Continuous Noninvasive Hemoglobin Monitoring

Reflects the Development of Acute Hemodilution

After Consecutive Fluid Challenges
Şerban Ion Bubenek-Turconi, MD,*† Liana Văleanu, PhD,*† Mihai Popescu, MD,*
Eugenia Panaitescu, PhD,‡ Dana Tomescu, MD,* Mihai Cătălin Cacoveanu, PhD,†
and Azriel Perel, MD§

BACKGROUND: Consecutive fluid challenges (FCs) are frequently administered to maximize the
stroke volume (SV) as part of a goal-directed therapy (GDT) strategy. However, fluid administra-
tion may also cause acute hemodilution that might lead to an actual paradoxical decrease in
oxygen delivery (DO2). The aim of this study was to examine whether continuous noninvasive
hemoglobin (SpHb) monitoring can be used to detect the development of acute hemodilution
after graded fluid administration.
METHODS: In 40 patients who underwent major vascular or gastrointestinal surgery, an FC,
consisting of 250 mL colloid solution, was administered. When the SV increased by ≥10%, the
FC was repeated up to a maximum of 3 times. Laboratory-measured hemoglobin concentrations
(BHb), SpHb, SV, cardiac output (CO), and DO2 values were recorded after each FC.
RESULTS: All 40 patients received the first FC, 32 patients received the second FC, and 20
patients received the third FC (total of 750 mL). Out of the 92 administered FCs, only 55 (60%)
caused an increase in SV ≥10% (“responders”). The first and the second FCs were associated
with a significant increase in the mean CO and DO2, while the mean SpHb and BHb decreased
significantly. However, the third and last FC was associated with no statistical difference in CO
and SV, a further significant decrease in mean SpHb and BHb, and a significant decrease in DO2
in these patients. Compared to their baseline values (T0), BHb and SpHb decreased by a mean
of 5.3% ± 4.9% and 4.4% ± 5.2%, respectively, after the first FC (T1; n = 40), by 9.7% ± 8.4%
and 7.9% ± 6.9% after the second FC (T2; n = 32), and by 14.5% ± 6.2% and 14.6% ± 5.7% after
the third FC (T3; n = 20). Concordance rates between the changes in SpHb and in BHb after
the administration of 250, 500, and 750 mL colloids were 83%, 90%, and 100%, respectively.
CONCLUSIONS: Fluid loading aimed at increasing the SV and the DO2 as part of GDT strategy
is associated with acute significant decreases in both BHb and SpHb concentrations. When
the administration of an FC is not followed by a significant increase (≥10%) in the SV, the DO2
decreases significantly due to the development of acute hemodilution. Continuous noninvasive
monitoring of SpHb does not reflect accurately absolute BHb values, but may be reliably used
to detect the development of acute hemodilution especially after the administration of at least
500 mL of colloids.  (Anesth Analg XXX;XXX:00–00)

KEY POINTS
• Question: Does noninvasive continuous monitoring of hemoglobin (SpHb) reflect in real time
the development of acute hemodilution during fluid loading?
• Findings: Fluid challenges (FCs) administered to 40 patients as part of a goal-directed
therapy (GDT) protocol caused a similar significant acute decrease in SpHb and in laboratory-
measured hemoglobin concentrations (BHb), which were associated with a decrease in oxygen
delivery (DO2) when the FC failed to significantly increase the stroke volume (SV).
• Meaning: The development of acute hemodilution during graded fluid loading may eventually
lead to a paradoxical decrease in DO2 and can be reliably followed by continuous monitoring
of SpHb, especially in patients who receive at least 500 mL of colloid solution.

