Open Journal of Anesthesiology, 2013, 3, 396-401
Published Online November 2013 (http://www.scirp.org/journal/ojanes)
http://dx.doi.org/10.4236/ojanes.2013.39084
Open Access OJAnes
Changes in Blood Volume and Colloid Osmotic Pressure
during Fluid Absorption in Patients Undergoing
Endoscopic Urosurgery: An Observational Study*
Kaori Yagi1, Chihiro Kamagata1, Masashi Ishikawa1, Yukihiro Kondo2, Atsuhiro Sakamoto1
1Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2Depart-
ment of Urology, Nippon Medical School, Tokyo, Japan.
Received September 8th, 2013; revised October 1st, 2013; accepted October 17th, 2013
Copyright © 2013 Kaori Yagi et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background and Objective: Anesthesiologists need to be familiar with perioperative changes in blood volume (BV);
however, there is no standard method for repeated evaluation of BV over a short interval of time. We evaluated BV in
the operation room using repeatable estimation methods. Method: Eighty-five ASA physical status I-II patients sched-
uled to undergo endoscopic urosurgery using irrigation fluid under general anesthesia at Nippon Medical School Hos-
pital were included in this study. Irrigation with 3% sorbitol in water was commenced after establishment of general
anesthesia and volumetric fluid balance, which was defined as control water balance (WB). Hematocrit (Hct), colloid
osmotic pressure (COP), total protein (TP) and albumin (Alb) were repeatedly determined before and during anesthesia.
BV was calculated using Allen’s formula and the changes in Hct, COP, TP and Alb. Main Outcome Measures: The
main outcome was the accuracy of measuring changes in BV (∆BV) calculated using the four serum markers. WB and
the estimated ∆BV calculated from Hct, COP, TP and Alb (∆BV-Hct, ∆BV-COP, ∆BV-TP, and ∆BV-Alb) were ana-
lysed using Pearson’s correlation coefficient test and Bland-Altman analysis. Results: Sixty-five patients were excluded.
In the remaining 20 patients, there was a significant correlation between WB and ∆BV-COP (R2 = 0.72; P < 0.01), WB
and ∆BV-TP (R2 = 0.59; P < 0.01) and WB and ∆BV-Alb (R2 = 0.57; P < 0.01), while there was no correlation between
WB and ∆BV-Hct (R2 = 0.06). Conclusion: ∆BV-COP, ∆BV-TP and ∆BV-Alb had correlation with WB. However,
since COP can be measured repeatedly with simplified instruments under selected clinical circumstances, while TP and
Alb cannot. COP is the most useful marker to measure ∆BV during perioperative period. Hct does not allow precise
estimation of ∆BV.
Keywords: Colloid Osmotic Pressure; Blood Volume; Perioperative Period
1. Introduction
Measurement of blood volume (BV) is a perioperative
concern for the anesthetist. The standard method for
measuring BV directly is the marker dilution technique,
using a radioisotope [1,2]. However, it is difficult to use
this method for serial measurements of BV over a short
interval of time because radioisotopes must be used in a
special radiation-permitted area, and these tracers are
retained in the blood for days. Yet, it is necessary for us
to be able to measure BV safely, repeatedly, accurately
and conveniently. Therefore, we questioned whether a
substance that naturally occurs in the intravascular
space could be used as an indicator of plasma dilution,
allowing safe and repeated measurements without admi-
nistration of a dilution drug. Previously, changes in he-
matocrit (Hct), total protein (TP) and plasma colloid os-
motic pressure (COP) have been used to estimate changes
in BV in patients undergoing minor surgery under ge-
neral anesthesia [3]. Although these markers can be mea-
sured safely, repeatedly, accurately and conveniently, it
was not clear which of these markers are accurate re-
presentatives of actual BV changes. The purpose of this
study was to evaluate the accuracy of measuring changes
in BV using Hct, COP, TP, and albumin (Alb) as dilution
markers, to determine the most useful marker during the
perioperative period.
*Conflicts of interest: None declared.

Changes in Blood Volume and Colloid Osmotic Pressure during Fluid Absorption in
Patients Undergoing Endoscopic Urosurgery: An Observational Study
397
2. Patients and Methods
The study protocol was registered with the UMIN Clini-
cal Trials Registry (Trial No. UMIN000007560). Ethical
approval for this study (Protocol number 223009) was
provided by the Institutional Review Board of Nippon
Medical School Hospital, Tokyo, Japan, (Chairperson:
Hospital director Y Fukunaga) on 30 November 2011.
