Zander European Journal of Medical Research (2024) 29:281 European Journal

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of Medical Research

REVIEW Open Access

Base excess (BE): reloaded

Rolf Zander1*

Summary
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, p ­ CO2 (mmHg),
­sO2 (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock,
acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed
venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.
The same applies to a therapeutic tool—then referred to as potential base excess (BEpot)—for several in vitro assess-
ments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE
or BEpot has been a parameter with exceptional clinical significance since 2007.
Keywords Base excess, Intensive care diagnostic, Mortality, Shock, Acidosis, Bleeding, Artificial ventilation, Infusion
solutions, Potential base excess, Blood products

Introduction mortality, complication rate, transfusions needs, etc. It

BE (mmol/l) is calculated routinely by each blood gas has also been shown that a potential decrease in BE from
analyzer and is defined as the amount of strong acid that hospital to ICU admission is a valid estimate of subse-
must be added theoretically to each liter of fully oxygen- quent risk. Therefore, this outstanding value Base Excess
ated blood to return the pH to 7.40 at a temperature of (BE) was named a parameter with exceptional clini-
37°C and a ­pCO2 of 40 mmHg. In everyday clinical prac- cal significance as early as 2007 and must be taken into
tice a few microlitres of each type of blood sample, i.e., account in the daily clinical routine.
arterial, mixed venous or venous, are sufficient for opti-
mal diagnostics. Any respiratory (­pCO2) or metabolic Base excess—theory
(BE) acidosis or alkalosis can be diagnosed in this way. Berend’s 2018 review article “Diagnostic use of base
The base excess (BE) or base deficit (BD, negative BE) excess in acid–base disorders” [1] started another
of arterial blood has been shown to be the best quanti- worldwide discussion about the item Base Excess (BE).
tative indicator of acute blood loss in animal models, However, since 2018, there have been several new publi-
outperforming 27 other hemodynamic parameters and cations, e.g., Langer et al. in 2022 [2]. These contain some
laboratory chemistries (Waisman et al. 1993, cited in errors as well as several incomplete sentences concerning
18). Since 1990, four clinical trials enrolling about 8,000 base excess (BE) in acid–base disorders, which is what
patients with multiple injuries have demonstrated that will be discussed in the following.
BE on admission, compared with a large number of other The physiological approach, based on the renal and lung
parameters, is indeed the best prognostic indicator for acid–base interaction [1], is patently incomplete, because
an overview with the title “The liver: The forgotten organ
in acid–base balance” was published as early as in 1995
*Correspondence: [3].
Rolf Zander The physiological facts concerning elimination of acids
[email protected]
1
Physioklin, formerly Institute of Physiology and Pathophysiology, Mainz as ­H+-ions are:
University, Mainz, Germany For lungs: 10 mmol per minute of ­CO2 (≈ ­H2CO3);
for liver: 40 mmol per hour for lactic acid alone; for

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Zander European Journal of Medical Research (2024) 29:281 Page 2 of 7

