Blood Management

Section Editor: Marisa B. Marques

Determination of Perioperative Blood Loss:

Accuracy or Approximation?
A. Lopez-Picado, Pharm,*† A. Albinarrate, MD,†‡ and Borja Barrachina, MD†‡

BACKGROUND: Various different interventions can be used to reduce surgical blood loss;
however, there is no “gold standard” for accurately measuring the volume of perioperative blood
loss, and this makes it difficult to assess the efficacy of these interventions.
METHODS: We used data from a previous multicenter double-blind randomized clinical trial in
patients undergoing total hip arthroplasty in which we compared 2 regimens for administering
tranexamic acid versus placebo. We assessed direct measures (external blood loss) and indirect
estimates (using the formulas of Bourke, Gross, Mercuriali, and Camarasa and a new formula we
have developed) using analysis of variance to compare estimated volumes of blood loss among
the study groups. In addition, intraclass correlation coefficients (ICCs) and Bland–Altman dia-
grams were used to compare the estimated volumes of blood loss obtained with each formula.
RESULTS: The mean estimated external blood loss was 909 ± 324 mL, and the mean esti-
mates of blood loss calculated using the formulas of Gross, Bourke and Smith, and Camarasa
were 1308 ± 555, 1091 ± 454, and 1641 ± 945 mL, respectively, whereas we obtained a value
of 1511 ± 919 mL with the new formula at day 2. In all cases, the results favored the use of
tranexamic acid (P < .0001). Comparing results of the new and other formulas, we found mod-
erate-to-low agreement (in terms of ICCs) except for that of Camarasa (ICC: 0.992). The limits
of agreement with the new formula ranged from −378 to 93 in the case of the comparison with
Camarasa’s formula and from −2226 to 959 for external blood loss, the difference depending
on the magnitude of the estimate to a large extent.
CONCLUSIONS: Formulas that take into account both anthropometric and laboratory parameters
are useful for evaluating the efficacy of interventions aiming to decrease blood loss but do not
ensure that the values obtained are sufficiently accurate for absolute measuring. (Anesth Analg
2017;125:280–6)

T
otal hip and knee replacement surgery are becom-
ing increasingly common in our setting and usu-
ally require both autologous and homologous blood
transfusions1–7 as a result of the high level of blood loss.8–12
Numerous strategies for reducing perioperative surgi-
cal blood loss have been proposed to reduce the number
of transfusions.13–15 Their use is based on the findings of
various clinical trials and meta-analyses16–18 of the main
objective of which was often to compare the blood loss
measured. Surprisingly, these studies propose a wide range
of measurement types and methods for determining this
blood loss, ranging from direct quantification methods to
complex formulas based on anthropometric data and labo-
ratory parameters.
The main reason for this situation is that there is currently
no “gold standard” method for accurately measuring blood
From the *Araba Research Unit, Araba University Hospital, Vitoria-Gasteiz,
Spain; †Bioaraba Research Institute, Vitoria-Gasteiz, Spain; and ‡Department
of Anaesthesia & Perioperative Care, Araba University Hospital, Vitoria-
Gasteiz, Spain.
Accepted for publication January 30, 2017.
Funding: None.
The authors declare no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s website (www.anesthesia-analgesia.org).
Reprints will not be available from the authors.
Address correspondence to Borja Barrachina, MD, Servicio de Anestesiología
y Reanimación, Hospital Universitario de Araba-Sede Txagorritxu, c/ Jose
Atxotegui s/n, 01009 Vitoria-Gasteiz, Spain. Address e-mail to borjabarra@
gmail.com.
Copyright © 2017 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000001992
loss during surgery. There appears to be some degree of
consensus that measurements of external blood loss (quan-
tification of blood volumes present in surgical drains and
pads) do not provide an accurate indication of blood loss as
a result of the significant volume of blood retained in tissues
(occult blood) and difficulties in accurately quantifying the
exact volume of blood contained in dressings and drains.
