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Journal of Critical Care (2009) 24, 484491

Effect of PaCO2 variation on standard base excess value in


critically ill patients
Marcelo Park MD , Alexandre Toledo Maciel MD, Danilo Teixeira Noritomi MD,
Luciano Cesar Pontes de Azevedo MD, Leandro Utino Taniguchi MD,
Luiz Monteiro da Cruz Neto MD
Emergency Department, Intensive Care Unit, Hospital das Clnicas, University of So Paulo Medical School,
So Paulo 0563010, Brazil

Keywords:
Acidosis;
Base excess;
Outcomes;
Critical care;
Strong ion gap

Abstract
Purpose: The aim of this study was to investigate the impact of acute PaCO2 temporal variation on the
standard base excess (SBE) value in critically ill patients.
Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling
group, and 107 were allocated to the validation group. Two models were developed in the modeling
group (one including and one excluding PaCO2 as a variable determinant of SBE), and both were tested
in the validation group.
Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin,
phosphate, and PaCO2 had a predictive superiority in comparison with the model without PaCO2 (R2 =
0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F
change statistics (R2 change = 0.059, P b .001) between the model with and without PaCO2. A high
correlation (R = 0.99, P b .001) and agreement (bias = 0.25 mEq/L, limits of agreement 95% = 0.72
to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the
Van Slyke equation.
Conclusions: Acute PaCO2 temporal variation is related to SBE changes in critically ill patients.
2009 Elsevier Inc. All rights reserved.

1. Introduction
Acid-base disturbances are commonly found in critically
ill patients [1], and a consistent relationship has been
reported between these abnormalities and outcome [1-4].

Corresponding author.
E-mail address: mpark@uol.com.br (M. Park).
0883-9441/$ see front matter 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcrc.2008.12.018

There are 3 standard approaches to acid-base physiology [5]


that differ in how they access metabolic alterations (the
respiratory component is always attributed to the PaCO2
value). Among the metabolic variables, base excess (BE) is
frequently used to identify clinically significant metabolic
acidosis; and the commonly used commercially available
arterial blood gas analyzers calculate BE [5], which is the
titratable acid or base in blood necessary to restore the pH of
the sample to 7.40 while the PaCO2 is held at 40 mm Hg [6].
Because this is an in vitro analysis, some equations have

Effect of PaCO2 variation on SBE


been proposed to facilitate BE measurement; and the most
commonly used formula for calculating BE is the SiggaardAndersen Van Slyke equation [7]:
BE =1  0:023  Hbmmol=L

 HCO
3 mmol=L  24:4 + 7:7 + 2:3  Hbmmol=L
 pH  7:40g

Although calculated BE is accurate in vitro, it lacks


accuracy when applied in vivo because BE changes with
changes in PaCO2 [5,8]. This is attributed to continuous ion
exchange across the entire extracellular fluid space (blood
plus interstitial fluid). Thus, the BE equation was modified to
standardize the effect of hemoglobin and improve the
accuracy of BE in vivo. In practical terms, the hemoglobin
level used to standardize the BE equation is 5 g/dL. The term
standard base excess (SBE) has been given to this variable,
which better quantifies the change in metabolic acid-base
status in vivo [9] and also carries a correlation with clinical
outcomes in critically ill patients [4]. However, the SiggaardAndersen Van Slyke SBE equation still yields results that
seem to be slightly unstable as PaCO2 changes. This was
suggested by computer simulation [5], but it is yet to be tested
in a clinical setting. In this way, Schlichtig et al [10] treated
SBE and PaCO2 as independent variables and proposed the
equations used generally to evaluate respiratory compensation for primary metabolic disturbances and vice versa.
If acute changes in PaCO2 do have a significant impact on
SBE, there is the potential to distort bedside diagnosis and
decision making by clinicians. Therefore, the aim of this
study was to investigate the impact of acute PaCO2 temporal
variation on the SBE value in critically ill patients.