­ 2PO4− as
kidneys: 40–80 mmol per day in form of H 4. Burnett RW, Noonan DC. Calculations and cor-
+
well as ­NH4 . rection factors used in determination of blood
pH and blood gases. Clin Chem 1974; 20: 1499—
“Standard base excess is one of the most exten-
1506.
sively studied prognostic markers (…) and is pro-
5. Kofstad J: All about base excess—to BE or not
vided worldwide by most commercial blood gas
to BE (2003) Radiometer Medical ApS: G. Wen-
analyzers” [1] may be one side of the medal. It is
necke—July 24th, 2019.
inarguable that “standard BE is used widely in
clinical studies and in clinical practice throughout
the world.”
It is correct that “the nomenclature for base excess can Comment on Radiometer’s Statement:
be confusing”; the explanation for this is given by several Obviously, Radiometer “provides a number of differ-
manufacturers: ent options”, “because of clinicians may have different
In 2004, manufacturers of blood gas analyzers (Bayer preferences”. Indeed, the anesthesiologist in the ICU at
Vital, Fresenius MC, Instrumentation Laboratory, Nova night, the clinician, is interested very much in finding
Biomedical, Radiometer Germany and Roche Diag- the optimal BE value?
nostics) as well as experts in the field (e.g., Mertzlufft, The origin of Radiometer’s special policy regarding
Schaffartzik, Zander) met in Mainz (Germany) to define the calculation of Base Excess, which neglects oxygen
standard symbols and definitions related to base excess. saturation ­(sO2), can be found in a 2001 quote by J. Kof-
All the attendees except Radiometer agreed that oxygen stad: “In the clinical situation, the influence of changes
saturation ­(sO2) should be included in the calculation of in sO2 on calculation of cBase is of little importance and
Base Excess [4]. can be neglected” [5].
In 2019, however, Radiometer Copenhagen issued Also in 2019, Roche Diagnostics International Ltd
an official statement—in response to a request from issued an official statement—in response to a request
Zander—clarifying its position: by Zander—clarifying their position:
“Radiometer recognizes that clinicians may have dif- “In our current blood gas analysis systems [6], the
ferent preferences when it comes to calculation of base Zander formula for Base Excess (­BEact) is easily con-
excess and is now providing a number of different options figured. ­BEact defines base excess in blood at current
in the Instruction for Use. The algorithms are: oxygen saturation. In parallel to ­BEact, our systems also
provide guideline-recommended calculations [1] for
– cBase(B) or ABE = Actual base excess in whole blood base excess in blood (BE) and for base excess in extra-
– cBase(B, ox) = cBase(B) of fully oxygenated blood cellular fluids (­BEecf). We recommend that the system
– cBase(Ecf ) or SBE = Recognized as the in vivo software be configured according to the hospital’s
expression of base excess. It refers to a model of the needs.
extracellular fluid (one part of blood is diluted by two We are fully committed to consider new clinical guide-
parts of its own plasma) and is calculated using a lines and updated clinical practices in the development of
standard value for the hemoglobin concentration of new products. Due to regulatory constraints, we cannot
the total extracellular fluid. currently prioritize B­ Eact over BE and B
­ Eecf in our current
– Base(Ecf, ox) = cBase(Ecf ) of fully oxygenated blood.” systems. We will consider ­BEact as the prioritized formula
for base excess determination in future developments,
1. Blood Gas and pH Analysis and Related Meas- given that a careful evaluation shows the superiority of
urements; Approved Guideline—Second Edition. ­BEact in clinical practice.
CLSI document C46-A2. Wayne, PA: Clinical and
Laboratory Standards Institute 2009 [1] cobas b 123 POC system, cobas b 221 system, cobas
2. Siggaard-Andersen O. The acid–base status of the b 121 system
blood. 4th revised ed. Copenhagen: Munksgaard, [2] Clinical and Laboratory Standards Institute CLSI
1976. C46-A2 Blood gas und pH analysis and related meas-
3. Siggaard-Andersen O, Wimberley PD, Fogh- urements; Approved guideline, second edition.”
Andersen N, Gøthgen ICH: Measured and
derived quantities with modern pH and blood gas
Roche Diagnostics International Ltd
equipment: calculation algorithms with 54 equa-
R. Jäggi, R. Reynolds—September 12, 2019
tions. Scand J Clin Lab Invest 1988; 48, Suppl 189:
7–15

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Zander European Journal of Medical Research (2024) 29:281 Page 3 of 7

