Intensive Care Med (2007) 33:970977

DOI 10.1007/s00134-007-0563-9

Stephen Trzeciak
R. Phillip Dellinger
Michael E. Chansky
Ryan C. Arnold
Christa Schorr
Barry Milcarek
Steven M. Hollenberg
Joseph E. Parrillo

Received: 28 July 2006

Accepted: 26 January 2007
Published online: 13 March 2007
Springer-Verlag 2007
Electronic supplementary material
The online version of this article
(doi:10.1007/s00134-007-0563-9) contains
supplementary material, which is available
to authorized users.

S. Trzeciak (u) R. P. Dellinger

M. E. Chansky R. C. Arnold C. Schorr
B. Milcarek S. M. Hollenberg
J. E. Parrillo
UMDNJ-Robert Wood Johnson Medical
School at Camden, Cooper University
Hospital, Division of Cardiovascular
Disease and Critical Care Medicine and the
Department of Emergency Medicine,
One Cooper Plaza, Camden 08103, NJ,
USA
e-mail: trzeciak-stephen@cooperhealth.edu
Tel.: +1-856-3423342
Fax: +1-856-9688306

ORIGINAL

Serum lactate as a predictor of mortality

in patients with infection

Abstract Objective: To determine

the utility of an initial serum lactate
measurement for identifying high risk
of death in patients with infection.
Design and setting: Post-hoc analysis
of a prospectively compiled registry in
an urban academic hospital. Participants: Patients with (a) a primary or
secondary diagnosis of infection and
(b) lactate measurement who were
admitted over the 18 months following hospital-wide implementation
of the Surviving Sepsis Campaign
guideline for lactate measurement in
patients with infection and possible
severe sepsis. There were 1,177
unique patients, with an in-hospital
mortality of 19%. Measurements
and results: Outcome measures
included acute-phase ( 3 days)
death and in-hospital death. We
defined lactate ranges a priori (low,
0.02.0; intermediate, 2.13.9; high,
4.0 mmol/l or above)and tested for
linear associations with mortality by
one-way analysis of variance. We
determined sensitivity/specificity,
odds ratios, and likelihood ratios for
a lactate 4.0 mmol/l and performed

Introduction
Elevation in serum lactate has been associated with an
increased risk of death in emergency department (ED)
patients with infection [1] and in heterogeneous populations of patients with sepsis [26]. Current guidelines
from the Surviving Sepsis Campaign (SSC) [7, 8] advocate lactate measurement in patients with infection and

a Bayesian analysis to determine its

impact on a full range (0.010.99)
of hypothetical pretest probability
estimates for death. In-hospital mortality was 15%, 25%, and 38% in
low, intermediate, and high lactate
groups, respectively. Acute-phase
deaths and in-hospital deaths increased linearly with lactate. An
initial lactate 4.0 mmol/l was associated with sixfold higher odds
of acute-phase death; however,
a lactate level less than 4 mmol/l
had little impact on probability
of death. Conclusions: When
broadly implemented in routine
practice, measurement of lactate in
patients with infection and possible sepsis can affect assessment of
mortality risk. Specifically, an initial
lactate 4.0 mmol/l substantially
increases the probability of acutephase death.
Keywords Lactic acid Bayesian
prediction In-hospital mortality
Infection Sepsis Severe sepsis
Septic shock

possible severe sepsis to help identify patients at high

risk of death who should be treated aggressively [9].
Based on this guideline the SSC and Institute for
Healthcare Improvement have incorporated lactate measurement into quality indicators (termed bundles) [10]
for performance improvement in sepsis resuscitation
(available at: http://www.ihi.org/IHI/Topics/CriticalCare/
Sepsis/).