2. Methods
A total of 265 patients admitted to the intensive care unit of
a tertiary teaching hospital from February to December 2004
were enrolled in the study. Data were retrieved from a
prospectively collected database. This study was approved by
the local institutional ethics committee. Because all data were
collected in the process of routine laboratory data gathering
for all patients admitted to the intensive care unit (ICU), the
requirement for informed written consent was waived.

2.1. Laboratory techniques and measurements


All biochemical variables were collected at the time of
ICU admission and 8 to 12 hours later. All samples were
analyzed in the central laboratory of the institution. Na+, K+,
Ca2,+ and Cl were measured using the ion-selective
electrode technique; Mg2+ was measured by a colorimetric
technique based on the reaction of Mg2+ with xylidyl blue,
which forms a purple complex with decreasing levels of
absorbance. Phosphate was measured by using an ultraviolet
technique, which determines photometrically the formation

485
of a complex between inorganic phosphate and ammonium
phosphomolybdate. Albumin was measured by a bromocresol dye colorimetric technique. Arterial blood gases and
whole blood L-lactate were analyzed on the OMNI S
analyzer (Roche Diagnostics System, F Hoffmann-La
Roche Ltd, Basel, Switzerland). Standard base excess was
calculated from the measured data using the Van Slyke
equation (see below).

2.2. Acid-base mathematical calculations


According to the quantitative approach to acid-base
disturbances proposed by Stewart [11] and then modified
by Figge et al [12], and the Siggaard-Andersen SBE formula
(the Van Slyke equation modified for extracellular fluid,
hemoglobin = 5 g/dL) [7], the standard formulas used in this
study were the following:
1. SBE (Van Slyke equation) (mEq/L) = 0.9287 (HCO3
(mmol/l) 24.4 + 14.83 [pH 7.4])
2. Inorganic apparent strong ion difference (SIDai)
(mEq/L) = Na+ (mEq/L) + K+ (mEq/L) + Ca2+
(mEq/L) + Mg2+ (mEq/L) Cl (mEq/L)
3. Effective strong ion difference (SIDe) (mEq/L) = 2.46
108 PCO2/10pH + [albumin (g/dl)] (0.123 pH
0.631) + [phosphate (mg/dL)/3 (pH 0.469)]
4. SIG (mEq/L) = SIDai SIDe l-lactate (mEq/l)

2.3. Patient subgroup division and sequence


of analysis
Patients admitted during the first 7 months arbitrarily
constituted the modeling group (n = 158), and patients
admitted during the last 4 months constituted the validation
group (n = 107). Data of the modeling group were used as the
basis on which to build a mathematical multilinear model
correlating the variation (second first measurement) of
SBE between samples collected at admission and 8 to 12
hours later (dependent variable), and the variations of SIDai,
SIG, L-lactate, albumin, and phosphate (independent variables). PaCO2 variation was then introduced into the
independent variables of the model to demonstrate the
possible improvement of equation fit through the improvement of the determination coefficient (R2). To disclose any
possible nonlinear correlation of SBE and independent
variables, the standard deviation of the residuals was plotted
against the standard deviation of SBE to verify if the first
values were higher than the second, thus suggesting
nonlinearity [13].
The multilinear mathematical model was then tested in the
validation group. Standard base excess variation and the
absolute value of SBE, both predicted by the model applied
on the admission, were compared with the actual SBE
calculated using the Van Slyke equation (measured after 8-12
hours in the validation group) through correlation and

486
agreement analysis. The value attributable to each one of the
SBE partitions (SIDai, SIG, L-lactate, albumin, phosphate,
and PaCO2) was retrieved from the mathematical model while
considering all other partition variations as zero. Finally, a
subgroup of patients who had a PaCO2 variation greater than
5 mm Hg was analyzed. Some ventilatory strategies allow
acute elevations of PaCO2 as high as 30 mm Hg to avoid
alveolar hyperdistension [14]; and in cardiogenic acute
pulmonary edema patients, an increase of PaCO2 greater than
5 mm Hg has been considered an indication for tracheal
intubation [15,16]. In this way, we arbitrarily chose patients
with variation greater than 5 mm Hg to highlight the
influence of PaCO2 variation in SBE.