Nevertheless, despite the aforementioned limitations, vari-
ous studies have used external blood loss as a primary or
secondary end point.19–22
In an effort to find a more accurate measure, it has been
proposed that formulas can be used to determine blood
loss. The literature contains a seemingly endless number of
formulas, and so far, none of them have achieved the status
of reference formula for this type of calculation. This means
that the choice of formula may affect the results of a study
and, therefore, the conclusions and effect of these results on
standard clinical practice.
For this reason, the objective of this study was to assess
whether the results of a previous clinical trial23 are robust to
the use of alternative formulas and compare the estimates
obtained by different blood loss calculation methods.
METHODS
To compare a set of different formulas found in the literature,
we used data obtained during a previous multicenter pla-
cebo-controlled double-blind, parallel-group randomized
clinical trial conducted by this research group,23 in which
blood loss was evaluated in patients undergoing unilateral,
bicompartmental, primary, noncemented, posterolateral,
or anterolateral total hip replacement as a result of osteo-
arthritis. This study had 3 groups: a group that received a

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 single 15-mg/kg dose of tranexamic acid before the start of
surgery, a second group that received two 10-mg/kg doses
(1 before surgery and the other 3 hours after the first dose),
and a third group that received placebo.
The clinical trial was approved by the appropriate insti-
tutional review board, and written informed consent was
obtained from all subjects, a legal surrogate, the parents, or
legal guardians for minor subjects, or the requirement for
written informed consent was waived by the institutional
review board. The study was registered at clinicaltrial.gov
(NCT01199627; Principal Investigator: Borja Barrachina;
February 2013).
Description of the Determination of External
Blood Loss and Formulas Used
External Blood Loss. The assessment of external blood
loss was based on intraoperative blood loss and the
volume of blood obtained from drains up to 48 hours after
completion of the intervention or until withdrawal thereof.
To determine intraoperative blood loss, the volume drained
into aspiration systems and weight of gauzes used were
calculated, subtracting the weight of the dry gauzes and
volume of saline solution used for irrigation.
Formulas for Determining Blood Volume. To be able to
perform this study, a literature review was performed
to identify different formulas that have been proposed.
Of these, the authors agreed to select for our study those
that seem to be used most frequently based on how many
studies in which they had been used were retrieved in
the literature review (see Supplemental Digital Content,
Appendix, http://links.lww.com/AA/B695).
All calculation formulas require an estimation of the total
blood volume of the patient. Hence, we briefly describe the
different methods available for estimating an individual’s
total blood volume and the overall calculation of the vol-
ume of blood loss (which necessarily requires the use of 1
of these methods):
A. Estimation of total blood volume of the patient:
i. Moore’s formula24: the weight, build, and sex of
the patient are taken into account when estimat-
ing total blood volume.
ii. Nadler’s formula25: similarly, the weight, height,
and sex of the patient are used in the calculation.
iii. 
International Council for Standardization in
Haematology26 (ICSH): this formula uses the
body surface area and sex of the patient in the
calculation.
B. Estimation of blood loss:
i. Bourke and Smith27: this proposal is a variation of
a previous proposal from Ward et al28 but avoids
the use of the Naperian logarithm, performing
the approximation using the product of 3 minus
the mean hematocrit value. The total blood vol-
ume of the patient is estimated using the formula
of Nadler et al.25
ii. Gross29: starting from the formulas proposed pre-
viously by Bourke and Smith30 and Ward,31 the
formula is simplified by estimating blood loss on
the basis of the initial hematocrit, final hemato-
crit, and the mean of these 2 values. The volumes
July 2017 • Volume 125 • Number 1
Copyright © 2017 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
transfused are not taken into account. It proposes
the use of Moore’s formula29 to calculate the total
blood volume of the patient.
