Measurement of acid–base resuscitation endpoints: lactate, base
deficit, bicarbonate or what?
Michael S. Engleharta and Martin A. Schreiberb
Purpose of review
Inadequate oxygen delivery to the tissues frequently results
in significant metabolic acidosis. The resultant cellular and
organ dysfunction can increase morbidity, mortality and
hospital stay. Early diagnosis of shock can lead to early
resuscitation efforts that can prevent ongoing tissue injury.
This review focuses on the metabolic, hemodynamic and
regional perfusion endpoints utilized in the diagnosis of
metabolic acidosis resulting from shock. Resuscitation
strategies aimed at supranormal oxygen delivery will be
discussed.
Recent findings
Serum pH, lactate, base deficit and bicarbonate have all
been extensively studied as clinical markers of metabolic
acidosis in shock. While their trend helps guide
resuscitation, no single marker or specific value can be
utilized to guide resuscitation for all patients. Hemodynamic
parameters and regional tissue endpoints are designed to
identify compensated shock before it progresses to
uncompensated shock. Resuscitation strategies initiated in
the early phases of shock can reduce complications and
death. Efforts to resuscitate patients to supranormal oxygen
delivery endpoints have demonstrated mixed success, with
several notable complications.
Summary
Despite the large number of endpoints available to the
clinician, none are universally applicable and none have
independently demonstrated improved survival when
guiding resuscitation. Patients who respond well to initial
resuscitation efforts demonstrate a survival advantage over
nonresponders.
Keywords
base excess, bicarbonate, lactate, resuscitation endpoints,
supranormal oxygen delivery
Curr Opin Crit Care 12:569–574. ß 2006 Lippincott Williams & Wilkins.
a
Department of Surgery and bTrauma/Critical Care Section, Oregon Health &
Science University, Portland, Oregon, USA
Correspondence to Martin A. Schreiber, MD, FACS, Associate Professor of
Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Road,
L223A, Portland, OR 97239, USA
Tel: +1 503 494 5300; fax: +1 503 494 6519; e-mail: schreibm@ohsu.edu
Current Opinion in Critical Care 2006, 12:569–574
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Abbreviations
ICU intensive care unit
NIRS near-infrared spectroscopy
PAC pulmonary artery catheter
PCCO pulse contour wave analysis
ß 2006 Lippincott Williams & Wilkins
1070-5295
Introduction
Tissue hypoxia and the subsequent acidosis following
shock can result in cellular destruction, organ dysfunction
and death [1]. Resuscitation efforts during shock are
guided towards improvement in hemodynamic and meta-
bolic markers of global and regional tissue perfusion.
Unfortunately, no single value has proven superior in
the diagnosis of shock or in the ability to effectively guide
resuscitation efforts. This review discusses the myriad
of metabolic, invasive and noninvasive measurements of
shock. These include serum pH, lactate, base deficit and
bicarbonate, as well as devices such as the pulmonary
artery catheter (PAC), buccal and gastric capnography,
and near-infrared spectroscopy (NIRS). Various resusci-
tation strategies such as supranormal oxygen delivery
based on these endpoints will be discussed.
Shock and acidosis
Shock is best defined as inadequate tissue perfusion and
thereby an impairment of oxygen delivery. Regional
hypoxia results in anaerobic metabolism which produces
two ATP molecules (vs. 36 in aerobic metabolism) and
pyruvate which is converted into lactic acid (Fig. 1).
Prolonged and severe tissue hypoperfusion results in
the generation of large quantities of hydrogen ions
(Hþ) from lactic acid.
Markers of shock have been extensively used to both
diagnose shock and guide resuscitation efforts. Traditional
hemodynamic markers such as blood pressure, heart rate
and urine output can easily guide resuscitation efforts
during uncompensated shock when they remain abnormal
despite initial resuscitation efforts. These traditional
parameters frequently normalize, however, despite
ongoing tissue hypoxia potentially leading to delayed
organ failure and death [2]. In patients with severe sepsis,
microvascular blood flow alterations have been documen-
ted despite apparent hemodynamic stabilization [3].