P
erioperative goal-directed therapy (GDT) has been postoperative morbidity and mortality. Although enthusi-
extensively studied and frequently recommended astically promoted for >20 years, the evidence supporting
as a hemodynamic strategy that may decrease the clinical benefit of GDT remains inconclusive1,2 due to

From the *Department of Anesthesiology and Intensive Care, Fundeni Clinic,
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
†1st Department of Cardiovascular Anesthesiology and Intensive Care,
Prof. C.C. Iliescu Institute for Cardiovascular Diseases, Bucharest, Romania;
‡Department of Marketing, Technology and Medical Informatics, Carol
Davila University of Medicine and Pharmacy, Bucharest, Romania; and
§Department of Anesthesiology and Critical Care, Sheba Medical Center, Tel
Aviv University, Tel Aviv, Israel.
Accepted for publication May 30, 2019.
Copyright © 2019 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000004323
Funding: None.
Conflicts of Interest: See Disclosures at the end of the article.
Institutional review board: The study was approved by the local institu-
tional ethics committee (Nr. 19630/20.09.2016). Dr Iulia Daniela Kulscar, MD,
Secretary of the Ethics Committee. Tel: 0040722729948; Fax: 0040213175221;
e-mail: iulia_kulcsar@yahoo.com.
Reprints will not be available from the authors.
Address correspondence to Şerban Ion Bubenek-Turconi, MD, 1st Depart-
ment of Cardiovascular Anesthesiology and Intensive Care, Carol Davila
University of Medicine and Pharmacy, Bucharest 050474, Romania. Address
e-mail to bubenek@alsys.ro.