971

The SSC guideline for measuring lactate is intended to

apply to patients with clinically suspected sepsis across
all hospital-based practice settings (including ED, ICU,
and non-ICU ward); however, it is currently unknown
whether lactate measurement would be useful for identifying high risk of death when this SSC guideline is
broadly implemented in routine practice in a hospital-wide
fashion. Therefore the purpose of this study was to
determine the utility of initial serum lactate measurement
to identify high risk of death in patients with infection
after hospital-wide implementation of the SSC guideline
for lactate measurement in patients with infection and
possible severe sepsis. We also performed a Bayesian
analysis of the data, as this approach can increase the
accuracy of mortality prediction for individual patients by
taking into account a clinicians subjective assessment of
mortality risk [11, 12] and therefore likely represents the
most clinically meaningful method of demonstrating the
utility of lactate measurement for mortality prediction in
clinical practice.

diagnosis of infection and serum lactate measured between

March 2004 and August 2005 (Table 1). The presence of
an infectious diagnosis was determined by post-hoc classification of final discharge diagnostic codes (an adaptation
of the methods described by Angus et al. [16] and Shapiro
et al. [1]). Two observers classified each diagnostic code as
either infectious or noninfectious based on whether the diagnosis was likely to have a bacterial or fungal cause. The
classification of diagnoses was blinded to all other patient
data. We calculated interobserver agreement for this classification of diagnoses based on a 10% sample of the registry
selected at random; the -statistic for interobserver agreement for classification of diagnoses (infectious cause) was
0.9. All subjects with either a primary or secondary diagnosis of infection were included in the final analysis. We
excluded all repeat hospitalizations within the study period so that each subject represents a unique patient. Of the
1,177 patients in the sample 952 (81%) survived to hospital discharge and 225 (19%) died. Of the 225 deaths 63
(28%) were within 3 days and 162 (72%) after 3 days.

Materials and methods

Interventions

Subjects and setting

In the 3 months (JanuaryMarch 2004) immediately preceding the study period we conducted a multidisciplinary
hospital-wide education program [13] that was based on
the recently released SSC guidelines [14]. We instructed
clinicians to measure lactate in patients with infection
and suspected sepsis to help identify high risk of death,
and we tested clinicians on this concept [13]. Next we
implemented a hospital-wide clinical practice algorithm
for sepsis resuscitation (adopted from Rivers et al. [9])
in which an initial step of the algorithm was to measure
lactate in patients with infection and suspected sepsis
in accordance with the SSC guidelines. Details of the
ED-specific elements of this implementation process are
published elsewhere [15].

This post-hoc analysis of a prospectively compiled registry was carried out in an urban academic medical center
(Cooper University Hospital, Camden, NJ, USA). It was
approved by the institutional review board, which waived
the need for informed consent. The subjects were 1,177
patients aged at least 18 years with primary or secondary

Table 1 Patient characteristics (n = 1,177)

Gender
Male
Female
Age (years)
49
5065
6675
75
Locationa
ED
ICU
Non-ICU ward
Primary source of infection
Lung
Urinary tract
Intra-abdominal
Bloodstream
Skin/soft tissue
Other
a At

the time of lactate measurement

591
586

50
50

271
331
231
344

23
28
20
29

707
261
209

60
22
18

403
285
222
83
81
103

34
24
19
7
7
9

Data source
We utilized a prospectively compiled lactate registry for
this study. Our performance improvement committee for
critical care commissioned the creation of the lactate registry in March 2004 as a tool to aid in the tracking of patients for assessment of clinician adherence to applicable
SSC guidelines. The registry was created by a two-step
automated process: (a) whenever lactate was measured in
our central laboratory, a lactate report was automatically
generated and electronically transmitted to a data manager
who entered the new case into a dedicated database; and
(b) the registry database was linked to our institutions central administrative database allowing automated importing
of data fields for demographics, diagnoses, and outcomes.