2.4. Statistical method details


The parametric distribution of all data was demonstrated
with the Kolmogorov-Smirnov goodness-of-fit model, and
the data were shown as means and standard deviations.
Single independent means were compared using the
Student t test. Single paired means were compared using
the paired Student t test. Categorical variables were
compared with the 2 or Fisher exact test as appropriate.
The mathematical model was built using a multilinear
regression in the enter mode. To avoid single collinearity,
Pearson correlation matrix was performed including all
independent variables (SIDai, SIG, L-lactate, albumin,
phosphate, and PaCO2), taking the R coefficient greater
than 0.85 as the single collinearity criterion [17]. Multicollinearity was considered with a tolerance value not
exceeding 0.01 and/or variance inflation factor greater than
10 [13,17]. The F change statistics were used to evaluate
the possible improvement of R2 by the introduction of a
new variable in a defined model [15]. The correlation
analysis was carried out with Pearson test, and agreement
and limits of agreement of 95% were analyzed with the
Bland-Altman plot [18,19]. The commercially available
SPSS 10.0 (Chicago, IL) statistical package was used,
taking P less than .05 as the level of significance.

3. Results
The main characteristics of patients, including laboratory
data, ICU support measures, and outcomes, are shown in
Table 1. In Table 2, analyzing the modeling group, a
mathematical multilinear regression model with SBE variation as a dependent variable is shown using SIDai, SIG, Llactate, albumin, and phosphate concentration variations as
independent variables. Afterward, Table 3 shows the
mathematical model with the inclusion of PaCO2 variation
as an independent variable, with an improvement of R2 from
0.916 to 0.978 (R2 change = 0.062, F change 248.5-318.8,
and P b .001) and without significant single or multiple
collinearity. Both equations had standard deviations of

M. Park et al.
residuals less than the standard deviation of SBE, excluding
the nonlinearity of the models.
Applying the mathematical model presented in Table 3 to
the validation group, a predictable variation of SBE and a
predictable second measure of SBE were calculated. In the
former calculation, the variations of SIDai, SIG, L-lactate,
albumin, phosphate, and PaCO2 were used as independent
variables. The values of predictable SBE second measure
and SBE variation were similar to the measured data
(Table 4). To obtain firm conclusions concerning the
influence of PaCO2 changes on SBE temporal variation, we
have performed another multilinear analysis using the
validation data set. The SBE variation was used as a
dependent variable; and 1 model included the variations of
SIG, SIDai, L-lactate, phosphate, and albumin as independent variables; the second model included the above
variables with the addition of PaCO2 variation. In the first
model, R2 was 0.936; and in the second model, R2 was 0.994
(R2 change = 0.059). The F statistics change was from
166.109 to 593.223, with P less than .001. There was no
collinearity or multicollinearity.
The similarity between measured and predicted SBE was
then complemented by the good correlation and agreement
between them (Fig. 1). Fig. 2A shows a spider plot of the
partitions related to SBE changes demonstrating that, as
occurs with SID, small variations in PaCO2 lead to significant
attributable changes in SBE. Fig. 2B shows the partitions and
SBE variations of 41 patients of the validation group with inmodule variation greater than 5 mm Hg of PaCO2.