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 Noninvasive Hemoglobin Monitoring Reflects Hemodilution During Fluid Loading
the negative results of some large randomized controlled
trials,3,4 the overall low quality of GDT trials,1 and the fact
that the term GDT is used interchangeably to describe a
variety of “goals,” protocols, and monitoring modalities.1,5
In general, GDT strategies are based on the preemptive
administration of intravenous (IV) fluids and possibly ino-
tropes to target hemodynamic goals to maximize the stroke
volume (SV), cardiac output (CO), and the oxygen delivery
(DO2).3,4,6 This approach has usually resulted in the GDT
group patients receiving significantly more fluids, specifi-
cally colloids, than the standard care group.3–5,7
One of the unintended and possibly less-appreciated
consequences of such liberal fluid administration is the
development of acute iatrogenic hemodilution.8,9 Such
hemodilution may lead to an actual decrease in DO2, espe-
cially in patients who do not respond to fluid loading by
increasing their CO (“nonresponders”).10,11 In view of the
fact that up to 70% of the fluid challenges (FCs) adminis-
tered during GDT may not produce the expected increase
in SV,7,12 such a paradoxical decrease in DO2 may be more
prevalent than initially thought.
New technological developments in pulse oximetry
have made it possible to monitor hemoglobin (Hb) continu-
ously and noninvasively (SpHb).13,14 SpHb monitoring may,
theoretically, reflect the development of acute hemodilu-
tion during fluid loading in real time.8 We have therefore
designed this study to answer the following questions: (1)
Does fluid administration aimed at increasing the SV cause
acute hemodilution and to what degree? (2) Can this hemo-
dilution lead to a paradoxical decrease in DO2? (3) Can
SpHb monitoring reliably track the development of acute
hemodilution?
METHODS
This prospective clinical study was conducted in the depart-
ment of anesthesiology and intensive care of a tertiary care
university teaching hospital after obtaining institutional
ethics committee approval and written patient consent. The
general inclusion criteria were the following: open major
vascular or gastrointestinal surgery and the intent of the
treating anesthesiologist to monitor CO using a FloTrac
device (Edwards Lifesciences, Irvine, CA) due to medi-
cal indications unrelated to the study. Exclusion criteria
included patients <18 years of age, suspected pregnancy,
refusing consent, nonsinus rhythm, weight >120 kg or
<60 kg, clear evidence of hypervolemia and/or pulmo-
nary edema, myocardial ischemia within the preceding
month, left ventricular ejection fraction (LVEF) <30 %, IV
administration of vasodilator, vasoconstrictor or inotropic
medications before surgery, renal failure requiring dialysis,
baseline Hb <8 g/dL, significant aortic regurgitation, the
presence of any known hemoglobinopathy, or recent dye or
contrast studies.
Forty-five patients were enrolled in the study after
informed written consent. After the application of stan-
dard noninvasive monitoring, venous IV lines, a radial
artery catheter, and a urinary catheter were inserted in the
operating room. A central venous catheter was inserted via
the internal jugular vein. Both the arterial and the central
venous pressure transducers were zeroed at the level of
the left atrium. The arterial line was connected to a FloTrac
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sensor (Edwards Lifesciences) and a Vigileo monitor
(Edwards Lifesciences; software version 4.02), which was
used to measure and display in a continuous manner the SV,
the CO, and other hemodynamic parameters not included
in the present study. The opposite index finger was con-
nected to a Masimo adult adhesive sensor (R2-25a) for the
Root Platform containing a Radical-7 Pulse CO-oximeter
(software version 1.5.9.3i; Masimo Corporation, Irvine, CA)
to continuously measure SpHb, the perfusion index (PI),
and the oxygen saturation (Spo2). A dark color shield cov-
ered the Masimo sensor to avoid optical interferences dur-
ing the study period and to minimize heat loss.
General anesthesia was induced with fentanyl 7 µg·kg−1,
midazolam 0.1 mg·kg−1, and atracurium 0.6 mg·kg−1. General
anesthesia was maintained with sevoflurane (titrated to a
minimal anesthetic concentration (MAC) of 0.8–1.2 and a
bispectral index (BIS) value of 40–60), fentanyl, and atracu-
rium as needed. Mechanical ventilation was instituted in a
volume-controlled mode to achieve an end-tidal CO2 value
between 30 and 35 mm Hg. A maintenance fluid adminis-
tration of either 5% dextrose or Ringer solution (at the dis-
cretion of the treating physician) at 1 mL·kg·h−1 was set for
the whole intraoperative period. According to local proto-
cols, all patients received standard measures to maintain
oxygenation (Spo2 ≥94%), laboratory-measured Hb (BHb)
>7.5 g/dL, core temperature ≥36°C, mean arterial pressure
(MAP) of 60–100 mm Hg, and heart rate (HR) ≤100/min.
After the induction of general anesthesia and before the
start of surgery, when the patients were hemodynamically
stable, HR, MAP, SV, CO, and Spo2 values were recorded
(baseline values [T0]). If the PI value was ≥1.0, the SpHb
value on the Masimo platform was recorded and an arte-
rial blood sample was drawn and sent to the laboratory for
BHb measurement by a CO-oximeter (model ABL 800flex;
Radiometer, Copenhagen, Denmark). The blood sample
included 2 mL and was drawn by a dedicated heparinized
syringe after 10 mL of arterial blood with heparinized saline
(“dead space”) was drawn from the arterial catheter. To
minimize unnecessary blood loss, the initial 10 mL of blood
and heparinized saline mixture was returned to the patient.
A GDT strategy was then applied in all patients to maxi-
mize SV by fluid administration. The protocol included
the administration of an FC of 250 mL colloid solution
(Gelofusine 4 g/100 mL; B. Braun, Melsungen, Germany)
over 1 minute and, after 5 more minutes, the measurement
of all the variables described above (after the first FC [250
mL colloid solution]; T1). This procedure was repeated once
(after the second FC [T2]) or twice (after the third FC [T3]) as
long as the SV measured after the FC increased by ≥10%. All
data were recorded in our patient data management system
(HIM-GmbH, Bad Homburg, Germany) for further review
and analysis. DO2 values were calculated offline using the
formula: DO2 = arterial oxygen content (Cao2) × CO, where
Cao2 = (Hb × 1.38 × Spo2) + (partial pressure of oxygen
[Pao2] × 0.0031). BHb and Pao2 values from the same arte-
rial blood samples were used to calculate the Cao2 values.
Statistical Analysis
Continuous variables, including SpHb, BHb, CO, and DO2,
were tested for normality using the Shapiro–Wilk test. The
Student t test for paired samples was used for normally
ANESTHESIA & ANALGESIA