972

Measurements

Secondary analyses

Primary outcome measures included (a) in-hospital

death and (b) acute-phase death (defined a priori as 3
days from initial lactate measurement [1]). All lactate
measurements were venous and measured in a central
laboratory with an enzymatic calorimetric technique using
a lactate oxidase catalyzed reaction (Cobas Integra 800,
Roche Diagnostics). We did not analyze repeat lactate
measurements after the initial value for the hospitalization. Other data points included: demographics, infectious
diagnosis, date/time of lactate obtained, location when
lactate obtained, and (if applicable) number of days from
lactate measurement until death.

We performed two secondary analyses. First, to determine

the promptness of lactate measurement for infected patients with suspected sepsis we examined a representative
(6-month) sample of infected patients admitted during the
18-month study period who also met criteria for severe
sepsis (per SSC criteria for acute sepsis-induced organ dysfunction [17]) and performed a post-hoc analysis of the
elapsed time from meeting severe sepsis criteria to the time
of lactate measurement. Second, we performed a subgroup
analysis stratifying subjects by location where lactate was
obtained (ED vs. ICU vs. non-ICU ward).

Data analysis
We stratified the lactate values into three a priori defined groups (low, 0.02.0; intermediate, 2.13.9; high,
4.0 mmol/l or above) consistent with the cutoff values
previously utilized by other authors [2, 5]. We tested
for linear associations with mortality risk by one-way
analysis of variance with Bonferronis correction for
multiple comparisons between groups. The proportionality of differences in survival was tested by the log
rank statistic using the KaplanMeier method accounting
for censoring. Using a lactate value of 4.0 mmol/l or
higher as a cutoff for a positive test, we determined the
sensitivity/specificity, receiver operating characteristic,
odds ratios, and likelihood ratios for death.

Results
Figure 1 displays the distribution of patients by initial
lactate value and the mortality in each lactate group.
Results of the one-way analysis of variance are presented
in the Electronic Supplementary Material (S. T1, S. T2).
The number of deaths within 3 days and in-hospital deaths
increased significantly and linearly with increasing range
of initial lactate values. The overall statistical significance
of linear differences between lactate groups (log-rank
statistic) was p < 0.0001 with one degree of freedom.

Bayesian analysis
Bayesian statistics combine pretest probability estimates
with new data (in this case a lactate value 4 mmol/l)
to yield new updated posttest probabilities. First, we
generated a full range (0.010.99) sample of hypothetical
clinician pretest probability estimates for death on the
grounds that this would permit demonstration of the
impact of a lactate level higher than 4 mmol/l on the
full range of possible pretest probability estimates that
a clinician could derive from all other clinical parameters
that are available. Second, we converted these pretest
probabilities into pretest odds and multiplied them by
the likelihood ratios for death from our data. Third, we
converted these posttest odds back to probabilities to
yield the full range of posttest probabilities. Lastly, we
graphically represented the relationships between pre- and
posttest probabilities through the full range of possible
experience.

Fig. 1 Acute-phase deaths and in-hospital deaths in infected patients

stratified by initial lactate value. The number of acute-phase deaths
and in-hospital deaths increased significantly and linearly with increasing lactate

973

Figure 2 displays the KaplanMeier survival curves in the

three lactate groups, with time zero representing the day
that the initial lactate value was obtained. Table 2 presents
the findings of sensitivity/specificity, area under the curve,
odds ratios, and likelihood ratios for acute-phase and
in-hospital deaths, using a lactate cutoff of values at or
higher than 4.0 mmol/l as indicating a positive result.
Bayesian analysis
Based on the likelihood ratios for death using a lactate
cutoff at 4.0 mmol/l or higher for a positive result, Fig. 3