We obtained written informed consent from all patients
the day before surgery. Eighty-five male patients under-
going transurethral resection of bladder tumors (TUR-Bt)
and transurethral resection of the prostate (TUR-P) at the
Nippon Medical School Hospital between April 2012 and
March 2013 were included in this study. All patients
were American Society of Anesthesiologists (ASA) phy-
sical status I-II, with no preexisting renal, hepatic or se-
vere heart disease.
All patients fasted from 9 pm on the eve of surgery,
and no intravenous fluids were administered before the
induction of anesthesia. On arrival at the operating room,
a 22-G cannula was placed in the left radial artery under
local anesthesia with 1% lidocaine, for collection of
blood samples during the study period. Before anesthesia,
Hct, TP, Alb and COP were measured. These parame-
ters were also measured 30 min after the induction of
anesthesia, at which time irrigation was started (Anesth-
30), and then at 30-min intervals thereafter during
anesthesia (i.e., Anesth-60, Anesth-90 etc.). We also col-
lected blood samples at the end of the surgical procedure
(“Anesth-end”) and 30 min after tracheal extubation
(“Recovery”). A flow chart of the timing of blood sam-
pling following anesthesia and irrigation is shown in Fi-
gure 1.
After baseline measurements, a peripheral intravenous
cannula (20-G) was inserted to administer normal saline
throughout the study period, at a rate of 1 mL·kg−1·h−1,
using an infusion pump. Hct, TP and Alb were measured
using standard techniques. COP was measured with a
colloid osmometer (Colloid-4420, Wescor Inc., Logan,
UT, USA). The colloid osmometer employs a method
referred to as transudation, which involves passing water
molecules and diffusible solute particles through a
synthetic semi-permeable membrane that has a diffusion
cut-off of 30,000 Da [4]. The membrane separates the
“Awake” “Anesth-30”
“Anesth-60” “Anesth-end” “Recovery”
Figure 1. Schematic diagram of the study protocol.
specimen solution from a reference solution after the
samples are injected into the reference chamber. The fluid
then moves through the membrane and into the sample
chamber until the hydrostatic pressure reaches equili-
brium. This pressure is measured by a piezoelectric pres-
sure transducer.
General anesthesia was induced with propofol (2.0
mg·kg−1) and rocuronium (0.6 mg·kg−1). Endotracheal
intubation was performed about 5 min after induction.
Patients were mechanically ventilated with oxygen (2
L·min−1) and air (4 L·min−1) at a tidal volume of 8
mL·kg−1 and respiratory rate of 8 - 12 breaths·min−1, to
maintain an end-tidal CO2 of 35 - 40 mmHg during the
anesthetic period. Anesthesia was maintained with sevo-
flurane supplemented with remifentanil (0.1 g·kg−1·min−1).
The sevoflurane concentration was controlled to maintain
SBP within 80% - 120% of awake values. If hypotension
occurred, it was treated with 4 mg ephedrine intrave-
nously. At the end of surgery, sevoflurane and remifen-
tanil were discontinued, and sugammadex (4 mg·kg−1)
was injected to reverse the effects of rocuronium. Pos-
toperatively, the patients were left undisturbed while
breathing supplemental oxygen (6 L·min−1) administered
via a face mask.
The BV of each patient was calculated using the for-
mula of Allen and colleagues (BVAllen) [5], which indica-
tes the BV in the awake condition [6,7].
Equation for males: BVAllen = 0.417 × height3 (m) +
0.045 × body weight (kg) – 0.03 (L)
BV at each sampling time was estimated from the ba-
seline BVAllen and the subsequent changes in Hct, COP,
TP and Alb respectively. For example, BV estimated
from the change in COP (BV-COP) at “Anesth-30” was
calculated by the following formula:
BV-COP (Anesth-30) = BVAllen (Awake) × [COP
(Awake)/COP (Anesth-30)]
The change in BV (∆BV) calculated with each serum
marker was defined as the difference between the ba-
seline BV (Anaesth-30) and the BV at the end of irriga-
tion (Anesth-end). Blood loss was calculated by assaying
Hct and the volume of the discarded irrigation fluid,
using the formula:
Blood Loss (BL) = BV × Hct (of the discarded irriga-
tion fluid)/Hct (Recovery)
WB was calculated by the following formula:
WB = Irrigation (Used) – Irrigation (Discarded) + BL
where, Irrigation (Used) is the amount of irrigation fluid
used and Irrigation (Discarded) is the amount of fluid
discarded. These fluid volumes were exactly measured
using a graduated cylinder (5 L). The fluid used for
irrigation was 3% sorbitol in water (Baxter Ltd., Deer-
field, IL, USA), with an osmolarity of about 165
mOs m·L−1. The irrigation fluid bag was placed at a
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Changes in Blood Volume and Colloid Osmotic Pressure during Fluid Absorption in
Patients Undergoing Endoscopic Urosurgery: An Observational Study
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398
height of 50 cm above the bladder.