distributed variables, and the Wilcoxon signed-rank test
was used for variables with abnormal distribution. Data
are presented as mean ± standard deviation (SD). In those
patients in whom all 3 FCs were administered (a total col-
loid volume of 750 mL), a Mauchly test was applied, fol-
lowed by an analysis of variance (ANOVA) test for repeated
measures and a Bonferroni post hoc test for all the continu-
ous variables that were studied. The changes in Hb concen-
trations and hemodynamics before and after the last FC in
all 40 patients were also calculated.
To assess the ability of the changes in SpHb to track the
changes in BHb, we used 4-quadrant plots, which deter-
mine trending ability and the directionality of change. The
concordance rate is the percentage of data points in which
the direction of change in Hb measured by the 2 devices is
in agreement. To eliminate the less-predictive data points
that lie near the center of the plot, we applied an arbitrary
exclusion zone of 5% (0.6 g·dL−1) and considered values
≥90% of concordance rate to indicate reliable trending abil-
ity. Linear regression analysis was used to test correlations
between simultaneous paired SpHb and BHb values for all
points of the study and correlation coefficients (r) and con-
fidence intervals (95% CIs) were calculated. SpHb accuracy
was assessed using a modified Bland–Altman analysis cor-
rected for multiple measurements for comparison of SpHb
and BHb values at different points of the study and all val-
ues together. The bias (mean absolute difference), precision
(1 SD of the bias), and limits of agreement (LOAs) were cal-
culated and corrected for repeated measurements. For all
measurements, a P value <.05 was considered significant.
We performed a power analysis based on the results of
a previous study10 that showed that a 500 mL fluid bolus is
expected to produce an acute decrease of 8% ± 4% (about 1
g/dL) in the Hb concentration. Assuming an α error of .05
and a power of 0.8, a sample of 20 patients will be needed for
an effect size of 0.7. However, only about 50% of the patients
are expected to be “responders” T17,12 and hence receive at
least 1 more FC (a total of 500 mL) according to our study
protocol; we assumed that at least 40 patients were needed.
We eventually decided to enroll 45 patients taking into con-
sideration a few possible dropouts.
The statistical analysis was performed using Excel
(Microsoft, Redmond, WA) and SPSS version 15.0 statistical
package (SPSS, Chicago, IL).
RESULTS
We enrolled 45 patients in this study. Five patients were
excluded from the final analysis because 2 needed vaso-
constrictor administration for severe hypotension, and in
the other 3, the PI value was <1.0 after the first FC. Patients
characteristics and operative data are presented in Table 1.
Of the 40 patients who received the first FC (T1), 8 patients
had an SV change of <10% (“nonresponders”), so that only
32 patients received the second FC. Twelve of these patients
had an SV change of <10% after the second FC, so that only
20 patients received the third and final FC. In summary, we
studied 40 patients at T0, 40 patients at T1, 32 patients at T2,
and 20 patients at T3.
Out of the 92 administered FCs, 55 (60%) were associ-
ated with an increase in SV ≥10% (“responders”) and
37 (40%) were followed by a change in SV of <10%
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Table 1.  Patient Characteristics and Operative
Data (n = 40)
Female, n (%) 12 (30)
Age, y (mean ± SD) 64 ± 7
Weight, kg (mean ± SD) 78.6 ± 12.1
Height, cm (mean ± SD) 171.9 ± 4.7
BMI, kg/m2 (mean ± SD) 26.5 ± 3.9
BSA, m2 (mean ± SD) 1.9 ± 0.1
ASA I/II/III, n (%) 3 (7.5)/26 (65)/11 (27.5)
Major vascular surgery, n (%) 25 (62.5)
Major intestinal surgery, n (%) 15 (37.5)
Arterial hypertension, n (%) 32 (80)
Coronary disease, n (%) 24 (60)
COPD, n (%) 24 (60)
Renal failure, n (%) 14 (47.5)
Nonsinus rhythm, n (%) 0 (0)
Vasopressors, n (%) 0 (0)
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass
index; COPD, chronic obstructive pulmonary disease; SD, standard deviation.
(“nonresponders”). At each time point, and irrespective
of the number of administered FCs, fluid administration
induced a significant increase in mean CO and in DO2 and
a significant decrease in SpHb and BHb compared to their
T0 (Table 2). BHb and SpHb decreased by a mean of 5.3% ±
4.9% and 4.4% ± 5.2%, respectively, T1 (n = 40), by 9.7% ±
8.4% and 7.9% ± 6.9% T2 (n = 32), and by 14.5% ± 6.2%, and
14.6% ± 5.7% T3 (n = 20).
The mean CO, DO2, and Hb values at each time point are
shown in Figure 1. T3, the mean CO remained statistically
unchanged, with 17 (85%) of the 20 patients being “non-
responders,” while the mean DO2 decreased significantly.
Similarly, the last fluid bolus that each of the 40 patients
received was associated with a significant decrease of both
SpHb and BHb values, no significant change in CO, and a
significant decrease in the mean DO2 value (Table 3).
A scatter plot of all 132 paired values of SpHb and BHb is
shown in Figure 2. Linear regression analysis showed only
a moderate positive correlation between SpHb and BHb for
all 132 paired of measurements: the correlation coefficient r
was 0.58 and the 95% CI was 0.46–0.68. Bland–Altman anal-
ysis of all 132 paired SpHb and BHb values, corrected for
multiple measurements, showed both low mean bias and
precision values of −0.3 ± 1.5 g/dL and wide LOAs of −2.7
to 3.3 g/dL (Figure 2).
An excellent concordance rate of 100% (19 of 19 points
in the same direction outside the exclusion zone of 5%)
with 95% CI (83%–100%) was found between the changes
in SpHb and in BHb after the administration of 750 mL
(Figure 3). A lesser yet acceptable concordance rate of 90%
(28 of 31 points in the same direction outside the exclusion
zone of 5%) with 95% CI (75%–97%) was found between the
changes in SpHb and in BHb after the administration of 500
mL. The concordance rate between the changes in SpHb
and in BHb after the administration of 250 mL was found
to be only 83% (26 of 31 points in the same direction outside
the exclusion zone of 5%) with 95% CI (67%–92%).
DISCUSSION
The main results of our study show that graded fluid load-
ing aimed at increasing the SV as part of a GDT strategy
is associated with a significant gradual decrease in Hb
 Noninvasive Hemoglobin Monitoring Reflects Hemodilution During Fluid Loading