Fig. 2 KaplanMeier survival curves. KaplanMeier survival curves

(truncated at 28 days) for the three a priori defined groups of initial lactate values: low, 0.02.0 mmol/l (n = 827); intermediate, 2.1
3.9 mmol/l (n = 238); and high, 4.0 mmol/l or above (n = 112). Time
zero represents the day of lactate measurement. LA = lactic acid
Fig. 3 Bayesian analysis. This figure displays how the initial lactate
measurement can impact the full range (0.010.99) of possible values
for pretest probability of death determined by a clinicians bedside
Table 2 Use of an initial lactate value of 4.0 mmol/l or higher to
assessment (derived from conventional clinical parameters that are
predict mortality (CI confidence interval)
available prior to measuring lactate). Using a cutoff value for lactate at
4 mmol/l, with higher values indicating a positive result and lower valAcute-phase ( 3 days) deatha
ues a negative result, the curves are derived from the likelihood ratios
Sensitivity (%)
35 (2546)
(LR) for death observed in this study. a Impact of lactate measurement
Specificity (%)
92 (9193)
on pretest probability for death within 3 days; solid line positive LR
Area under the curveb
0.63 (0.570.69)
(4.32, 95% CI 2.886.20); dotted line negative LR (0.71, 95% CI 0.58
Odds ratio
6.1 (3.710.5)
0.82). An initial lactate level greater than or equal to 4 mmol/l can have
Relative risk
5.1 (3.28.2)
a substantial impact on pretest probability for acute-phase death. For
Likelihood ratio positive
4.3 (2.96.2)
example, if (prior to measuring lactate) a clinicians pretest probability
Likelihood ratio negative
0.71 (0.580.82)
for death within 3 days is 5%, a lactate value greater than 4 mmol/l
In-hospital death
would give a posttest probability for death within 3 days of 19%.
Sensitivity (%)
19 (1523)
Similarly, for a pretest probability of 20% a lactate value greater
Specificity (%)
93 (9194)
than 4 mmol/l would raise the posttest probability to over 50%. b
b
Area under the curve
0.56 (5359)
Impact of lactate measurement on pretest probability for in-hospital
Odds ratio
3.0 (2.04.6)
mortality; solid line positive LR+ (2.64, 95% CI 1.853.73); dotted
Relative risk
2.3 (1.72.9)
line negative LR (0.87, 95% CI 0.820.92). An initial lactate level
Likelihood ratio positive
2.6 (1.93.7)
less than 4 mmol/l has limited capacity to impact pretest probability
Likelihood ratio negative
0.87 (0.820.92)
for in-hospital death. For example, if (prior to measuring lactate) a
clinicians pretest probability for in-hospital death was 20%, a lactate
a 3 days from the time of lactate measurement
value less than 4 mmol/l would only minimally reduce the posttest
b Receiver operating characteristic
probability for in-hospital death (18%)

974

Table 3 Use of an initial lactate value of 4.0 mmol/l or higher to predict mortality: subgroup analysis stratified by hospital location (brackets
95% confidence interval, ED emergency department, ICU intensive care unit)

Patients alive
Patients dead
Dead 3 days
Dead > 3 days
Lactate values
4.0 mmol/l
< 4.0 mmol/l
Acute-phase death ( 3 days)
Sensitivity (%)
Specificity (%)
Odds ratio
Likelihood ratio positive
Likelihood ratio negative
In-hospital death
Sensitivity (%)
Specificity (%)
Odds ratio
Likelihood ratio positive
Likelihood ratio negative

ED
(n = 707, 60%)

ICU
(n = 261, 22%)

Non-ICU ward
(n = 209, 18%)

621 (88%)
86 (12%)
21 (24%)
65 (76%)

151 (58%)
110 (42%)
33 (30%)
77 (70%)

180 (86%)
29 (14%)
9 (31%)
20 (69%)

70 (10%)
637 (90%)

38 (15%)
223 (85%)

4 (2%)
205 (98%)

24 [1144]
91 [9091]
3.0 [1.18.3]
2.6 [1.15.1]
0.84 [0.610.99]

46 [3259]
90 [8892]
7.4 [3.316.5]
4.5 [2.67.3]
0.61 [0.440.78]

22 [737]
99 [9899]
28.3 [4.3188.0]
22.2 [4.1118.0]
0.79 [0.630.95]