This has been described as ‘compensated shock’ and
it occurs when hemodynamic parameters have been
569
 570 Trauma
Figure 1 Glycolysis
Glucose
Glycolysis
(2 ATP)
Pyruvate Lactate
Oxidative O2
phosphorylation
(36 ATP)
CO2 + H2O
Glucose is converted into pyruvate with the generation of two ATP. In the
presence of oxygen, 36 ATP are produced during oxidative phosphoryl-
ation along with carbon dioxide and water. Under anaerobic conditions,
oxidative phosphorylation cannot be performed, and pyruvate is con-
verted into lactate.
stabilized through compensatory mechanisms despite
ongoing inadequate tissue oxygenation. A primary goal
in resuscitation is to detect these changes in tissue oxygen-
ation before cardiovascular collapse. During this phase of
compensated shock, better endpoints are needed to guide
resuscitation efforts and to determine when to stop resus-
citation. The complications of over-resuscitation have
been well documented, and include abdominal compart-
ment syndrome, acute respiratory distress syndrome and
organ failure. The ideal endpoint should be readily obtain-
able, easily interpretable and have a high degree of con-
sistency across the population.
Metabolic parameters
Serum pH, base deficit, lactate and bicarbonate have all
been demonstrated to be metabolic indicators of the
severity of shock, and help determine the adequacy of
resuscitation. They have also proven to be more useful
than estimated blood loss, heart rate and blood pressure
[4]. These metabolic endpoints represent only global
tissue hypoxia, but can provide a consistent measurement
of the extent of shock.
Lactate
Initial serum lactate levels in patients in shock have been
demonstrated to correlate with outcome and have been
utilized extensively to guide resuscitation [5]. Lactate
trends over time are, however, more predictive of mortality
than initial values. In a review of trauma patients resusci-
tated to supranormal oxygen delivery values, patients
whose lactate normalized (serum levels below 2 mmol/l)
by 24 h had a 0–10% mortality; those who normalized by
24–48 h had a 25% mortality; those who normalized above
48 h after injury had an 80–86% mortality [6]. Further-
more, initial and peak lactate levels correlate with multiple
organ dysfunction syndrome following trauma [7]. In a
review of lactate and base deficit in 30 ruptured abdominal
aortic aneurysm patients, Singhal et al. [8] found that
lactate was an independent predictor of mortality with a
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
sensitivity of 87% and a specificity of 80%, and significantly
correlated with base deficit. While elevated serum lactate
levels signify global tissue hypoxia and shock, there is,
however, no clear cutoff value to guide resuscitation. Its
use as a resuscitation endpoint to improve survival has yet
to be demonstrated.
Base deficit
Base deficit (BD) is defined as the amount of base (mmol)
required to raise 1 l of whole blood to the predicted pH
based on the pCO2. The base deficit is derived from
values obtained in an arterial blood gas and calculated
using the formula [9]:
BD ¼ ½ðHCO3 Þ  24:8 þ ð16:2  ðpH  7:4ÞÞ :
Given that it is an indirect value, its clinical utility has
been as a surrogate marker of metabolic acidosis, especi-
ally lactic acidosis. Base deficit has been proven to be
superior to pH likely due to the significant compensatory
mechanisms in place to maintain a normal pH [10]. Davis
et al. [11] classified base deficit according to severity: mild
(2–5 mmol/l), moderate (6–14 mmol/l) or severe (above
15 mmol/l). The severity of the deficit directly correlated
with the volume of crystalloid and blood replaced within
the first 24 h. Failure to normalize the base deficit also
correlated directly with mortality. A base deficit of
6 mmol/l or more has been demonstrated to be a marker
of severe injury, but the predictive value varies depend-
ing on the age of the patient [12].