Table 2.  Changes in Hemodynamics and Hemoglobin Concentrations in All Patients Compared With T0
Mean Change (%) (95% CI) P Value
T0–T1 (40 patients) T0 T1
  SpHb (g·dL−1) 12.1 ± 1.3 11.6 ± 1.6 −4.4 ± 5.2 (−6.0 to −2.6) <.001a
  BHb (g·dL−1) 11.9 ± 1.7 11.3 ± 1.5 −5.3 ± 4.9 (−6.8 to −3.7) <.001a
  CO (L·min−1) 4.0 ± 0.8 4.5 ± 0.9 13.3 ± 16.9 (7.9 to 18.7) <.001a
 DO2 (mL·min−1) 686 ± 171 729 ± 152 8.1 ± 16.9 (2.7 to 13.5) .006a
T0–T2 (32 patients) T0 T2
  SpHb (g·dL−1) 12.1 ± 1.1 11.2 ± 1.4 −7.9 ± 6.9 (−10.3 to −5.3) <.001a
  BHb (g·dL−1) 11.9 ± 1.8 10.7 ± 1.5 −9.7 ± 8.4 (−12.7 to −6.6) <.001a
  CO (L·min−1) 4.0 ± 0.9 5.3 ± 1.0 35.6 ± 21.4 (27.9 to 43.3) <.001a
 DO2 (mL·min−1) 678 ± 168 822 ± 195 23.4 ± 25.8 (14.0 to 32.7) <.001a
T0–T3 (20 patients) T0 T3
  SpHb (g·dL−1) 11.9 ± 1.2 10.1 ± 1.3 −14.6 ± 5.7 (−17.2 to −11.9) <.001a
  BHb (g·dL−1) 11.9 ± 1.6 10.2 ± 1.5 −14.5 ± 6.2 (−17.3 to −11.5) <.001a
  CO (L·min−1) 3.8 ± 0.8 5.1 ± 0.9 35.5 ± 23.4 (24.5 to 46.5) <.001a
 DO2 (mL·min−1) 649 ± 130 748 ± 155 17.0 ± 24.1 (5.7 to 28.2) .002a
Data are expressed as mean ± SD.
Abbreviations: BHb, laboratory hemoglobin; CI, confidence interval; CO, cardiac output; DO2, oxygen delivery; SD, standard deviation; SpHb, continuous noninvasive
hemoglobin; T0, baseline values; T1, after first FC (250 mL colloid solution); T2, after second FC; T3, after third FC.
a
Significant difference compared with T0 values.