Comment on Roche’s statement: colleagues and medical students) are pH 7.352 ± 0.023,
Roche is waiting for a careful evaluation demonstrating ­pCO2 51.2 ± 4.9 mmHg, ­pO2 28.6 ± 10.2 mmHg,
the superiority of ­BEact in clinical practice, i.e., BE cor- ­sO2 49.2 ± 22.0%, and calculated BE as a mean was
rectly calculated including ­sO2 (%) of the blood sample. –0.1 ± 1 mmol/L. This shows that the venous and arterial
base excess difference is a methodological error only [9].
Arguments for a calculation of base excess (BE) Increasing base deficit, i.e., negative base excess, from
including oxygen saturation venous to arterial:
Authors [7] claim that, due to the lower pH and higher As an aside, the only circulation (animal study) where
­pCO2, base excess (BE) is always 1.5–2 mmol/L higher the negative base excess increases from venous to arte-
in venous blood (i.e., before lungs) than in arterial rial blood is hepatic portal circulation. pH increases by
blood (i.e., after lungs). However, the BE reflects the 0.02, ­pCO2 falls by 2 mmHg, lactate concentration is
metabolic, non-respiratory aspect of acid–base homeo- reduced by 0.44 mmol/L, and negative BE is decreased
stasis, and there should be no significant difference in by 0.43 mmol/l [10]: the metabolism of the liver con-
BE between venous and arterial blood samples, i.e., in sumes ­CO2 and eliminates H ­ + for the oxidation of lac-
the case of metabolically healthy lungs. The very unre- tate, gluconeogenesis and synthesis of urea.
alistic consequence of this would be that the lungs
would have to generate 1.5–2 mmol/L ­H+ every minute
(10,800–14,400 mmol ­H+ per day) to decrease the posi- Special statement on cotroverse O ­ 2 saturation
tive BE. This is not a controversy but a statement of right or
Rather, the reported difference in BE between venous wrong or science versus business.
and arterial blood is a method-related error resulting The story is easy to explain: One company among sev-
from use of non-optimal equations to calculate the BE. In eral others gives a statement and science contradicts it.
fact, when using the modified Van Slyke equation as per In 2001 quote by J. Kofstad, employees of Radiometer,
Zander (13—Physioklin 1/31/2012): one of the world market leaders:
  “In the clinical situation, the influence of changes in
BE = (1 − 0.0143 · cHb) · [ 0.0304 · pCO2 · 10pH −6.1 − 24.26 ­sO2 on calculation of cBase [BE] is of little importance
+ (9.5 + 1.63 · cHb) · (pH − −7.4)] − 0.2 · cHb · (1 − sO2 ) and can be neglected” [5].
In 2002 one year later, the answer from scientists
where cHb (the content of hemoglobin) is measured in [11]: Therefore, the equation according to Zander
g/100 mL and p ­ CO2 in mmHg, the last term is a correc- should be prefered to that originally proposed by Sig-
tion for oxygen saturation ­(sO2) as a fraction. This is cru- gaard-Andersen, or by the National Committee for
cial due to the fact that oxygenated Hb is a stronger acid Clinical Laboratory Standards (NCCLS), and can be
than deoxygenated Hb (the basis of the famous Chris- recommended.
tiansen-Douglas-Haldane effect, i.e., oxygenation of the for calculation of the whole blood base excess (BE) in
blood expels the ­CO2 from blood into the alveoli). the following form …
If one equilibrates a blood sample with a cHb of 15 g/ The advantage: The metabolic value BE can be obtained
dL at p­ CO2 40 mmHg and s­ O2 100% down to a s­ O2 of 0%, from any blood sample, arterial, mixed venous or venous
then the pH rises from 7.400 to 7.441, and the remaining in everyday clinical practice.
BE is constant at 0 mmol/L. The disadvantage: If the s­ O2 is not taken into account,
Therefore, the statement “Measurement of standard the BE before the lungs differs significantly from that
base excess usually requires arterial blood, which may be after the lungs, which should not be the case for a meta-
difficult to obtain in the acute care setting. Venous blood bolic value.
can be obtained more easily and more rapidly, and values The result: The BE accordding to Gattinoni et al. [7] is
for venous standard base excess generally correlate well always higher, by 1.5—2 mmol/l, in venous blood (i.e.,
with arterial values” [1] must be rejected. before the lung) than in arterial blood (i.e., after the lung),
Objection: Using the Zander Eq. (5), BE can be owing to lower pH and higher ­pCO2 values [9].
obtained with very high accuracy from any blood sam-
ple, venous or arterial, and, over a wide range of BE
(-30 to + 30 mmol/L), the mean inaccuracy is less than BE and Neonates:
1 mmol/l. The use of base excess (not standard base excess) has
The corresponding proof has been published [8]: also been studied extensively in neonates, by estimating a
typical measured results (mean ± SD) as obtained
from blood from a cubital vein (50 healthy volunteers:

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Zander European Journal of Medical Research (2024) 29:281 Page 4 of 7

hemoglobin concentration of 50 g per liter, the estimated low ­sO2 from the fetus to the mother) resulted in an
hemoglobin concentration in the extracellular fluid, one optimal proportionality of lactate vs. base excess in
third of the blood hemoglobin concentration. 278 healthy newborns. This is predicated on the cor-
SBE is valid for adults only: 5 L of blood diluted in 15 L rect calculation of the BE including the ­sO2 [13].
of extracellular space. 3. The relationship between BE and lactate values can
In neonates, however, the extracellular space makes up be appreciated from an understanding of how physi-
40% of their body weight, not 20% as in adults. Therefore, ological mechanisms within the lungs, liver, and kid-
the standard base excess must not be applied to neonates. neys interact with maintaining the acid–base balance
At a meeting in Germany in 2004 [4], the following [3]. The contribution of the liver is notable (although
experimental results were discussed: many authors regrettably overlook it, e.g., Refer-
Simulation of two neonatal blood samples (umbilical ences 2, 3) since it is responsible for the elimination
artery) by equilibration plus titration and measurement of all acids ­(H+ and lactate) and for the continuous
of acid–base status (Roche Diagnostics OMNI 9): ­pCO2 production of glucose needed for metabolic activity
55.3 and 54.0 instead of 55 mmHg predetermined by in the brain.
equilibration, ­pO2 15.8 and 16.4 instead of 15 mmHg, BE 4. Clinically, when the change in BE is less than propor-
15.2 instead of 15.0 and 21.0 instead of 20 mmol/L, when tional to that in cLac, this could be because of a ther-
the correct BE calculation formula including ­sO2 (12.4 apy with ­HCO3− or a solution for infusion containing
and 10.8%, respectively) was used. lactate [14].
In contrast, the results for use of the Radiometer for-
mula for the BE of extracellular fluid are -10.1 instead of Noteworthy is a recent study [15] which compared the
15 mmol/L, and −15.3 instead of 20 mmol/L [4]. capability of alactic base excess (aBE; representing the
influence of unmeasured anions) to a combination of BE
This shows that standard base excess (SBE) is valid
and lactate, all measured upon admission to the ICU, to
for use in only one specific clinical situation, i.e., an
predict 28-day mortality of shock patients.
adult patient with normal Hb content (g/dL), O ­2
saturation (%), and extracellular space. It cannot
be applied to neonates, because their extracellular BE and temperature
space is relatively much larger than that of adults, Unfortunately, the patient’s temperature has not been
nor to adult patients with hypoxia, anemia, or mentioned. In vitro studies have demonstrated that BE is
hypovolemia. independent of temperature [16].
In hypothermic patients, it is recommended to look
Base excess—clinical practice—diagnostic tool primarily at the ventilated patient’s BE because the
BE and lactate metabolism is diagnosed via a temperature-independent
During shock, anaerobic metabolism is reflected by BE [16].
serum lactate levels. In contrast, the BE is a calculated Thus, it is recommended that hypothermic patients
value that is influenced not only by lactic acidosis. The be ventilated according to a target value of p ­aCO2
facts: 40 ± 5 mmHg under capnometry (end-tidal) monitoring
­(petCO2, mmHg), and that the values obtained in a blood
1. The change in correctly calculated BE (Δ mmol/L gas analyzer at 37°C be corrected for the patient’s real
blood), measured in cubital venous blood, is directly body temperature using an internally validated algorithm
proportional to the lactate change (Δ lactate mmol/L (so-called pH–stat procedure).
plasma, not to the Δ lactate mmol/l blood), demon-
strated in 17 athletes during exercise load and recov-
BE and mortality
ery [12]. Naturally, the anion lactate is distributed in
BE has gained attention as a potential index to assess the
the whole extracellular space, proportionally to plasma
risk of mortality in patients with multiple injuries. This is
lactate, while the corresponding ­H+ of the lactic acid is
summarized in a review of the literature (Fig. 7, Ref. 18).
buffered mostly by hemoglobin, characterized by the
Of course, this data cannot establish that base excess—
base excess of blood.
at hospital admission—is indeed the cause of the
2. The same optimal proportionality of lactate vs. base
observed mortality.
excess was demonstrated in the neonatal clinical
Back to the chapter BE and Lactate:
situation: the measurement of lactate in the umbili-
Within the cited recent study [15] which compared the
cal vein (blood with high ­sO2 from the mother to the
capability of alactic base excess (aBE) upon admission to
fetus) as well as in the umbilical artery (blood with