iii. Mercuriali30: this method uses the hematocrit val-
ues preoperatively and at 5 days postoperatively,
assuming that the patient exhibits the lowest
hematocrit value on that day, and only estimates
the volume of red cells.31 It takes into account the
volume of blood transfused but without distin-
guishing between autologous and homologous
blood. The total blood volume of the patient is
estimated using Nadler’s formula.27
iv. Camarasa (2006)32: this formula also estimates blood
loss on the basis of hematocrit using the preoperative
value together with that at the time when perform-
ing the estimation. It also takes into consideration
the transfusions performed. In contrast to previous
proposals, Camarasa et al32 differentiate between
autologous and homologous transfusions and those
from blood recovery systems. The total blood vol-
ume of the patient is estimated using a simplified
version of the formula proposed by Moore29 consid-
ering only the weight and sex of the patient.
Formulas Chosen for the Comparison in This Study. Because
the formula proposed by Camarasa et al32 takes into account
both the initial and final hematocrit values and the volume
of blood transfused (homologous, autologous, or recovered)
to estimate blood loss, we chose this formula as a reference
for comparison with each of the others.
In addition, we performed comparisons with a modi-
fied version of Camarasa’s proposal, namely, the same for-
mula but calculating the total blood volume of the patient
using the method proposed by the ICSH. Our goal was to
determine whether an a priori, and in the opinion of the
authors of this study, a more accurate method for calculat-
ing this volume had any effect on the results (here on this
modified version of the formula is referred to as the “new
formula”).
To estimate the volume of blood loss, values were calcu-
lated for during surgery and 2 and 4 days postoperatively.
This information was used to apply the 5 formulas described
(namely, those of Bourke and Smith, Gross, Mercuriali,
Camarasa, and the new formula proposed by our group). In
addition, we calculated the external blood loss for each period.
Statistical Analysis
Quantitative variables were described using the mean and
standard deviation, whereas frequency, percentage, and
95% confidence interval were used for qualitative variables.
Parametric analysis of variance was used to compare the
volumes obtained for each group.
The intraclass correlation coefficient (ICC) was used to
assess the agreement between the different formulas stud-
ied. To facilitate interpretation of the data, values of 0.75
or higher were considered to be indicative of an excellent
agreement, values between 0.4 and 0.75 were considered to
be fair to good, and values lower than 0.4 to indicate poor
agreement, as established by other authors.33 In addition,
the method proposed by Bland and Altman was used for
visual analysis of the data.
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 Determination of Perioperative Blood Loss
Ethical Considerations. The study was approved by the
Clinical Research Ethics Committee of the Basque Country
and Navarra and by the Spanish Agency for Medicinal
Products and Medical Devices (AEMPS) and registered with
both EudraCT (EudraCT 2010-021497-11) and clinicaltrials.
gov (reference NCT01199627).
RESULTS
Analysis of the baseline characteristics of the patients
detected no statistically significant differences among the 3
groups for any of the variables studied.
Results of the Clinical Trial Using the Different
Formulas
The Table shows the results of the study as a function of
the formula used. In the case of the formula we propose,
the estimated volumes of blood loss for day 2 after surgery
were 1264 ± 684, 1188 ± 621, and 2066 ±1105 mL for the sin-
gle-dose, two-dose, and placebo groups, respectively, and
those for 4 days after surgery were 1323 ± 691, 1415 ± 958,
and 1576 ± 927 mL for the single-dose, two-dose, and pla-
cebo groups, respectively.
Notably, the differences among the 3 groups (single-
dose, two-dose, and placebo groups) were statistically sig-
nificant regardless of the formula used for estimating blood
loss, except in the case of Gross’s formula at 4 days after
surgery (P = .47). On the other hand, the mean volumes
of blood loss varied markedly depending on the formula
selected, the estimate of blood loss for patients in the control
group being 2215 ± 1136 and 2066 ± 1105 mL when using
Camarasa’s and the new formula, respectively, but only
1309 ± 555 mL according to Gross’ formula.