4. Discussion
Base excess is a widely and easily used variable to
evaluate the nonrespiratory component of acid-base balance
and severity of disease in critically ill patients [1-4].
Mathematical calculations have facilitated the achievement
of a BE value [7], but inaccuracy has always been a problem
when applied in vivo because BE changes slightly with
changes in PaCO2 [5,8]. Standard base excess was developed
as a simple modification of BE to achieve independence
from PaCO2 in vivo, although a slight instability of SBE
seems to persist with PaCO2 variation (at least in computer
simulations) [5]. Metabolic acidosis disclosed by SBE or BE
reflects dysfunctions of various organs [2,4,20]. This fact can
be explained by the large number of SBE variation
determinants that can indicate renal disturbances, deficits
in the body's handling of fluids and electrolytes received
during resuscitation, perfusional variations, and cellular
dysfunction [3,4,20-24]. In line with this rationale, improvement of SBE is associated with better outcomes [4,25,26].
We would like to stress that SBE and actual BE are an
overview of metabolic acid-base status and can disclose
important metabolic acidosis depending on the clinical
setting [27]. It is a fact that there is reasonable variation

Effect of PaCO2 variation on SBE


Table 1

487

Patients' admission characteristics and laboratory data and patients' support and outcomes during ICU stay

General characteristics
Age, y
Female sex, n (%) b
APACHE II score
ICU support
Mechanical ventilation, n (%)
Renal replacement, n (%)
Vasopressors, n (%)
Inotropics, n (%)
ICU outcomes
Survivors, n (%)
Length of stay, d
Admission laboratory data
Creatinine, mg/dL
pH
SBE, mEq/L
SIDai, mEq/L
SIG, mEq/L
Lactate, mEq/L
Albumin, g/dL
PO4, mg/dL
PaCO2, mm Hg
Creatinine N2.5 mg/dL, n (%)
Syndromic admission causes
Respiratory failure
Septic shock
Severe sepsis
Cardiogenic shock
Postoperative
Neurologic
Trauma

Modeling group (n = 158)

Validation group (n = 107)

P value a

52 20
66 (42)
20 8

54 19
51 (48)
18 10

.416
.411
.073

134 (85)
17 (11)
112 (71)
95 (60)

100 (93)
11 (10)
75 (70)
66 (62)

.060
.937
.999
.900

106 (68)
10 9

77 (72)
88

.480
.065

2.0 2.0
7.31 0.12
8.0 5.7
37.4 7.0
7.9 7.2
2.9 2.6
2.4 0.6
3.2 1.9
34.7 10.7
37 (23)

2.4 2.0
7.35 0.10
6.3 5.3
38.8 6.0
8.0 6.0
2.7 1.9
2.7 0.8
4.2 1.6
34.3 9.9
27 (25)

.111
.005
.015
.092
.906
.496
b.001
b.001
0,759

51
80
12
2
4
7
2

23
52
10
1
10
9
2

.075
.842
.780
.580 c

APACHE indicates Acute Physiology and Chronic Health Evaluation.


a
P value of comparison between modeling and validation group (Student t test, 2 test, and Fisher exact test were used when appropriated).
b
n (%) denotes the number of patients and percentage over the total number of patients.
c
P value comparing cardiogenic shock, postoperative, neurologic causes of admission, and trauma as one cause of admission.

among gas analyzers when measuring SBE, depending on


the algorithm used and the clinical setting [28].
Standard base excess should be mathematically related to
PaCO2. The original question explored by this article is the
deduction of a mathematical model from a biological data
set. In this study, evaluation of the possible effect of PaCO2

variation on the SBE value was performed in vivo at the


bedsides of critically ill patients. To the best of our
knowledge, this is the first evaluation of the accuracy of
the Van Slyke SBE equation in this setting. To analyze
temporal variation, we have measured paired variables
during an 8- to 12-hour period collected from the same

Table 2 Multilinear regression in the modeling group with SBE variation as a dependent variable and variations of SBE partitions, not
including PaCO2, as independent variables (R2 = 0.916)
Partition

Unstandardized B coefficient (95% CI)

P value

Tolerance

Variance inflation factor

Constant
SIG
L-lactate
Albumin
PO4
SIDai

0.195 (0.058, 0.332)


0.967 (1.024, 0.910)
0.978 (1.056, 0.900)
2.192 (2.363, 2.021)
0.824 (0.940, 0.708)
0.977 (0.916, 1.038)

=.097
b.001
b.001
b.001
b.001
b.001

0.256
0.847
0.842
0.904
0.251

3.902
1.181
1.187
1.107
3.978

The SBE partitions were submitted to multiple correlation analysis to disclose single collinearity (all Pearson coefficients were b0.95). 95% CI denotes 95%
confidence interval of unstandardized B coefficient.