In an analysis of base deficit and oxygenation failure
(alveolar–arterial gradient) in burn patients, Cancio
et al. [13] demonstrated that base deficit was an inde-
pendent predictor of mortality; however, unlike the
alveolar–arterial gradient, it was unable to predict
the timing of death. Administration of sodium bicarbon-
ate can confound the utility of base deficit as an end-
point for resuscitation. Furthermore, an elevated base
deficit is thought to represent the presence of unmea-
sured anions and is usually viewed as a surrogate marker
for lactic acidosis [14]. Additional metabolic derange-
ments such as hyperchloremic acidosis from normal
saline administration, renal failure or diabetic ketoaci-
dosis can produce a metabolic acidosis that is unrelated
to tissue ischemia or ongoing shock [15]. Circulating
anions associated with the Krebs cycle have also been
shown to significantly affect interpretation of anion gap
metabolic acidoses [16]. Misinterpretation of the base
deficit may result in unnecessary interventions such as
excessive fluid resuscitation, blood transfusion and
operative intervention. Base deficit resulting from
causes other than lactic acidosis is not associated with
increased mortality [14]. While base deficit may be
useful to trend the effects of resuscitation, it cannot
be interpreted as a definitive endpoint.

Bicarbonate
Similar to base deficit, decreased levels of bicarbonate
are a reflection of metabolic acidosis. Plasma bicarbonate
acts as a buffer for serum hydrogen ions released
during anaerobic metabolism, and therefore decreases
as the acidosis worsens. In both critically ill trauma
patients and patients in the surgical intensive care unit
(ICU), bicarbonate was found to better predict acidosis
and identify nonsurvivors than pH, anion gap and lactate
[17,18]. This obviates the need for an arterial blood
gas, although these conclusions were only applicable to a
metabolic acidosis. In these studies the mean bicarbonate
values for nonsurvivors were 17.7 and 17.5 vs. 19.8 and
20 mEq/l in survivors for trauma patients and surgical
ICU patients, respectively. Despite these findings, the
serum bicarbonate level reflects only global tissue
hypoxia. It is mainly limited to evaluations of metabolic
acidosis and is subject to the same confounding metabolic
derangements as base deficit. As with the previous
metabolic markers of shock, the use of serum bicarbonate
as an endpoint of resuscitation has yet to demonstrate
improved survival.
Hemodynamic monitoring devices
The development of the pulmonary artery catheter
(PAC) has led to additional hemodynamic parameters
that can be utilized to measure intravascular volume
status, cardiac performance and diagnose shock. Volu-
metric and oximetric PACs have the additional capacity
for dynamic measurements. Continuous cardiac output
monitoring has allowed the measurement of ventricular
power and end diastolic volume index. Cheatham et al.
[19] demonstrated that cardiac index correlated better
with right ventricular end diastolic volume index
than with pulmonary artery pressure in mechanically
ventilated patients.
The use of PACs is not without disadvantages, however.
Observational studies have suggested that PACs increase
mortality, ICU length of stay, hospital costs and the
utilization of resources [20]. A recent meta-analysis of
13 randomized clinical trials evaluating PACs demon-
strated that their use did not improve survival or decrease
hospital length of stay [21]. The authors concluded that
PACs should not be routinely used in surgical ICU
patients unless effective therapies can be found that
improve outcomes when used in conjunction with the
catheter. Similarly, a randomized controlled trial on the
use of PACs vs. central venous catheters in the treatment
of acute lung injury demonstrated no improved survival
and twice the rate of catheter-associated complications
[22]. The lone study to demonstrate any benefit from
PACs concluded that in trauma, the subset of older
patients and those in severe shock have a survival benefit
when managed with a PAC [23]. This was, however, a
retrospective analysis of the National Trauma Data Bank.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Acid–base resuscitation endpoints Englehart and Schreiber 571
Figure 2 Picture of PiCCO plus instrument and waveform used
to calculate cardiac output
From Pulsion Medical Systems, Munich, Germany (http://www.pulsion.
com/index.php?id=40).
Pulse contour wave analysis (PCCO) can continuously
measure cardiac output with less-invasive techniques.
The use of the arterial waveform to calculate cardiac
output was originally described in 1899, but failed to gain
recognition until 1983 [24,25]. This method is complicated
by frequent recalibration due to rapid changes in the
hemodynamic status. Newer techniques require the pla-
cement of an arterial catheter and central venous catheter
on opposite sides of the diaphragm, thereby avoiding the
increased complication rates associated with PACs. Using
the thermodilution technique, a bolus of cold fluid is
infused into the central venous catheter and the results
are interpreted in the femoral artery catheter (Fig. 2).
