REVIEW

CME EDUCATIONAL OBJECTIVE: Readers will note the risks associated with lactic acidosis and apply
CREDIT the recommended strategy for its treatment
ANITA J. REDDY, MD SIMON W. LAM, PharmD, FCCM SETH R. BAUER, PharmD, FCCM JORGE A. GUZMAN, MD
Quality Officer, Medical Intensive Care Unit, Department of Pharmacy, Cleveland Clinic; Medical ICU Clinical Specialist, Department of Director, Medical Intensive Care
Departments of Pulmonary Medicine and Assistant Professor, Cleveland Clinic Lerner Pharmacy, Cleveland Clinic Unit, Department of Critical Care
Critical Care Medicine, Respiratory Institute, College of Medicine of Case Western Reserve Medicine, Respiratory Institute,
Cleveland Clinic; Assistant Professor, Cleve- University, Cleveland, OH Cleveland Clinic
land Clinic Lerner College of Medicine of Case
Western Reserve University, Cleveland, OH

Lactic acidosis:
Clinical implications
and management strategies
ABSTRACT
In hospitalized patients, elevated serum lactate levels are
P hysicians are paying more attention to
serum lactate levels in hospitalized patients
than in the past, especially with the advent of
both a marker of risk and a target of therapy. The authors point-of-care testing. Elevated lactate levels are
describe the mechanisms underlying lactate elevations, associated with tissue hypoxia and hypoperfu-
note the risks associated with lactic acidosis, and outline sion but can also be found in a number of other
a strategy for its treatment. conditions. Therefore, confusion can arise as to
how to interpret elevated levels and subsequent-
KEY POINTS ly manage these patients in a variety of settings.
Serum lactate levels can become elevated by a variety of In this review, we discuss the mechanisms
underlying lactic acidosis, its prognostic im-
underlying processes, categorized as increased produc-
plications, and its use as a therapeutic target
tion in conditions of hypoperfusion and hypoxia (type A in treating patients in septic shock and other
lactic acidosis), or as increased production or decreased serious disorders.
clearance not due to hypoperfusion and hypoxia (type B).
■■ LACTATE IS A PRODUCT
The higher the lactate level and the slower the rate of OF ANAEROBIC RESPIRATION
normalization (lactate clearance), the higher the risk of Lactate, or lactic acid, is produced from pyru-
death. vate as an end product of glycolysis under an-
aerobic conditions (Figure 1). It is produced
Treatments differ depending on the underlying mecha- in most tissues in the body, but primarily in
nism of the lactate elevation. Thus, identifying the reason skeletal muscle, brain, intestine, and red blood
for hyperlactatemia and differentiating between type A cells. During times of stress, lactate is also
and B lactic acidosis are of the utmost importance. produced in the lungs, white blood cells, and
splanchnic organs.
Most lactate in the blood is cleared by the
Treatment of type A lactic acidosis aims to improve perfu- liver, where it is the substrate for gluconeogen-
sion and match oxygen consumption with oxygen deliv- esis, and a small amount is cleared by the kid-
ery by giving fluids, packed red blood cells, and vasopres- neys.1,2 The entire pathway by which lactate
sors or inotropic agents, or both. is produced and converted back to glucose is
called the Cori cycle.
Treatment of type B involves more specific management,
such as discontinuing offending medications or supple- ■■ NORMAL LEVELS
menting key cofactors for anaerobic metabolism. ARE LESS THAN ABOUT 2.0 MMOL/L
In this review, we will present lactate levels in
doi:10.3949/ccjm.82a.14098 the SI units of mmol/L (1 mmol/L = 9 mg/dL).
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 HYPERLACTATEMIA

Aerobic and anaerobic metabolism

Lactate or lactic acid accumulates under conditions of hypoxia or reduced clearance. Identifying and treating the cause is key.

Without adequate oxygen (ie, in anaerobic

metabolism), glucose provides little energy
and leaves lactate as a byproduct. However,
the lactate can be converted back to glucose
in the liver.

With adequate oxygen

(ie, in aerobic metabolism), glucose
is converted efficiently to energy,
phosphorylating ADP to ATP and leaving
only CO2 and H2O as byproducts.