Differences in total blood volume calculated using the 3
formulas considered were not significant. Specifically, with
Nadler’s formula, the values of total blood volume were cal-
culated to be 4378 ± 732, 4512 ± 688, and 4377 ± 655 mL for
the single-dose, two-dose, and placebo groups, respectively
(P = .644). Using the ICSH formula, the values obtained were
4381 ± 712, 4519 ± 678, and 4408 ± 614 mL for the single-
dose, two-dose, and placebo groups, respectively (P = .659).
Finally, using Moore’s formula, the estimated total blood vol-
umes were 4982 ± 1000, 5064 ± 854, and 4906 ± 904 mL for
the single-dose, two-dose, and placebo groups, respectively
(P = .766).
With regard to the intermeasurement correlations, a
strong and statistically significant correlation was found
among the formulas (P < .0001 in all cases for the results at
day 2 after surgery and P < .05 for day 4 after surgery, except
in the case of Gross’ formula). There was also a strong cor-
relation between the estimate from Nadler’s formula and
that of the ICSH (ICC = 0.983, 95% confidence interval [CI],
0.975–0.988) and between Nadler’s and Moore’s formulas
(ICC = 0.913, 95% CI, 0.874–0.940). The correlation between
the estimates using the ICSH formula and that of Moore
was also high (ICC = 0.863, 95% CI, 0.805–0.905).
Comparison of Blood Loss Estimates Obtained
with the Different Formulas
Day 2. The Table and Figure 1 present our evaluation of
the agreement between the most commonly used formulas
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and the formula we propose (the new formula). In general,
a fair to good correlation was observed in the case of the
formulas of Gross and of Bourke and Smith (ICC = 0.593
and 0.472, respectively), whereas the correlation was poor
in the case of external blood loss (ICC = 0.313). In contrast,
the agreement was excellent between Camarasa’s formula
and the new formula (ICC = 0.992).
The Bland–Altman diagram (Figure 1) shows that the
limits of agreement between the new formula and the other
formulas studied range from −634 to 420 mL. In the case of
the values obtained with the new formula and Camarasa’s
formula, we found a relatively high level of agreement. The
level of agreement was lower for the formulas of Gross and
of Bourke and Smith with the notable pattern that there was
higher agreement the lower the volume of blood loss; that is,
when the volume of blood loss is low, the level of agreement
between the formulas is high, but when the blood loss is high
(from approximately 1.5–2 l), the level of agreement is low.
Comparing estimates from the new formula and external
blood loss, we found a similar pattern. That is, the higher
the mean blood loss, the lower the level of agreement with
greater differences between the means.
Day 4. The Table and Figure 2 present the levels of agreement
on day 4 after surgery for the formulas studied. The ICC
shows a fair to good correlation in the case of Gross and of
Bourke and Smith formulas (0.672 and 0.491, respectively)
and an excellent correlation for our new formula (0.956).
These results can be found in Supplemental Digital Content,
Figures 1 and 2, http://links.lww.com/AA/B693, http://
links.lww.com/AA/B694.
Figure 2 shows the Bland–Altman diagrams that, in
turn, show markedly varying differences in means, ranging
from 188 mL of blood in the case of comparing the results
obtained using Camarasa’s formula and our new formula
and −1042 mL comparing Mercuriali’s formula and the new
formula.
These figures show a similar pattern to that described
previously for the data corresponding to day 2 after surgery.
We found a high level of agreement between the new for-
mula and Camarasa’s formula, whereas the agreement with
Gross’ formula fell as the mean volumes obtained with the
formulas increased.
A similar pattern is observed for the level of agreement
between the new formula and that proposed by Bourke and
Smith. In this case, when the mean volumes obtained are
low, there is a high level of agreement, but the difference
between the means obtained increases considerably for
smaller volumes.
Finally, with regard to the agreement with Mercuriali’s
formula, as we have described previously for the other
cases, we observed a clear pattern, namely, as the mean
blood loss increases, the differences between the mean val-
ues obtained using the 2 formulas (Mercuriali and new for-
mula) also increase.