488

M. Park et al.

Table 3 Multilinear regression in the modeling with SBE variation as a dependent variable and variations of SBE partitions, including
PaCO2, as independent variables (R2 = 0.978)
Partition

Unstandardized B
coefficient (95% CI)

P value

Tolerance

Variance
inflation factor

Constant
SIG
L-lactate
Albumin
PO4
PaCO2
SIDai

0.217 (0.099, 0.335)


1.124 (1.161, 1.087)
1.183 (1.244, 1.122)
3.103 (3.503, 2.703)
0.662 (0.746, 0.578)
0.120 (0.134, 0.106)
1.126 (1.087, 1.165)

b.001
b.001
b.001
b.001
b.001
b.001
b.001

0.201
0.730
0.790
0.864
0.731
0.206

4.975
1.371
1.266
1.157
1.367
4.857

The SBE partitions were submitted to multiple correlation analysis to disclose single collinearity (all Pearson coefficients were b0.85).
95% CI denotes 95% confidence interval of unstandardized B coefficient.

patients after ICU admission. Physicochemical analysis was


used to quantify the metabolic determinants of SBE [11].
Theoretically, it is possible to conclude that the metabolic
component of the acid-base balance can be expressed by
SBE; and thus, metabolic variables of a physicochemical
nature can be correlated with SBE [2,5]. This mathematical
correlation has been recently demonstrated; and most of the
SBE variation can be explained by SIDai, SIG, L-lactate,
albumin, and phosphate variation [2]. In the present study,
the same finding was reproduced; and a high determination
coefficient (R2 = 0.916, Table 2) characterized the correlation
of the abovementioned variables with SBE variation. To
explore the importance of PaCO2 in SBE temporal variation,
it was inserted in the mathematical multilinear model (Table
3), resulting in an improvement of R2 to 0.978 without
significant single or multiple collinearity. With this analysis,
one can conclude that all observed temporal variations of
SBE in critically ill patients can be explained by the
independent variation of SIDai, SIG, L-lactate, albumin,
phosphate, and PaCO2. Hence, SBE is not an exclusive
metabolic tool because it is influenced by acute variations in
PaCO2. One can argue that PaCO2 variation can be correlated
to SBE variation due to metabolic temporal adaptation to
primary respiratory disturbances. However, if this statement
were true, PaCO2 variation would not be an independent SBE
variation predictor in the multilinear model; on the contrary,

the metabolic variable SIDai would proportionally increase


because of the chloride lost in the urine to keep the pH
constant. Such metabolic adaptation would keep SIDai as an
independent SBE variation predictor and not PaCO2.
Low values of hemoglobin can theoretically make the
actual BE (from measured hemoglobin concentration) more
accurate than the SBE to evaluate metabolic acidosis without
the interference of PaCO2 variation. We tested this hypothesis
and concluded that SBE and actual BE are both susceptible
to acute PaCO2 variation (data not shown).
Criticisms exist regarding the current equations used to
calculate SID and SIG, as proposed by Staempfli and
Constable [29]. In their work, they calculated total weak acid
concentration and its effective dissociation constant using
nonlinear regression from the measured pH and PaCO2 and
estimated SID of the plasma of 8 healthy volunteers. They
used in vitro CO2 tonometry and concluded that the SID of
Figge et al overestimates the actual value of SID. This could
also interfere in SIG calculation. To compare the SIG of
Figge et al (SIDai SIDe L-lactate) [30] and the SIG of
Staempfli and Constable ([Na+ Cl HCO3] [albumin
(g/L)][0.378/{1 + 10(7.1 pH)} 0.09]) [29], we have tested
the correlation and agreement between them (Fig. 3) as well
as the behavior of the SIG equation of Staempfli and
Constable in the mathematical model built in this study by
actually using all patients included in the data set (data not