FIGURE 1
Basal lactate production is approximately placed on ice, and processed quickly (ideally
0.8 mmol/kg body weight/hour. The average within 15 minutes).
normal arterial blood lactate level is approxi-
mately 0.620 mmol/L and the venous level is ■■ INCREASED PRODUCTION,
slightly higher at 0.997 mmol/L,3 but overall, DECREASED CLEARANCE, OR BOTH
arterial and venous lactate levels correlate well. An elevated lactate level can be the result of
Normal lactate levels are less than 2 increased production, decreased clearance, or
mmol/L,4 intermediate levels range from 2 both (as in liver dysfunction).
to less than 4 mmol/L, and high levels are 4 Type A lactic acidosis—due to hypo-
mmol/L or higher.5 perfusion and hypoxia—occurs when there
To minimize variations in measurement, is a mismatch between oxygen delivery and
blood samples should be drawn without a consumption, with resultant anaerobic gly-
tourniquet into tubes containing fluoride, colysis.
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 REDDY AND COLLEAGUES

The guidelines from the Surviving Sepsis TABLE 1

Campaign6 emphasize using lactate levels to
diagnose patients with sepsis-induced hypo- Causes of lactic acidosis
perfusion. However, hyperlactatemia can in-
dicate inadequate oxygen delivery due to any Type A lactic acidosis
(due to tissue hypoxia and hypoperfusion)
type of shock (Table 1).
Type B lactic acidosis—not due to hypo- Septic shock
perfusion—occurs in a variety of conditions Cardiogenic shock
(Table 1), including liver disease, malignan-
Hypovolemic shock
cy, use of certain medications (eg, metformin,
epinephrine), total parenteral nutrition, Obstructive shock
human immunodeficiency virus infection, Regional ischemia (limb, mesenteric)
thiamine deficiency, mitochondrial myopa- Seizure
thies, and congenital lactic acidosis.1–3,7 Yet
other causes include trauma, excessive exer- Shivering
cise, diabetic ketoacidosis, ethanol intoxi-
cation, dysfunction of the enzyme pyruvate Type B lactic acidosis
dehydrogenase, and increased muscle deg- (not due to hypoxia and hypoperfusion)
radation leading to increased production of Liver disease
pyruvate. In these latter scenarios, glucose
metabolism exceeds the oxidation capacity Malignancy
of the mitochondria, and the rise in pyruvate Medications (eg, metformin, epinephrine)
concentration drives lactate production.8,9 Total parenteral nutrition
Mitochondrial dysfunction and subsequent
Human immunodeficiency virus infection and treatment
deficits in cellular oxygen use can also result
in persistently high lactate levels.10 Thiamine deficiency
In some situations, patients with mildly el- Mitochondrial myopathy
evated lactic acid levels in type B lactic acido- Congenital lactic acidosis If lactate
sis can be monitored to ensure stability, rather is elevated,
than be treated aggressively. Trauma
Excessive exercise look for causes
■■ HIGHER LEVELS AND LOWER CLEARANCE Diabetic ketoacidosis of decreased
PREDICT DEATH
Ethanol intoxication oxygen delivery
The higher the lactate level and the slower
the rate of normalization (lactate clearance),
the higher the risk of death. tension and a lactate level higher than 2 mmol/L
had a significantly higher in-hospital mortality
Lactate levels and mortality rate rate than those who presented with hypotension
Shapiro et al11 showed that increases in lactate and a lactate level of 2 mmol/L or less (26% vs
level are associated with proportional increases 9%, P < .0001).14 These data suggest that elevat-
in the mortality rate. Mikkelsen et al12 showed ed lactate levels may have a significant prognostic
that intermediate levels (2.0–3.9 mmol/L) role, independent of blood pressure.
and high levels (≥ 4 mmol/L) of serum lactate
are associated with increased risk of death in- Slower clearance
dependent of organ failure and shock. Patients The prognostic implications of lactate clear-
with mildly elevated and intermediate lactate ance (reductions in lactate levels over time, as
levels and sepsis have higher rates of in-hospi- opposed to a single value in time), have also
tal and 30-day mortality, which correlate with been evaluated.
the baseline lactate level.13 Lactate clearance of at least 10% at 6 hours
In a post hoc analysis of a randomized con- after presentation has been associated with a
trolled trial, patients with septic shock who pre- lower mortality rate than nonclearance (19%
sented to the emergency department with hypo- vs 60%) in patients with sepsis or septic shock
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 HYPERLACTATEMIA