Figure 1. The effects of graded fluid loading on the SpHb and BHb concentrations, CO, and DO2 in all patients. Data are presented as mean
± SD at each time point of the study. *Significant difference (P < .05) compared to the preceding time point. Note significant decrease in
DO2 after the third FC (T3). BHb indicates laboratory hemoglobin; CO, cardiac output; DO2, oxygen delivery; FC, fluid challenge; SD, standard
deviation; SpHb, continuous noninvasive hemoglobin; T0, baseline values; T1, after the first FC (250 mL colloid solution); T2, after the second
FC; T3, after the third FC.

Table 3.  Changes in Hemodynamics and in Hemoglobin Concentration Before and After the Last Fluid Bolus
That Was Administered to All 40 Patients (8 Patients T0–T1, 12 Patients T1–T2, 20 Patients T2–T3)
Before After Mean Change (%) (95% CI) P Value
SpHb (g·dL−1) 11.5 ± 1.6 11.0 ± 1.8 −4.5% (−5.9% to −2.8%) <.001a
BHb (g·dL−1) 11.2 ± 1.6 10.4 ± 1.5 −6.5% (−8.3% to −4.6%) <.001a
CO (L·min−1) 4.9 ± 1.0 4.9 ± 1.0 −0.1% (−4.3% to 3.9%) .83
DO2 (L·min−1) 802 ± 183 746 ± 167 −5.7% (−10.5% to −0.9%) .001a
Data are expressed as mean ± SD.
Abbreviations: BHb, laboratory hemoglobin; CI, confidence interval; CO, cardiac output; DO2, oxygen delivery; SD, standard deviation; SpHb, continuous noninvasive
hemoglobin; T0, baseline values; T1, after first FC (250 mL colloid solution); T2, after second FC; T3, after third FC.
a
Significant difference.

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Figure 2. A, A scatter plot of 132 paired measurements as determined by BHb and by SpHb. SpHb and BHb are expressed as g/dL. The cor-
relation coefficient (r) was 0.58, and the 95% confidence interval was 0.46–0.68. B, Corrected Bland–Altman plot for repeated measurements
of 132 paired hemoglobin values as determined by BHb and by SpHb. The dashed black line represents the mean bias (−0.3 g·dL−1), the
dashed blue lines represent 1 SD (1.5 g·dL−1), and the continuous black lines represent the LOA (−2.7 to 3.3 g·dL−1). BHb indicates laboratory
hemoglobin; LOA, limit of agreement; SD, standard deviation; SpHb, continuous noninvasive hemoglobin.

Figure 3. A 4-quadrant scatter plot of the changes in SpHb and in BHb concentrations after the administration of 750 mL of colloids (T0–T3,
n = 20). The concordance rate between changes in SpHb and BHb is 100% (95% confidence interval, 83%–100%) with an exclusion zone of
5%. BHb indicates laboratory hemoglobin; FC, fluid challenge; SpHb, continuous noninvasive hemoglobin; T0, baseline values; T3, after the
third FC.

concentrations. The development of this acute hemodilution
is associated with a significant decrease in the DO2 when
FCs fail to significantly increase the SV in “nonresponders.”
Although the ability of absolute SpHb values to reflect BHb
is limited, SpHb can be clinically used to reliably track
changes in BHb when >500 mL of colloids is administered.
The correct strategy for perioperative fluid administra-
tion has been a topic of constant debate and controversy.
Its importance stems from the recognition that too “lib-
eral” and too “restrictive” intraoperative fluid dosing are
associated with increased morbidity, mortality, cost, and
length of stay.15 Perioperative IV fluid administration that is