All data are expressed as mean  standard deviation
(SD) unless otherwise stated. P < 0.05 was considered to
be significant. The correlations between WB and ∆BV
calculated from Hct, COP, TP and Alb (∆BV-Hct, BV-
COP, V-TP and ∆BV-Alb, respectively) were analyzed
by pearson’s correlation coefficient test. When a signi-
ficant correlation was found, the agreement between WB
and ∆BV was assessed by Bland-Altman analysis.
3. Results
A total of eighty-five patients were recruited for the
study and operated upon. Table 1 summarizes the clini-
cal characteristics of the eighty-five patients included in
the study. Of them, we excluded three patients who had a
high amount of absorption, resulting in hyponatremia, as
they had a large amount of bleeding and required transfu-
sion or colloid administration. The correlations between
WB and ∆BV-Hct, ∆BV-COP, ∆BV-TP and ∆BV-Alb
for the remaining eighty-two patients are shown in Fig-
ure 2. However, as most data showed that WB was close
to zero, indicating that patients had little bleeding and
absorption, patients with WB less than 300 ml were ex-
cluded from the analysis (Excluded area: Dot boxes in
Figure 2).
As a result, 12 patients undergoing TUR-P and 8 pa-
tients undergoing TUR-Bt were selected for further study.
Table 2 summarizes the clinical characteristics of the 20
patients included in the study. The correlations between
WB and ∆BV-COP, ∆BV-TP and ∆BV-Alb except ∆BV-
Hct are shown in Figure 3. There was a significant cor-
relation between WB and ∆BV-COP (R2 = 0.72; P <
0.01), WB and ∆BV-TP (R2 = 0.59; P < 0.01), and WB
and ∆BV-Alb (R2 = 0.57; P < 0.01). On the other hand,
there was no correlation between WB and ∆BV-Hct (R2
= 0.06). Bland–Altman analysis of WB and ∆BV-COP,
∆BV-TP and ∆BV-Alb are shown in Figure 4. Bland-
Altman analysis of WB and ∆BV-COP indicated a bias
of 0.04 with limits of agreement from −0.14 to 0.22, with
agreement in 18 of the 20 pairs of samples (90%). Bland-
Altman analysis of WB and ∆BV-TP indicated a bias of
0.12 with limits of agreement from −0.10 to 0.35, with
agreement in 17 of the 20 pairs of samples (85%). Bland-
Altman analysis of WB and ∆BV-Alb indicated a bias of
0.08 with limits of agreement from −0.08 to 0.25, with
agreement in 16 of the 20 pairs of samples (80%).
Table 1. Data and clinical characteristics of study subjects
(n = 85).
Number of patients n = 85
Age (yr) 68.9  11.2 (33 - 89)
Height (cm) 163.4  7.71 (152 - 180)
Weight (kg) 61.7  9.96 (44 - 90)
Time of operation (min) 101  54.1 (16 - 280)
Blood loss (ml) 43.1  67.1 (0 - 2146)
Irrigation fluid (L) 16.0  1.38 (1.50 - 57.0)
Discarded fluid (L) 15.4  1.34 (1.50 - 56.2)
Water Balance (L) 0.35  0.88 (−0.1 - 1.25)
Weight of the tumor (g) 9.61  17.4 (0 - 55)
BVAllen in the “Awake” state (L) 4.9  0.54 (2.91 - 5.86)
Table 2. Data and clinical characteristics of study subjects
(n = 20).