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Zander European Journal of Medical Research (2024) 29:281 Page 5 of 7

BE and coagulation
In the acute setting, base excess (BE) may also be cor-
related with the risk of potentially fatal coagulation dis-
turbances in patients with trauma. Coagulopathy in
exsanguinating patients is almost always caused by acido-
sis and hypothermia; this is well documented.
A significant (p < 0.001) correlation between prothrom-
bin level (%) and negative base excess was found—in
vivo—in 4066 out of a total of 20,815 severely injured
(ISS ≥ 16) multiple-trauma patients in the Trauma Regis-
Fig. 1 [taken from18] Mortality vs. base excess (BE) in multiple try of the German Society of Trauma Surgery (Deutsche
trauma patients: Correlation between mortality (%) and base excess Gesellschaft für Unfallchirurgie) receiving primary care
(mmol/L) on hospital admission and 24 h thereafter * in a population [14].
of approximately 8200 patients selected from about 15,300 patients These bench and bedside findings therefore suggest
[80, 321,326, 347]
that a base deficit of approx. 15 mmol/L reduces clot-
ting activity to approx. 50%, which secondly explains the
reported mortality rate of approximately 50% in multiple-
trauma patients.
Further studies—in vitro—using three selected coagu-
lation factors have shown that clotting factor activity is
primarily determined by pH or BE; clotting factor activ-
ity halved at BE −12.5 mmol/L (pH 7.20) and doubled
at BE + 16.5 mmol/L (pH 7.60). This observation was
recently corroborated in patients in vivo, see above.
To summarize, the pattern of volume or blood com-
ponent therapy requires an urgent revision [17]: initially,
balanced colloids; followed by plasma (volume, coagula-
tion factors, acidosis prevention), and then fresh RBCs.
So far, this article has described use of the base excess
Fig. 2 [taken from18] Negative base excess (mmol/L during storage
of packed red cell (PRC) or whole blood (WB) units with and without
(BE) as a calculated value for diagnostic use related to,
leukocyte depletion [20] e.g., shock, metabolism, temperature, clotting. However,
there is another side, too: BE is a useful parameter for
various therapies, e.g., administration of sodium bicarbo-
the ICU to a combination of BE plus lactate, it is impor- nate or intravenous fluids, i.e., BE for therapeutic use.
tant to emphasize the following:
Base excess—therapeutic tool—potential base
1) A number of 143 shock patients are not comparable excess (BEpot)
with 8,200 multiple trauma patients in Fig. 1, because BE and solutions for infusion
shock is a special case for the formation of lactates For this purpose, the diagnostic BE has been modified to
due to a lack of oxygen, i.e., the diagnostic use of lac- obtain the therapeutic BE as follows: BE, defined in anal-
tate as a marker of hypoxia is probably unique. ogy to blood, indicates the amount of H­ CO3 required to
2) In addition to the time point of ICU admission, the bring the pH of the (acidic) solution for infusion to the
so-called lactate clearance, i.e., the decreasing lactate normal pH of 7.4. The BEpot (mmol/L) indicates the
concentration over hours after the shock event, is an amount of H ­ CO3 that can potentially be released in the
ideal method for assessing the course of the shock. body after infusion and metabolism of anions [18]. This
3) Many clinicians apparently are not aware that the use value is calculated by adding BE (with a negative sign) in
of lactate-containing infusion fluids (such as Ringer´s mmol/L to the sum of metabolizable anions, taking into
Lactate RL with 27 mmol/l lactate or older infusion account their valence.
solutions with up to 45 mmol/l lactate) or blood The concept of potential Base Excess (BEpot; mmol/L)
products (such as packed red cells (PRC) to about 50 was introduced in 2006 as an index describing the effect
mmol/l increasing during storage, as shown in Fig. 2). of an intravenous fluid on acid–base equilibrium, i.e.,