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 Noninvasive Hemoglobin Monitoring Reflects Hemodilution During Fluid Loading
guided by CO monitoring as part of a hemodynamic GDT
algorithm has been promoted as a mean to reduce postop-
erative complications by improving tissue perfusion and
oxygenation in high-risk surgical patients.3,4,6,7 This GDT
strategy is usually achieved by the administration of 250
mL boluses of IV colloid solution that are repeated as long
as the SV keeps increasing by at least 10% of its prebolus
value or when a decrease >10% in the SV is observed.3,4,6,7
We have used this GDT protocol in our study to examine its
acute impact on the Hb concentration, because one of the
potentially detrimental yet less-appreciated effects of exces-
sive fluid administration is the development of acute iatro-
genic hemodilution.8,9 The degree of hemodilution has been
shown to be more significant after the administration of col-
loids compared to crystalloids.16,17 The results of our study
clearly show that the administration of colloid FCs causes
a consistent acute decrease in the Hb. The administration
of 250 mL colloids led to a small yet highly significant and
consistent acute decrease of about 5% in the mean Hb val-
ues, while 750 mL colloids were associated with a decrease
of about 15% (1.7 g/dL in our patient population) compared
to baseline Hb values. This degree of acute hemodilution
is in the same range observed in previous studies done in
healthy volunteers16,17 and in critically ill patients.10
The findings of our study have potential clinically
important implications. The first one is that fluid loading
may often cause an unexpected decrease in the DO2, as
has been previously observed in critically ill and in sur-
gical patients.10,11,18 It is safe to assume that such a para-
doxical decrease in DO2 due to hemodilution occurs quite
frequently, because >50% of the FCs administered as part
of GDT protocol have been reported to have no significant
effect on the SV.7,12 This realization should prompt us to
reconsider the definition of “fluid responsiveness” which is
based solely on the response of the CO or the SV to an FC.
Our results clearly show that a “nonresponder” is not a neu-
tral term and that a lack of increase in the SV after an FC is
in fact inherently associated with an acute decrease in DO2
due to the associated hemodilution. Hemodilution may also
decrease the DO2 at the microcirculatory level, lead to organ
and tissue hypoxia, and contribute significantly to the detri-
mental effects of fluid overload.9,19
The detection of the development of hemodilution
after fluid administration may therefore be of great clini-
cal importance. However, when Hb levels are measured
intermittently and with long intervals between measure-
ments, changes in Hb may be delayed or missed alto-
gether.14 Our study attempted to examine whether the
continuous, noninvasive monitoring of SpHb may detect
the development of hemodilution in real time. However,
the accuracy of SpHb and especially its ability to guide
clinicians to make transfusion decisions has been repeat-
edly challenged. A meta-analysis including 32 studies con-
cluded that despite a small bias and SD of 0.10 ± 1.37 g/
dL found between noninvasive SpHb measurements and
invasive central laboratory-measured BHb, the observed
wide LOAs (−2.59 to 2.80 g/dL) should make clinicians
wary of making clinical decisions based on the absolute
values of SpHb.20 Our results also show that although the
mean bias (SD) between SpHb and BHb was small −0.3 g/
dL (±1.5 g/dL), the LOAs were wide (−2.7 to 3.3 g/dL)
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reaffirming the poor accuracy of absolute SpHb values in
reflecting the absolute BHb values. These results are in line
with those of other studies, which were also performed
in surgical patients and which compared absolute SpHb
values measured by Radical-7 Pulse CO-oximeter with
the absolute BHb values measured by the same laboratory
CO-oximeter that was used in our study.21,22
Despite the limited accuracy of the SpHb to reflect
absolute BHb values, our study shows that SpHb values
decreased significantly and consistently after each FC. More
importantly, we observed an excellent concordance rate of
100% between changes in SpHb and in BHb after the admin-
istration of 750 mL colloids and a lesser yet acceptable con-
cordance rate of 90% after the administration of 500 mL. Of
note, these results may have been negatively affected by the
well-recognized inherent variability of the laboratory Hb
device that served as our reference method.14
These findings demonstrate that the monitoring of SpHb
may have potential clinical benefits beyond the detection of
actual bleeding. A decrease in the SpHb in the absence of
bleeding in an acutely ill patient may be the only sign of
hemodilution and should prompt an immediate revision of
the fluid administration strategy. The real-time identifica-
tion of hemodilution may also have an important potential
impact on the decisions to transfuse blood, especially when
the Hb values decrease to a level below the acceptable trans-
fusion threshold.4,8,23,24 Of note, the multitude of studies that
have examined the possible clinical benefit of restrictive
blood management strategies have all been based on spe-
cific Hb values as transfusion thresholds and have not taken
the possibility of hemodilution into account.25–27 Finally, it
has to be noted that the calculation of the estimated intraop-
erative blood loss, which is based on the preoperative and
the postoperative hematocrit values,28 may be unreliable in
the presence of significant hemodilution.
Our study has a number of significant limitations. The
first one is that CO measurement with the FloTrac may be
inaccurate, especially during changes in vascular tone.28
However, no patient in our study received any vasoconstric-
tors during the study period, and all measurements were
done at a steady state before the start of surgery. This device
has been shown to perform reasonably well during fluid
administration.28 Second, in this small study, we have mea-
sured only the acute changes in Hb concentrations after the
FCs and have not followed them throughout surgery and
in the postoperative period. However, we have measured
the Hb values at the same time that the CO is usually mea-
sured after an FC for the determination of fluid responsive-
ness. The dissipation of the hemodilution effect of a single
FC may therefore be similar to the dissipation of the impact
of a single FC on the CO. In the clinical setting, the dura-
tion of the observed acute hemodilution will depend on the
rate of exit of the fluids from the intravascular space and on
the amount, type, and rate of further fluid administration.29
Because many GDT strategies recommend that colloids be
administered as long as the SV increase by >10% or when
the SV decrease by 10%,3,4,6,7 it may well be that the associ-
ated iatrogenic hemodilution may persist or even worsen
throughout the implementation of the GDT strategy.
In summary, our study shows that acute iatrogenic hemo-
dilution does invariably occur after fluid administration
ANESTHESIA & ANALGESIA