Number of patients n = 20
Age (yr) 69.0  12.8 (44 - 87)
Height (cm) 167.8  5.1 (158 - 176)
Weight (kg) 64.5  10.2 (48 - 86)
Time of operation (min) 148  64.7 (60 - 280)
Blood loss (ml) 156.0  46 (60 - 446)
Irrigation fluid (L) 29.7  1.93 (10.5 - 57.0)
Discarded fluid (L) 29.2  19.2 (10.0 - 56.2)
Water Balance (L) 0.51  0.20 (0.3 - 1.25)
Weight of tumor (L) 14.9  14.5 (1 - 55)
BVAllen in the “Awake” state (L) 4.74  0.40 (3.56 - 5.86)
Figure 2. Relationships between changes in blood volume during irrigation, calculated from hematocrit (∆BV-Hct), colloid
osmotic pressure (∆BV-COP), total protein (∆BV-TP) and albumin (∆BV-Alb), and water balance (WB) (n = 82). The areas
enclosed in the dot boxes are excluded in Figure 3.

Changes in Blood Volume and Colloid Osmotic Pressure during Fluid Absorption in
Patients Undergoing Endoscopic Urosurgery: An Observational Study
399
Figure 3. Relationships between changes in blood volume during irrigation, calculated from colloid osmotic pressure (∆BV-
COP), total protein (∆BV-TP) and albumin (∆BV-Alb), and water balance (WB) (n = 20).
Figure 4. Bland–Altman bias plot comparing water balance (WB) and changes in blood volume calculated from colloid os-
motic pressure (∆BV-COP), total protein (∆BV-TP) and albumin (∆BV-Alb). The fine lines indicate the 95% confidence in-
terval (CI) and show the limits of agreement, which was 1.96 standard deviation (SD) around the mean difference (bias;
heavy line) (n = 20).
There was an additional margin of error in Bland-
Altman analysis of WB and ∆BV-TP, and WB and ∆BV-
Alb, which indicates that WB is usually bigger than
∆BV-TP and ∆BV-Alb.
4. Discussion
Determining ∆BV is an essential component of perio-
perative fluid management. We used Hct, COP, TP and
Alb as serum markers to estimate plasma dilution, and
verified the accuracy of these parameters in estimating
∆BV. Given the nature of these surgical procedures,
transpiration probably contributed minimally to ∆BV.
The volume of fluid infused intravenously was too small
to account for the increase in BV observed during irri-
gation. All measurements, except those performed in the
“Awake” and “Recovery” state, were performed during
periods of stable anesthesia and hemodynamics. There-
fore, the variation in serum markers from “Anesth-30” to
“Anesth-end” was most likely due to absorption of the
irrigation fluid. Measurement of changes in Hct, COP,
TP and Alb thus appears to be a reliable method for
estimating ∆BV resulting from dilution or concentration
of the blood during the perioperative period. In this study,
we evaluated the accuracy of measuring ∆BV using four
markers and researched the most convenient marker
among them.
A major finding of the present study was that Hct
changed minimally, and ∆BV-COP, ∆BV-TP and ∆BV-
Alb have similar correlation with WB; however, ∆BV-
TP and ∆BV-Alb underestimated WB. We propose se-
veral possible underlying mechanisms to explain these
results.
First, Hct is commonly used for the long-term mana-
gement of patients with chronic diseases and as a marker
of dilution in the therapy of dehydration. However, there
are disputes regarding the validity of using Hct for esti-
mating the state of hydration [8,9]. Some investigators
have shown that there is a difference between the ana-
tomic width of the microvasculature and the dimensions
of the space available for circulating erythrocytes. The
former is termed as the “endothelial surface layer” (ESL)
and the fluid in this area is without erythrocytes and is
either immobile or moves very slowly. However, the vo-
lume of the ESL probably does not remain constant when
plasma is replaced or diluted with artificial fluids. In
such cases, the ESL can dissolve in the flowing blood,
thereby decreasing the thickness of the ESL and wi-
dening the circulating column. This decreases flow resis-
tance and increases microvessel Hct [10,11]. Therefore,
Hct is easily changeable under clinical conditions. From
this viewpoint, Hct is not a reliable dilution marker for
precisely estimating minute changes in BV.
On the other hand, plasma proteins are thought to be
included in the ESL [12,13]. Thus, TP and Alb remain
unaltered by the changing ESL. In this study, ∆BV-TP
and ∆BV-Alb correlated with WB and were constantly
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400
smaller than WB with an additional margin of error in
Bland-Altman analysis. This is because the hypo-osmolar
sorbitol solution that was used for irrigation probably
passed from the intravascular to the extravascular com-
partment. These results indicate that the absorbed irriga-
tion fluid passed through the pores into the intracellular
compartment at a relatively constant rate.
Finally, COP had the greatest correlation with WB.