Table 4 Standard base excess and partitions variations from admission to second measure (8-12 hours later), and mathematical model
predictable SBE and variation in validation group
Variable

Admission

Second measure

Variation (second measure admission)

SIG (mEq/L)
Lactate (mEq/L)
Albumin (g/dL)
PO4 (mg/dL)
PaCO2 (mm Hg)
SIDai (mEq/L)
Measured SBE (mEq/L)
Predictable SBE (mEq/L)

8.0 6.0
2.7 1.9
2.7 0.8
4.2 1.6
34.3 9.9
38.8 6.0
6.3 5.3

8.1
2.2
2.6
3.8
33.3
38.3
5.9
5.7

0.3 4.6
0.5 1.6
0.1 0.3
0.4 1.3
0.9 8.5
0.1 4.8
0.9 2.8
1.1 2.8

P = .763 vs predictable SBE (paired Student t test).

P = .602 vs predictable SBE variation (paired Student t test).

5.2
1.2
0.7
1.6
8.7
5.2
4.8
4.9

Effect of PaCO2 variation on SBE

489
improve the analysis of different methodologies to measure
the same phenomena, that is, the prediction of the
mathematical model and the calculation of SBE with the
Van Slyke equation, we have used correlation and agreement
between both analyzed variables [18]. The prediction from
the mathematical model correlated and agreed very well with
the Van Slyke equation (Fig. 1).
Through the mathematical model, the variation of each
of the independent variables can be individualized if the
other variables are considered to be zero. Fig. 2
demonstrates the effect of variation in PaCO2 on SBE,
which is apparently greater than that of other variables such
as weak acids. CO2 has a great distribution volume in the
body [31]; in an animal model of nonhypodynamic
pulmonary embolism, a mean time of 70 minutes is

Fig. 1 A, Correlation between measured SBE variation and


predicted SBE variation between second measure and admission. B,
Agreement between measured SBE variation and predicted SBE
variation between second measure and admission (bias = 0.25
mEq/L and limits of agreement 95% = 0.72 to 0.22 mEq/L).

shown). We concluded that the SIG equations of Staempfli


and Constable and of Figge et al are equivalent and that both
fit equally in the mathematical model.
To test the mathematical model resulting from the
modeling group analysis, the equation built was used to
predict the evolution of SBE in the validation group using the
variation of SIDai, SIG, L-lactate, albumin, phosphate, and
PaCO2 as independent variables. Some baseline acid-base
characteristics were different between the modeling and
validation groups (Table 1). However, this fact probably did
not influence the results because patient acuity or type of
acid-base disturbance should not introduce new factors that
influence SBE prediction nor should they alter the weighting
of existing independent determinants in the model [19]. The
values of SBE predicted by the mathematical model and of
SBE calculated by the Van Slyke equation in the evolution of
patients were quite similar in absolute value (Table 4). To

Fig. 2 Evolution of calculated SBE and its partitions in the


validation group. A, Spider plot revealing the dependence of SBE on
changes in the independent variables (SIDai, SIG, L-lactate, PO4,
albumin, and PaCO2). The spider plot was obtained by systematically
varying 1 independent variable while holding the other independent
variables as zero. B, Variation of SBE and SBE partitions between
the admission and second measure of patients who had variations
higher than 5 mm Hg of PaCO2.(variation N5 mm Hg = 17 patients,
16%; variation b5 mm Hg = 24 patients, 22%).