with elevated levels.15–17 Similar findings have causes of hyperlactatemia without concomi-
been reported in a general intensive care unit tant tissue hypoxia (type B acidosis).
population,18 as well as a surgical intensive Treatment differs depending on the under-
care population.19 lying mechanism of the lactate elevation; nev-
Puskarich et al20 have also shown that lac- ertheless, treatment is mostly related to opti-
tate normalization to less than 2 mmol/L during mizing oxygen delivery by giving fluids, packed
early sepsis resuscitation is the strongest predic- red blood cells, and vasopressors or inotropic
tor of survival (odds ratio [OR] 5.2), followed by agents, or both (Figure 2). The specific treat-
lactate clearance of 50% (OR 4.0) within the ment differs based on the shock state, but there
first 6 hours of presentation. Not only is lactate are similarities that can guide the clinician.
clearance associated with improved outcomes,
but a faster rate of clearance after initial presen- ■■ FLUID SUPPORT
tation is also beneficial.15,16,18
Giving fluids, with a goal of improving cardiac
Lactate clearance over a longer period (>
output, remains a cornerstone of initial thera-
6 hours) has not been studied in patients with
py for most shock states.22,23
septic shock. However, in the general intensive
care unit population, therapy guided by lactate How much fluid?
clearance for the first 8 hours after presentation Fluids should be given until the patient is no
has shown a reduction in mortality rate.18 There longer preload-dependent, although there is
are no data available on outcomes of lactate- much debate about which assessment strategy
directed therapy beyond 8 hours, but lactate should be used to determine if cardiac output
concentration and lactate clearance at 24 hours will improve with more fluid (ie, fluid-respon-
correlate with the 28-day mortality rate.21 siveness).24 In many cases, fluid resuscitation
alone may be enough to restore hemodynamic
Cryptic shock
stability, improve tissue perfusion, and reduce
Cryptic shock describes a state in a subgroup of
patients who have elevated lactate levels and elevated lactate concentrations.25
global tissue hypoxia despite being normoten- The decision to give more fluids should
Give fluids not be made lightly, though, as a more posi-
sive or even hypertensive. These patients have
until a higher mortality rate independent of blood tive fluid balance early in the course of sep-
pressure. Jansen et al18 found that patients tic shock and over 4 days has been associated
the patient is with a higher mortality rate.26 Additionally,
with a lactate level higher than 4 mmol/L and
no longer preserved blood pressure had a mortality rate pushing fluids in patients with cardiogenic
preload- of 15%, while those without shock or hyper- shock due to impaired left ventricular systolic
lactatemia had a mortality rate of 2.5%. In ad- function may lead to or worsen pulmonary
dependent, edema. Therefore, the indiscriminate use of
dition, patients with an elevated lactate level
but excessive in the absence of hypotension have mortality fluids should be avoided.
fluids may be rates similar to those in patients with high Which fluids?
lactate levels and hypotension refractory to Despite years of research, controversy persists
deleterious fluid boluses, suggesting the presence of tissue about whether crystalloids or colloids are bet-
hypoxia even in these normotensive patients.6 ter for resuscitation. Randomized trials in het-
erogeneous intensive care unit patients have
■■ HOW TO APPROACH not detected differences in 28-day mortality
AN ELEVATED LACTATE LEVEL rates between those allocated to crystalloids
An elevated lactate level should prompt an or 4% albumin27 and those allocated to crys-
evaluation for causes of decreased oxygen talloids or hydroxyethyl starch.28
delivery, due either to a systemic low-flow Hydroxyethyl starch may not be best. In
state (as a result of decreased cardiac output) a study of patients with severe sepsis, those
or severe anemia, or to regionally decreased randomized to receive hydroxyethyl starch
perfusion, (eg, limb or mesenteric ischemia). had a higher 90-day mortality rate than pa-
If tissue hypoxia is ruled out after an exhaus- tients randomized to crystalloids (51% vs
tive workup, consideration should be given to 43%, P = .03).29 A sequential prospective be-
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 REDDY AND COLLEAGUES