PCCO may be a more accurate indicator of cardiac preload
than central venous pressure or wedge pressure. Goedje
et al. [26] demonstrated good correlation between the
traditional pulmonary artery and femoral artery thermo-
dilution techniques in cardiac surgery patients. Animal
models have also demonstrated good correlation between
PCCO and femoral artery thermodilution techniques to
calculate cardiac output [27,28]. PCCO can also be used to
determine pulse pressure variation and extravascular lung
water. No randomized clinical trials have, however, com-
pared PCCO with traditional techniques in the manage-
ment of critically ill patients.
Regional perfusion endpoints
Metabolic and hemodynamic resuscitation endpoints
reflect global alterations in homeostasis secondary to
shock. Regional perfusion endpoints are designed to
detect hypoperfusion in the microvasculature before
progressing to systemic shock. In a comparison of
multiple regional vs. global variables, regional endpoints
better predicted outcome following resuscitation [29].
Capnometry
Buccal/sublingual and gastric capnometry utilize
increases in tissue pCO2 to reflect an abnormal oxygen
delivery. They are based on the fact that the splanchnic
 572 Trauma
and oral mucosa are exquisitely sensitive to decreases in
tissue oxygen delivery which is reflected in accumulation
of pCO2 within the tissues. Ideally, tissue hypoxia and
shock would be diagnosed before their effects progress to
cardiovascular collapse. In hemorrhagic shock studies in
animals, buccal and sublingual capnography have been
shown to directly correlate with blood pressure, cardiac
output and tissue perfusion, and more accurately predict
mortality than blood pressure [30,31]. Similarly, clinical
studies in septic patients have demonstrated that sub-
lingual capnometry can effectively determine changes in
regional microcirculatory blood flow [32]. In a clinical
trial of ‘splanchnic-guided therapy’ with gastric tonome-
try compared with conventional management strategies,
no differences in mortality, organ dysfunction, or length
of stay were seen [33]. Gastric tonometry analysis is,
however, hindered by endogenous gastric acid secretion,
H2 blockers and nasogastric enteral nutrition [34,35].
Furthermore, there is significant variability in tissue
pCO2 levels within a population of normal individuals,
making standardization of this technique difficult.
Near-infrared spectroscopy
NIRS technology utilizes chromophores such as hemo-
globin to detect differences in absorption (hemoglobin
vs. deoxyhemoglobin) within the near-infrared region of
visible light (Fig. 3) [36]. It allows the measurement of
tissue oxygenation, pO2, pCO2 and pH. In animal models
of hemorrhagic shock, measurement of tissue oxygen-
ation correlated closely with measured hemodynamic
parameters and was better able to discriminate ‘respon-
der’ from ‘nonresponder’ animals compared with lactate
or global oxygen delivery [37]. McKinley et al. [38]
evaluated NIRS in severely injured trauma patients
and found that measurement of tissue oxygenation cor-
related well with oxygen delivery, base deficit and lactate
levels. NIRS is also capable of monitoring mitochondrial
Figure 3 Differences in the absorption of oxyhemoglobin (HbO2; solid lines) vs. deoxyhemoglobin (Hb; dashed lines) [36]
Specific extinction 0.08
coefficient (μM−1 cm−1)
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0.00
500 600 700 800 900
Wavelength (nm)
The graph on the right is a magnification, focusing on the absorption differences seen between 650 and 1000 nm. Near-infrared spectroscopy utilizes
differences seen between the two in this near-infrared region (700–1000 nm) to calculate tissue oxygenation.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
oxygen consumption via cytochrome aa3. Normally, tis-
sue oxyhemoglobin levels and cytochrome aa3 levels are
tightly coupled. In a clinical study of severely injured
trauma patients, Cairns et al. [39] noted that decoupling of
cytochrome aa3 was present in nine of 24 patients who
developed multiple organ failure, but only two of 16 who
did not. This technology is gaining popularity, but has
failed to demonstrate improved survival with its use.
