl),H291-H298[Abstract/Free Full Text]
-
Granger, JP, Haas, JA, Pawlowska, D, et al (1988) Effect of direct increases in renal interstitial hydrostatic pressure on sodium excretion. Am J Physiol 254,F527-F532[Abstract/Free Full Text]
-
Wiederhielm, CA (1968) Dynamics of transcapillary fluid exchange. J Gen Physiol 52,29-61[Abstract]
-
Webb, AR (1999) Crystalloid or colloid for resuscitation: are we any the wiser? Crit Care 3,R25-R28[CrossRef][ISI][Medline]
-
Ali, J, Duke, K (1987) Colloid osmotic pressure in pulmonary edema clearance with furosemide. Chest 92,540-545[Abstract/Free Full Text]
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Abstract
Introduction