Lactate ≥ 4.0 mmol/L

Type A lactic acidosis (shock, regional ischemia)

Fluid-responsive? Give fluids (crystalloids or colloids)

Yes
No

Scvo2 ≥ 70%? Consider vasodilators if hemodynamically

Yes stable
No

Optimize oxygen delivery

If hypoxemic Increase arterial oxygen saturation to > 92%

If anemic Increase hemoglobin to ≥ 7.0 g/dL

(≥ 10 g/dL with cardiac ischemia)

If myocardial dysfunction Consider inotropes

If increased oxygen demand Treat underlying cause

(pain, agitation, dyssynchrony)

Type B lactic acidosis (eg, due to liver disease, medications, malignancy)

Hydroxyethyl
Treat underlying cause Recheck lactate
starch should
FIGURE 2. Management of hyperlactatemia. Scvo2 = central venous oxygen saturation. not be used
for fluid
fore-and-after study did not detect a difference goals.28–30 Until further studies are completed,
in the time to normalization (< 2.2 mmol/L) both albumin and crystalloids are reasonable resuscitation
of lactate (P = .68) or cessation of vasopressors for resuscitation. in the intensive
(P = .11) in patients with severe sepsis who Caironi et al33 performed an open-label care unit
received fluid resuscitation with crystalloids, study comparing albumin replacement (with
gelatin, or hydroxyethyl starch. More patients a goal serum albumin concentration of 3 g/
who received hydroxyethyl starch in these dL) plus a crystalloid solution vs a crystalloid
studies developed acute kidney injury than solution alone in patients with severe sepsis
those receiving crystalloids.28–30 or septic shock. They detected no difference
Taken together, these data strongly suggest between the albumin and crystalloid groups in
hydroxyethyl starch should not be used for mortality rates at 28 days (31.8% vs 32.0%, P
fluid resuscitation in the intensive care unit. = .94) or 90 days (41.1% vs 43.6%, P = .29).
Normal saline or albumin? Although However, patients in the albumin group had a
some data suggest that albumin may be pref- shorter time to cessation of vasoactive agents
erable to 0.9% sodium chloride in patients (median 3 vs 4 days, P = .007) and lower car-
with severe sepsis,31,32 these analyses should diovascular Sequential Organ Failure Assess-
be viewed as hypothesis-generating. There do ment subscores (median 1.20 vs 1.42, P = .03),
not seem to be differences between fluid types and more frequently achieved a mean arterial
in terms of subsequent serum lactate concen- pressure of at least 65 mm Hg within 6 hours
trations or achievement of lactate clearance of randomization (86.0% vs 82.5%, P = .04).
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 HYPERLACTATEMIA