DISCUSSION
In light of the results of the present study, it can be said that
the choice method (1 of various formulas based on anthropo-
metric and laboratory parameters or an objective measure-
ment of blood loss) to estimate patient blood loss did not
ANESTHESIA & ANALGESIA
 Table.   Results of the Study as a Function of the Formula Used (Day +2 and +4 After Surgery) and Evaluation of Concordance Among Them
Day +2 After Intervention New Formula
Difference in the SD of the Limits of Agreement
Estimation Method Group Estimated Blood Loss (mL) P Value ICC (95% CI) Means Difference (95% CI)
Gross’ formula Single-dose group (n = 35) 1092 ± 472 <.001 0.593 (0.454–0.704) 222 1228 −2184 (−2588; −1780)
Two-dose group (n = 35) 1150 ± 396
Placebo group (n = 36) 1669 ± 592 2628 (2224; 3032)
Total (n = 106) 1309 ± 555

July 2017 • Volume 125 • Number 1

Bourke and Smith’s formula Single-dose group (n = 35) 928 ± 408 <.001 0.472 (0.310–0.608) 420 744 −1039 (−1284; −794)
Two-dose group (n = 35) 982 ± 343
Placebo group (n = 36) 1356 ± 480 1879 (1634; 2124)
Total (n = 106) 1091 ± 454
Camarasa’s formula Single-dose group (n = 35) 1377 ± 689 <.001 0.992 (0.988–0.994) −142 120 −378 (−417; −338);
Two-dose group (n = 35) 1308 ± 641
Placebo group (n = 36) 2215 ± 1136 93 (54; 133)
Total (n = 106) 1641 ± 945
External blood loss Single-dose group (n = 35) 897 ± 335 .070 0.313 (0.123–0.481) −634 813 −2226 (−2505; −1948)
Two-dose group (n = 35) 822 ± 223 959 (680; 1237)
Placebo group (n = 36) 1003 ± 375
Total (n = 106) 909 ± 324
Day +4 After Intervention
Estimation Method
Gross’ formula Single-dose group (n = 35) 1155 ± 538 .47 0.672 (0.552–0.765) 188 1293 −2346 (−2776; −1917)
Two-dose group (n = 35) 1402 ± 975
Placebo group (n = 35) 1599 ± 647 2722 (2292; 3152)
Total (n = 105) 1388 ± 760
Bourke and Smith’s formula Single-dose group (n = 35) 984 ± 483 .032 0.491 (0.331–0.623) 456 766 −1044 (−1298; −791)
Two-dose group (n = 35) 1068 ± 571
Placebo group (n = 35) 1308 ± 526 1957 (1703; 2210)
Total (n = 105) 1120 ± 541
Camarasa’s formula Single-dose group (n = 35) 1438 ± 689 .017 0.956 (0.936–0.970) 182 300 −406 (−506; −307)
Two-dose group (n = 36) 1648 ± 1323
Placebo group (n = 36) 2142 ± 1027 771 (672; 870)
Total (n = 107) 1746 ± 1080
Mercuriali’s formula Single-dose group (n = 35) 465 ± 207 .001 0.511 (0.355–0.640) −1042 677 −2369 (−2593; −2145)
Two-dose group (n = 35) 458 ± 245
Placebo group (n = 35) 680 ± 329 286 (62; 510)
Total (n = 105) 534 ± 282
Abbreviations: CI, confidence interval; ICC, intraclass correlation coefficient; SD, standard deviation.

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 Determination of Perioperative Blood Loss
Figure 1. Bland–Altman plots for the different formulas compared with the new formula on day +2 after surgery.
affect the clinical conclusions derived from a previous study
data.23 However, using Gross’ formula, we did not observe
significant differences between the treatment groups and
placebo at 2 days after surgery. This may be because the for-
mula does not take into account transfusions that may have
been performed. Similarly, the total blood volumes of the
patients estimated using each of the methods proposed did
not differ significantly, suggesting that the choice of how
to obtain this parameter, which is required for all formulas
for calculating blood loss, does not have a marked effect on
overall differences in the result.