Considering the leak of absorbed irrigation fluid from the
intravascular to the extravascular space, ∆BV-COP should
have been smaller than WB. However, it did not have an
additional margin of error in Bland-Altman analysis.
Thus, ∆BV-COP was bigger than the “true” BV changes,
indicating that ∆BV-COP may overestimate WB.
COP is determined not only by albumin, but also by
several other kinds of oncotic substances, including sphe-
rical colloids such as glycogen and hydroxyethyl starch,
and linear colloids such as fibrinogen and dextran. As
these colloid molecules are too large to pass through the
pores, they do not usually leak out from the intravascular
to the extravascular space, except in cases of bleeding or
worsening of the patient’s general condition, as with
shock. The mechanism of the overestimation in ∆BV-COP
has not been clarified. However, the fact that only ∆BV-
COP was overestimated implies the presence of large
vascular pores, restricting the passage of TP and Alb, and
permitting the passage of other oncotic substances during
this study. The passage of molecules across pores is more
dependent on their diameter than the weight-average
molecular weight (MWw) [14]. Oncotic substances with
a relatively small radius can easily pass from the intra-
vascular to the extravascular compartment, leading to a
decrease in the concentration of circulating molecules
and resulting in overestimation of BV. If the vascular
pore is extended, there is a possibility that oncotic sub-
stances may leak out from the intravascular to the extra-
vascular space as well.
The endothelial glycocalyx, which normally binds to
large anionic molecules and prevents their extravasation,
is so sensitive that an increase in capillary hydrostatic
pressure caused by volume expansion can result in lea-
kage of larger molecules from the intravascular to the
extravascular space [15]. Since the induction of anesthe-
sia causes a rapid decrease in arterial and capillary
pressures, it creates a mismatch between BV and the in-
travascular space, which could result in some kind of
endothelial change. In this way, if an appreciable number
of macromolecules smaller than TP and Alb, which de-
termine the COP, leak out of the intravascular space for
some reason, the resultant lower COP may be inter-
preted as an increase in BV. Although we cannot explain
how endoscopic urologic surgeries and general anesthe-
sia alter microvascular permeability, capillary leak may
have occurred during the procedure, explaining our re-
sults.
In this study, COP was measured at the patient’s bed-
side using an osmometer, which is a very useful device
of portable size (3.2 kg) that can measure COP in 180 -
300 seconds. Using this device, we could recognize rapid
decreases in COP in three patients and were able to ad-
dress hyponatremia at an early phase. Overestimation
helped us identify even small changes with greater sen-
sitivity. On the other hand, measurements of TP and Alb
required an automated analyzer (BioMajesty JCA-BM-
6050; JEOL, Tokyo, Japan); this analyzer is usually set
up in a large laboratory and cannot be used for simple
measurements in the operating room. Hence, measuring
∆BV-COP may be a more convenient method of estima-
ting WB.
Our study has several limitations. The first limitation
is that we did not control for the influence of anesthesia.
Irrigation was initiated 30 min after the induction of
anesthesia, at which time there was little change in blood
pressure and heart rate. Furthermore, there were minimal
changes in vital signs during irrigation, indicating the ab-
sence of changing anesthetic depth. Hence, we estima-
ted that the influence of anesthesia on the measured va-
riables was minimal. However, the influence of anes-
thesia would have a little effect on the overestimation of
∆BVCOP.
A second limitation is that many patients had little
bleeding and absorption. In the literature, the volume of
blood loss (BL) during endoscopic urologic surgery of
the prostate is estimated to be an average of 693 ml (60
to 2554 ml) [16], which is a large amount of absorption.
In contrast, in our study, the volume of BL and WB were
much smaller than those in this previous study. As seen
in Table 2, the average BL in our study was 156 ml (60 -
446 ml). Further study is therefore necessary to correlate
large changes in WB with ∆BV.
In conclusion, although COP overestimates ∆BV, it is
a useful parameter, which allows quick and easy esti-
mation of WB, especially in situations where there is a
sudden deterioration in the patient’s condition. We also
found that although TP and Alb can accurately estimate
BV than COP, they are not suitable for intraoperative se-
rial measurement. Meanwhile, Hct is not a reliable di-
lution marker for precise estimations of minute changes
in BV. These results indicate that COP is the most sui-
table dilution marker in the perioperative period.
5. Acknowledgments
Assistance with the study: We would like to thank the
concerned anesthesia personnel for general assistance in
support of this study. We also thank Forte Science Com-
munications (Tokyo, Japan) for assistance with the ma-
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nuscript.
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