Although serum lactate levels were A large, open-label trial36 detected no dif-
lower in the albumin group at baseline (1.7 ference in 28-day mortality rates in patients
mmol/L vs 1.8 mmol/L, P = .05), inspection with septic shock between those allocated to
of the data appears to show a similar daily a mean arterial pressure goal of 80 to 85 mm
lactate clearance rate between groups over Hg or 65 to 70 mm Hg (36.6% vs 34.0%, P
the first 7 study days (although these data = .57). Although lactate levels did not differ
were not analyzed by the authors). Achieve- between groups, the incidence of new-onset
ment of a lactate level lower than 2 mmol/L atrial fibrillation was higher in the higher-
on the first day of therapy was not signifi- target group (6.7% vs 2.8%, P = .02). Fewer
cantly different between groups (73.4% vs patients with chronic hypertension needed
72.5%, P = .11).33 renal replacement therapy in the higher pres-
In a post hoc subgroup analysis, patients sure group, further emphasizing the need to
with septic shock at baseline randomized to al- individualize the mean arterial pressure goal
bumin had a lower 90-day mortality rate than for patients in shock.36
patients randomized to crystalloid solutions Which vasopressor agent?
(RR 0.87, 95% CI 0.77–0.99). There was no Dopamine and norepinephrine have tradi-
difference in the 90-day mortality rate in pa- tionally been the preferred initial vasopressors
tients without septic shock (RR 1.13, 95% CI for patients with shock. Until recently there
0.92–1.39, P = .03 for heterogeneity).33 were few data to guide selection between the
These data suggest that albumin replace- two, but this is changing.
ment may not improve outcomes in patients In a 2010 study of 1,679 patients with
with severe sepsis, but may have advantages in shock requiring vasopressors, there was no dif-
terms of hemodynamic variables (and poten- ference in the 28-day mortality rate between
tially mortality) in patients with septic shock. patients randomized to dopamine or norepi-
The role of albumin replacement in patients nephrine (53% vs 49%, P = .10).37 Patients
with septic shock warrants further study. allocated to dopamine, though, had a higher
incidence of arrhythmias (24% vs 12%, P <
Norepinephrine, ■■ VASOPRESSORS .001) and more frequently required open-label
not dopamine, Vasopressors, inotropes, or both should be giv- norepinephrine (26% vs 20%, P < .001). Al-
en to patients who have signs of hypoperfu- though lactate levels and the time to achieve-
should be ment of a mean arterial pressure of 65 mm Hg
sion (including elevated lactate levels) despite
the initial preload optimization or ongoing fluid admin- were similar between groups, patients allocat-
istration. The most appropriate drug depends ed to norepinephrine had more vasopressor-
vasopressor free days through day 28.
on the goal: vasopressors are used to increase
in most types systemic vascular resistance, while inotropes An a priori-planned subgroup analysis
of shock are used to improve cardiac output and oxy- evaluated the influence of the type of shock
gen delivery. on patient outcome. Patients with cardiogenic
shock randomized to dopamine had a higher
Blood pressure target mortality rate than those randomized to nor-
The Surviving Sepsis Campaign guidelines epinephrine (P = .03). However, the overall
recommend a mean arterial blood pressure effect of treatment did not differ among the
target of at least 65 mm Hg during initial shock subgroups (interaction P = .87), sug-
resuscitation and when vasopressors are ap- gesting that the reported differences in mor-
plied for patients with septic shock.22 This tality according to subgroup may be spurious.
recommendation is based on small studies In a 2012 meta-analysis of patients with
that did not show differences in serum lac- septic shock, dopamine use was associated
tate levels or regional blood flow when the with a higher mortality rate than norepineph-
mean arterial pressure was elevated above 65 rine use.38
mm Hg with norepinephrine.34,35 However, In light of these data, norepinephrine
the campaign guidelines note that the mean should be preferred over dopamine as the ini-
arterial pressure goal must be individualized tial vasopressor in most types of shock.
in order to achieve optimal perfusion. Epinephrine does not offer an outcome
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 REDDY AND COLLEAGUES