Resuscitation techniques
Oxygen delivery (DO2) to the tissues is a function of
cardiac index (CI), hemoglobin (Hb) and oxygen satur-
ation (SaO2) as seen in the Fick equation:
DO2 ðml=min=m2 Þ ¼ CI  13:4  Hb  SaO2 :
Many have attempted to define the oxygen consumption/
delivery endpoint itself, but with no clear results. In 1988,
Shoemaker et al. [40] observed that in critically ill trauma
patients, survivors had above-normal oxygen delivery and
oxygen consumption values. Based on these results, it was
hypothesized that ‘driving’ the physiology of severely
injured patients to supranormal values would increase
survival. This has become known as ‘supranormal resus-
citation’, and it aims to maintain CI > 4.5 l/min/m2,
DO2I > 600 ml/min/m2 and VO2I > 170 ml/min/m2. Sev-
eral authors have advocated that this regimen reduces
morbidity and mortality in critically ill patients [41,42].
Recently, Pearse et al. [43] randomized high-risk surgi-
cal patients to supranormal resuscitation or conventional
management. Patients resuscitated to supranormal end-
points received more fluids and vasoactive medications.
They had fewer complications and a reduced hospital
stay, although there was no difference in mortality.
A recent meta-analysis by Poeze et al. [44] supported
these findings. Reviewing 30 randomized controlled trials
Specific extinction 0.0040
coefficient (μM−1 cm−1)
0.0020
0.0000
1000 650 700 750 800 850 900 950 1000
Wavelength (nm)

in adults, they found that supranormal oxygen delivery
resuscitation resulted in decreased mortality, but this was
not seen in patients with sepsis or organ failure. The
majority of the studies, however, focused on periopera-
tive surgical patients, which when pooled demonstrated a
survival benefit. Studies of patients with sepsis and overt
organ failure demonstrated no benefit with supranormal
resuscitation. Overall, the meta-analysis concluded that
hemodynamic optimization strategies might be
beneficial, but there were no significant differences in
outcomes between groups. As originally observed by
Shoemaker in 1988, Velmahos et al. [45] concluded in
2000 that patients who achieved supranormal oxygen
delivery goals had a better survival; however, this was
not a function of the supranormal resuscitation, but rather
the patient’s own ability to achieve these parameters
independent of forced hemodynamic optimization.
Earlier reports by Gattinoni et al. and McKinley et al. in
randomized controlled trials, and Heyland et al. in a meta-
analysis demonstrated that no such benefit of supranormal
oxygen delivery existed [46–48]. Furthermore, supranor-
mal resuscitation can be associated with significant com-
plications. Improvements in blood pressure and cardiac
performance by vasoactive drugs can be negated by
reduced tissue perfusion and can worsen ongoing tissue
ischemia. The use of dobutamine to augment oxygen
delivery in critically ill patients may actually increase
mortality, while the increased administration of intrave-
nous fluids can result in abdominal compartment syn-
drome, coagulopathy and congestive heart failure [49,50].
In summary, supranormal resuscitation may offer a sur-
vival benefit when initiated in the perioperative period,
but no survival advantage has been observed in trauma or
patients with sepsis. Furthermore, supranormal resusci-
tation utilizes significantly greater volumes of fluid and
has been associated with numerous complications.
Conclusion
Tissue hypoxia from shock results in the accumulation of
hydrogen ions with a resultant metabolic acidosis. The
treatment of shock is imperative to restore cellular func-
tion and systemic cardiovascular stability. Resuscitation
endpoints aid in the diagnosis of shock and in trending
the effectiveness of resuscitation efforts. The ability to
identify patients in compensated shock before they pro-
gress to uncompensated shock may reduce morbidity and
mortality. Currently there is no single endpoint that
universally diagnoses shock or identifies when the goals
of resuscitation have been met.
Neither bicarbonate, lactate, base deficit nor regional
perfusion endpoints have been demonstrated to be supe-
rior in the diagnosis of shock. What has proven more useful
is the trend of the resuscitation endpoints over time and
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Acid–base resuscitation endpoints Englehart and Schreiber 573
their ability to normalize within 24 h following severe
trauma. Only with frequent re-evaluation of endpoint
parameters can the resuscitation be tailored specifically
to the individual patient and change a ‘nonresponder’ into
a ‘responder’. Which endpoint is used to guide resuscita-
tion is less important than how the results are interpreted
and how the therapy is altered to return the patient to
adequate global tissue oxygenation.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 636).
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