that it may lead to paradoxical decrease in DO2 especially in
“nonresponders” and that its development is made visible
by the continuous monitoring of SpHb when >500 mL of
colloids are being administered. Further studies are needed
to examine the potential clinical benefit of SpHb monitoring
in identifying acute hemodilution. E
DISCLOSURES
Name: Şerban Ion Bubenek-Turconi, MD.
Contribution: This author helped propose and initiate the study
design, lead the study, oversee the data collection, and contribute
to the data analysis and manuscript preparation.
Conflicts of Interest: None.
Name: Liana Văleanu, PhD.
Contribution: This author helped supervise the data collection in
vascular patients, analyze the data, and she is the archival author.
Conflicts of Interest: None.
Name: Mihai Popescu, MD.
Contribution: This author helped participate the data collection
and data analysis.
Conflicts of Interest: None.
Name: Eugenia Panaitescu, PhD.
Contribution: This author helped build the data basis of the study
and contribute in a decisive manner in the statistical analysis.
Conflicts of Interest: None.
Name: Dana Tomescu, MD.
Contribution: This author helped participate the data collection
and data analysis.
Conflicts of Interest: None.
Name: Mihai Cătălin Cacoveanu, PhD.
Contribution: This author helped participate the data collection.
Conflicts of Interest: None.
Name: Azriel Perel, MD.
Contribution: This author helped design the study and prepare the
manuscript.
Conflicts of Interest: A. Perel serves as an independent consultant
to Masimo Inc, Irvine, CA.
This manuscript was handled by: Tong J. Gan, MD.
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