advantage over norepinephrine and may be determinant of oxygen delivery. Cardiac out-
associated with a higher incidence of adverse put may be augmented by ensuring adequate
events.39–42 Indeed, in a study of patients with preload (by fluid resuscitation) or by giving
septic shock, lactate concentrations on the inotropes or vasodilators.
first day after randomization were significantly The optimal cardiac output is difficult to
higher in patients allocated to epinephrine define, and the exact marker for determining
than in patients allocated to norepinephrine when cardiac output should be augmented is
plus dobutamine.39 Similar effects on lactate unclear. A strategy of increasing cardiac out-
concentrations with epinephrine were seen in put to predefined “supranormal” levels was
patients with various types of shock40 and in not associated with a lower mortality rate.49
those with cardiogenic shock.42 Therefore, the decision to augment cardiac
These differences in lactate concentra- output must be individualized and will likely
tions may be directly attributable to epineph- vary in the same patient over time.23
rine. Epinephrine can increase lactate con- A reasonable approach to determining
centrations through glycolysis and pyruvate when augmentation of cardiac output is nec-
dehydrogenase activation by stimulation of essary was proposed in a study by Rivers et al.50
sodium-potassium ATPase activity via beta-2 In that study, in patients randomized to early
adrenergic receptors in skeletal muscles,43 as goal-directed therapy, inotropes were recom-
well as decrease splanchnic perfusion.42,44,45 mended when the central venous oxygenation
These effects may preclude using lactate clear- saturation (Scvo2) was below 70% despite
ance as a resuscitation goal in patients receiv- adequate fluid resuscitation (central venous
ing epinephrine. Epinephrine is likely best pressure ≥ 8 mm Hg) and hematocrits were
reserved for patients with refractory shock,22 higher than 30%.
particularly those in whom cardiac output is When an inotrope is indicated to improve
known to be low. cardiac output, dobutamine is usually the pre-
Phenylephrine, essentially a pure vaso- ferred agent. Dobutamine has a shorter half-
constrictor, should be avoided in low cardiac life (allowing for easier titration) and causes
output states and is best reserved for patients less hypotension (assuming preload has been Serum lactate
who develop a tachyarrhythmia on norepi- optimized) than phosphodiesterase type III in- > 4.0 mmol/L
nephrine.22 hibitors such as milrinone.
Mechanical support devices, such as intra- has been used
Vasopressin, also a pure vasoconstrictor
that should be avoided in low cardiac output aortic balloon counterpulsation, and vasodila- as the trigger
states, has been best studied in patients with tors can also be used to improve tissue perfu- to initiate
vasodilatory shock. Although controversy ex- sion in selected patients with low cardiac out-
ists on the mortality benefits of vasopressin in put syndromes. aggressive
vasodilatory shock, it is a relatively safe drug resuscitation
with consistent norepinephrine-sparing ef- ■■ USING LACTATE LEVELS
TO GUIDE THERAPY in patients
fects when added to existing norepinephrine
therapy.46,47 In patients with less severe septic with sepsis
Lactate levels above 4.0 mmol/L
shock, including those with low lactate con- Lactate may be a useful marker for determining
centrations, adding vasopressin to norepi- whether organ dysfunction is present and, hence,
nephrine instead of continuing norepineph- what course of therapy should be given, especially
rine alone may confer a mortality advantage.48 in sepsis. A serum lactate level higher than 4.0
mmol/L has been used as the trigger to start ag-
■■ OTHER MEASURES gressive resuscitation in patients with sepsis.50,51
TO OPTIMIZE OXYGEN DELIVERY Traditionally, as delineated by Rivers et al50
In circulatory shock from any cause, tissue oxy- in their landmark study of early goal-directed
gen demand exceeds oxygen delivery. Once therapy, this entailed placing an arterial line
arterial oxygenation and hemoglobin levels and a central line for hemodynamic monitor-
(by packed red blood cell transfusion) have ing, with specific interventions directed at
been optimized, cardiac output is the critical increasing the central venous pressure, mean
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 HYPERLACTATEMIA