However, the calculated total blood loss does differ
depending on the method used, and in some cases, the dif-
ferences are sufficiently large that they could affect clinical
decisions based on a patient’s calculated blood loss with a
very low level of agreement obtained between the method
chosen as a reference for comparison (new formula) and the
others.
The current lack of an estimation method that is con-
sidered sufficiently accurate to be a gold standard has led
to the development of various different methods for esti-
mating blood loss including visual estimation, gravimetric
methods, photometry,34,35 and formulas based on laboratory
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parameters.36,37 The agreement between the estimates of
blood loss based on laboratory parameters and the objective
quantification of blood loss in the surgical field (drains and
gauzes) is also very low. The problem of underestimation of
blood loss resulting from the quantity of occult blood accu-
mulated in the patient’s soft tissue is well known,11 because
it is the difficulty in quantifying blood in gauzes and drains
in a real-life operating room setting. In this regard, several
very interesting proposals have been put forward concern-
ing validated systems for estimated the quantity of blood
accumulated in surgical gauzes involving photographing
and digitalizing the resulting photos.38
On the other hand, we must also be aware that a neces-
sary premise for using any of the hematocrit-based formulas
selected is that the patient is normovolemic, or at least that the
patient’s blood volume is similar at the start and end of the cal-
culation period. This premise is likely to be true on day 4 after
surgery, but probably invalidates the use of these formulas in
the intraoperative and immediate postoperative periods given
that volume replacement may be insufficient or excessive.39
Although goal-directed therapy based on advanced hemody-
namic parameters in a perioperative setting has been shown to
decrease morbidity/mortality in high-risk patients,40 it tends to
ANESTHESIA & ANALGESIA
 Figure 2. Bland–Altman plots for the different formulas compared with the new formula on day +4 after surgery.
indicate whether the hemodynamic status of the patient can be
optimized using fluid therapy and/or vasoactive drugs rather
than the patient’s volemic status. On the other hand, devices
for measuring bioimpedance are now available and seem to be
a promising tool for assessing intravascular volume.41
In the present study, we have considered the formula
proposed by Camarasa et al,32 which takes into account the
hematocrit values for patients at the start and end of the
calculation period as well as any volumes of homologous,
autologous, or recovered blood transfused. Second, we have
also modified this formula by replacing the estimated blood
loss for the patient calculated using the Moore method29
with that proposed by the ICSH, because this allows all
the patient’s anthropometric data (body surface area, sex)
to be included in the calculation. We believe that this may
increase the accuracy of the calculation, in particular mak-
ing it more reliable in the case of obese patients.
Third, we have included in our analysis the most widely
used formulas for estimating perioperative blood loss
found in the literature. Nevertheless, we recognize that sev-
eral others have not been included.42
Another limitation of this study is the population. None
of the formulas studied use age as a variable, and they do not
consider the differences in circulating blood volume across the
developmental stages. Moreover, they have not been tested
on morbid, cachectic, or pediatric patients. Hence, more stud-
ies are needed to test their performance in such populations.
July 2017 • Volume 125 • Number 1
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In conclusion, although there is currently no refer-
ence method for quantifying perioperative blood loss,
the use of formulas that take into account anthropometric
and laboratory parameters may be valid for research, for
instance, for evaluating the efficacy of drugs in decreas-
ing blood loss. Nonetheless, despite attempts to optimize
the formulas, the values they provide may not be suf-
ficiently accurate. Therefore, there is a need to develop
techniques that allow a more accurate quantification of
blood loss. E
DISCLOSURES
Name: A. Lopez-Picado, Pharm.
Contribution: This author helped design and conduct the study,
analyze the data, and write the manuscript.
Name: A. Albinarrate, MD.
Contribution: This author helped conduct the study, analyze the
data, and write the manuscript.
Name: Borja Barrachina, MD.
Contribution: This author helped design and conduct the study
and write the manuscript.
This manuscript was handled by: Marisa B. Marques, MD.
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