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Zander European Journal of Medical Research (2024) 29:281 Page 6 of 7

whether it has an alkalizing or acidifying effect [18]. the patient’s liver function is intact—secondary alkalosis
Unfortunately, this index has not yet been adopted by (BEpot + 30 mmol/L) (cf. Fig. 14 in Reference 18).
manufacturers, which recently prompted an urgent call The transfusion of plasma alters the situation. The bal-
for them to do so by an interdisciplinary international ance between the acidifying BE of red cells (production
group of authors [19]. process and formation of lactic acid) and the potentially
The BEpot, first recommended for solutions for infu- alkalizing effect of citrate within the plasma produces the
sion in 2006 [18], is actually accepted for labelling crystal- following result: PRC is an acidifying and plasma an alka-
loid and colloid solutions by pharmaceutical companies lizing product, as practically no alkalizing component of
in Germany. citrate remains in the PRC unit, i.e., 3 mmol/L (14).
After infusion and anion metabolism, a solution with
a BEpot of 0 mmol/L (e.g., a solution for infusion with
24 mmol/L of acetate instead of H ­ CO3) has no effect Conclusion
on the patient’s acid–base balance: neither acidosis nor The optimal requirement for clinically practicable diag-
alkalosis. nostics is: Kiss, i.e., Keep It Simple and Safe. The Base
In 2022, eleven authors from different countries dis- excess BE (mmol/L) is such a diagnostic tool in vivo. In
cussed this BEpot (mmol/l) and came to the follow- everyday clinical practice, a few microlitres of of blood,
ing conclusion [19]: “We recommend strongly that the no matter whether arterial, mixed venous or venous, are
medical community take Lönnqvist’s appeal (’time for sufficient in any blood gass analyzer for optimal diag-
a solution’) seriously and urge medical companies and nostics of each metabolic acidosis or alkalosis. The BE
manufacturers to provide improved infusion solutions or BD (base deficit) in about 8,000 patients with multiple
that are physiologically composed and balanced (Table 1), injuries have demonstrated that BE on ICU admission is
and which include clear and detailed guidance for their indeed the best prognostic indicator for mortality, com-
safe and effective use. We believe that these relatively plication rate, transfusions needs, etc. Additional, the
simple steps, which can be achieved without increasing potential base excess (BEpot, mmol/L) as an therapeutic
costs, will have a substantial clinical benefit in reducing tool in vitro for any infusion solution or blood product
morbidity and potentially saving lives.” indicates the amount of bicarbonate that can potentially
be released in the body after infusion or transfusion
related to the metabolism of anions. Therefore, this out-
BE and blood products
standing value Base Excess (BE) was named a parameter
Base excess was found to be superior for detecting hypo-
with exceptional clinical significance.
volemic shock and stratifying patients in hemorrhagic
shock with respect to the need for early transfusion of
blood. Author contributions
The transfusion of erythrocytes in the form of packed R.Z. wrote the manuscript
red cells (PRCs) is increasingly being viewed critically. A Funding
condensed summary of this view is reflected in the title Not applicable.
of a 2008 editorial: “New blood, old blood, or no blood?”
Availability of data and materials
[6]. Not applicable.
Blood products represent the classical field of applica-
tion for BEpot [18]. Packed red blood cells (PRCs) are Declarations
known to have a negative BE even at the time of prepa-
ration. Theoretically, this BE value would be approxi- Competing interests
The authors declare no competing interests.
mately 20 mmol/L, since bicarbonate normally present
in blood (20 mmol/L blood) is almost completely elimi- Ethics approval
nated during the packing process. During storage, usu- Not applicable for this—literature review—therefore, statements on consent
to participate and consent to publish are not required.
ally at 4 °C for a maximum of 42 days [2], the negative
BE of the PRCs increases to -50 mmol/L due to the pro-
duction of lactic acid by anaerobic metabolism (cf. Fig. 14 Received: 22 December 2023 Accepted: 15 March 2024
in Reference 18). Stored whole blood has a baseline BE
of approximately –15 mmol/L on account of the alka-
lizing effect of plasma citrate (20 mmol/L; with a meta-
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