arterial pressure, and central venous oxygen with fluids and vasopressors restores adequate
saturation.50 However, a recent study in a oxygen delivery for the majority of patients,
similar population of patients with sepsis with is likely as good a target for resuscitation as
elevated lactate found no significant advan- central venous oxygen saturation.
tage of protocol-based resuscitation over care This study, however, does not address the
provided according to physician judgment, question of whether lactate clearance is useful
and no significant benefit in central venous as an additional marker of oxygen delivery (in
catheterization and hemodynamic monitoring conjunction with central venous oxygen satu-
in all patients.51 ration). Indeed, caution should be taken to
target central venous oxygen saturation goals
Lactate clearance: 10% or above at 8 hours? alone, as patients with septic shock present-
Regardless of the approach chosen, decreasing ing with venous hyperoxia (central venous
lactate levels can be interpreted as an ade- oxygen saturation > 89%) have been shown
quate response to the interventions provided. to have a higher mortality rate than patients
As a matter of fact, several groups of investiga- with normoxia (central venous oxygen satura-
tors have also demonstrated the merits of lac- tion 71%–89%).54
tate clearance alone as a prognostic indicator This was further demonstrated by Arnold
in patients requiring hemodynamic support. et al in a study of patients presenting to the
McNelis et al52 retrospectively evaluated emergency department with severe sepsis.15
95 postsurgical patients who required hemo- In this study, significant discordance between
dynamic monitoring.52,53 The authors found central venous oxygen saturation and lactate
that the slower the lactate clearance, the clearance was seen, where 79% of patients
higher the mortality rate. with less than 10% lactate clearance had con-
Given the prognostic implications of lac- comitant central venous oxygen saturation of
tate clearance, investigators have evaluated 70% or greater.
whether lactate clearance could be used as Jansen et al18 evaluated the role of target-
a surrogate resuscitation goal for optimizing ing lactate clearance in conjunction with cen-
It seems oxygen delivery. Using lactate clearance may tral venous oxygen saturation monitoring. In
have significant practical advantages over us- this study, critically ill patients with elevated
reasonable ing central venous oxygen saturation, since it lactate and inadequate lactate clearance were
to measure does not require a central venous catheter or randomized to usual care or to resuscitation
lactate every continuous oximetric monitoring. to adequate lactate clearance (20% or more).
In a study comparing these two resuscita- The therapies to optimize oxygen delivery were
2 hours for the tion end points, patients were randomized to given according to the central venous oxygen
first 8 hours of a goal of either central venous oxygen satu- saturation. Overall, after adjustment for pre-
resuscitation in ration of 70% or more or lactate clearance
of 10% or more within the first 6 hours after
defined risk factors, the in-hospital mortality
rate was lower in the lactate clearance group.
patients with presentation as a marker of oxygen delivery.53 This may signify that patients with sepsis and
type A lactic Mortality rates were similar with either strat- central venous oxygen saturation of 70% or
egy. Of note, only 10% of the patients actually more may continue to have poor lactate clear-
acidosis required therapies to improve their oxygen de- ance, warranting further treatment.
livery. Furthermore, there were no differences Taken together, serum lactate may be
in the treatments given (including fluids, va- helpful for prognostication, determination of
sopressors, inotropes, packed red blood cells) course of therapy, and quantification for tissue
throughout the treatment period. hypoperfusion for targeted therapies. Figure 2
These findings provide several insights. presents our approach to an elevated lactate
First, few patients admitted to the emergen- level. As performed in the study by Jansen
cy department with severe sepsis and treated et al,18 it seems reasonable to measure lac-
with an initial quantitative resuscitation pro- tate levels every 2 hours for the first 8 hours
tocol require additional therapy for augment- of resuscitation in patients with type A lactic
ing oxygen delivery. Second, lactate clear- acidosis. These levels should be interpreted in
ance, in a setting where initial resuscitation the context of lactate clearance (at least 10%,
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 REDDY AND COLLEAGUES

but preferably 20%) and normalization, and bicarb, and tromethamine have all been stud-
should be treated with an approach similar to ied in the management of type B lactic acido-
the one outlined in Figure 2. sis, with little success.55,56
Renal replacement therapy has had some
■■ TREATING TYPE B LACTIC ACIDOSIS success in drug-induced lactic acidosis.57,58
(NORMAL PERFUSION AND OXYGENATION) l-carnitine has had promising results in
treating patients with human immunodefi-
Treating type B lactic acidosis is quite different ciency virus infection, since these patients are
because the goal is not to correct mismatches carnitine-deficient and carnitine plays an im-
in oxygen consumption and delivery. Since portant role in mitochondrial function.59
most cases are due to underlying conditions Thiamine and biotin deficiencies can oc-
such as malignancy or medications, treatment cur in patients receiving total parenteral nu-
should be centered around eliminating the trition without vitamins and in patients who
cause (eg, treat the malignancy, discontinue drink alcohol heavily and can cause lactic aci-
the offending medication). The main reason dosis. These nutrients should be supplement-
for treatment is to alleviate the harmful effects ed accordingly.
of acidosis. For example, acidosis can result in Treatment of mitochondrial disorders in-
a negative inotropic effect. cludes antioxidants (coenzyme Q10, vitamin C,
Sodium bicarbonate, dichloroacetate, car- vitamin E) and amino acids (l-arginine).60 ■
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