490

Fig. 3 A, Correlation between SIG calculated by the equations of


Staempfli and Constable and of Figge et al. B, Agreement and limits
of agreement between SIG calculated by the equations of Staempfli
and Constable and of Figge et al. Both analyses have used all
patients of data set.

necessary to reach a steady state of PaCO2 and end-tidal CO2


after right pulmonary artery occlusion. This long time to
steady state probably reflects the large distribution of CO2
in the body of the animal model [32]. With this rationale,
low variations of PaCO2 can be said to represent high
changes in total body CO2. Elevation in PaCO2 of 5 mm Hg
has been suggested to indicate tracheal intubation in
patients with cardiogenic pulmonary edema with or without
the support of noninvasive mechanical ventilation [15,16].
During protective ventilation in patients with acute
respiratory distress syndrome, the use of permissive
hypercapnia can reach values of 30 mm Hg greater than
the basal PaCO2 [14]. To analyze the effect of major
variation of PaCO2 on the SBE value, we chose 41 patients
(39% of the total number of patients) who had variations
greater than 5 mm Hg of PaCO2 during the study period, 17
patients who had an increased PaCO2 value, and 24 patients

M. Park et al.
who had a decreased PaCO2 value. In these patients, the
variation of SBE attributable to PaCO2 was as large as that
of SIDai (Fig. 2A, B). In fact, patients who had increases of
PaCO2 greater than 5 mm Hg had SBE variation attributable
to PaCO2 to a large degree, similar to SBE variation
attributable to SIG. Patients whose PaCO2 decreased by at
least 5 mm Hg had SBE variations attributable to SIG
with high significance, followed by variations of SBE
attributable to PaCO2 and L-lactate (Fig. 2).
The findings of this study can be explained by the fact
that a complete quantitative description of the acid-base
status of an organism requires that both intra- and
extracellular compartments should be taken into consideration [9]. In vivo evaluation of acid-base balance must
adhere to this concept, and the Van Slyke equation as well
as other BE equations fail in this approach [5]. In this way,
equations for multicompartment systems have been
described and have been shown to possess the same
mathematical interrelationships as those for single compartments [5,9]. The multicompartment form of the BE
equation is related to the traditional form of the Van
Slyke equation [9]; and with the multicompartment model,
Stewart's acid-base chemistry and BE are brought into the
same context [5]. Standard base excess quantifies the
amount of strong acid or base required to restore the SID to
baseline, at which pH is 7.40 and PaCO2 is 40 mm Hg.
Previous experiments have already demonstrated this
correlation by showing that the change in SBE is almost
equal to the change in SID across a vascular bed, even with
changes in weak acids, to keep an equilibrium at which pH
is 7.40 and PaCO2 is 40 mm Hg [22]. Mathematical
calculation of SBE based on multicompartment analysis is
theoretically less affected by PaCO2 variation.
The Van Slyke equation assumes normal values of
albumin and phosphate, which are very uncommon in
critically ill patients [5]. However, measurement of BE is
able to verify the effect of albumin and/or phosphate
variation on acid-base balance [6]. The derived equations
theoretically can detect those variations through the
instantaneous indirect effect of albumin and/or phosphate
variation on pH measurement and HCO3 calculation. In
clinical terms, the variation of SIDai, SIG, L-lactate,
albumin, and phosphate can independently explain most
of the SBE variation among critically ill patients [2].
Coefficient values found in multivariable regression
analysis of our study (Table 2) are what would be predicted
given that SBE should be a function of net charge to anions
and cations. This in agreement with Staempfli and
Constable [29] and therefore supports strong ion difference
theory and current estimates for total weak acid concentration in human plasma.
In conclusion, acute PaCO2 temporal variation is related
to SBE change in critically ill patients. In patients with
high acute variation of PaCO2, the resulting SBE change
can be of clinical importance and must be remembered by
critical care physicians.

Effect of PaCO2 variation on SBE

491

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