22 [1530]
92 [9193]
3.2 [1.85.8]
2.8 [1.74.3]
0.85 [0.750.93]

20 [1525]
89 [8693]
2.1 [1.14.2]
1.9 [1.13.4]
0.90 [0.810.99]

6 [212]
99 [9899]
6.6 [1.139.1]
6.2 [1.134.6]
0.94 [0.890.99]

graphically represents how lactate measurement can affect any possible value for pretest probability for acutephase death and in-hospital death as determined by a clinicians bedside assessment (derived from clinical parameters available prior to lactate measurement).
Secondary analyses
In the subset of patients who developed severe sepsis,
the median time from meeting severe sepsis criteria to
lactate measurement was 75 min (range 01,220). Table 3
presents the subgroup analysis stratifying patients by
hospital location. For the majority (60%) of patients in
the study who had initial lactate measured in the ED,
a lactate 4.0 mmol/l was associated with similar odds
ratios for both acute-phase and in-hospital death (3.0
and 3.2 respectively). In the ICU population, an initial
lactate 4.0 mmol/l was most useful in the prediction of
acute-phase death (odds ratio 7.4). The highest odds ratios
for death in the sample were observed in the minority
(18%) of patients from a non-ICU ward, although lactate
values above 4 mmol/l were relatively uncommon in this
subgroup.

Discussion
In patients with infection [1] and in heterogeneous populations of patients with sepsis [25] elevation in serum
lactate concentration has been associated with increased
risk of death. Guidelines from the SSC endorsed by 11
medical professional societies including the European

Society of Intensive Care Medicine now advocate lactate

measurement as a screening tool for identifying high risk
of death in patients with suspected severe sepsis [7, 8].
The SSC guidelines are intended to apply to patients with
suspected severe sepsis across all hospital-based practice
settings included in this sample (ED, ICU, and non-ICU
hospital ward). However, the utility of lactate measurement to identify high risk of death when broadly adopted
hospital-wide by clinicians in real world practice was
unclear. Therefore we aimed to determine the utility of
initial serum lactate measurement to identify high risk
of death in infected patients after hospital-wide implementation of the SSC guidelines for measuring lactate
in patients with confirmed infection and possible severe
sepsis.
We found that the probability of acute-phase death and
in-hospital death increased significantly and in a linear
fashion with increasing range of initial lactate values.
Although there are many potential mechanisms for lactate
elevation in sepsis in addition to tissue hypoxia (e.g.,
metabolic derangements) [1820], our data contribute to
the body of evidence that, regardless of the cause of the
lactate generation, lactate elevation can serve as a marker
of high risk of death [1, 2, 4, 5, 21]. Using a cutoff of
4 mmol/l to define a positive test, an initial lactate above
this level was associated with sixfold higher odds of
acute-phase death. We utilized a Bayesian approach to
analysis [11, 12] through a full range of possible pretest
probabilities for death (and graphically represented the
relationships between pre- and posttest probabilities)
(Fig. 3) so that clinicians can see how the use of lactate
level can affect any given pretest probability for death that
may be derived from all other clinical parameters prior

975

to lactate measurement. Figure 3a demonstrates that the

steepest part of the curve (i.e., the range in which lactate
has the greatest capacity to affect probability estimate of
acute-phase death) occurs when a lactate value of 4 mmol/l
or higher is obtained, and the clinicians pretest probability
for death was low. Figure 3b demonstrates that a lactate
value less than 4 mmol/l has little impact on probability
for in-hospital death throughout the full range of potential
pretest probabilities. These curves show the substantial
impact that a lactate of 4 mmol/l or greater can have on
pretest probability for death, especially acute-phase death,
but also suggest that perhaps low lactate values should not
be reassuring to the clinician.
The corollary to the use of a Bayesian approach is that
the importance of lactate measurement cannot be divorced
from a clinicians clinical impression of pretest probability
for death. As lactate is not a black box test that can be
used to predict mortality devoid of other clinical parameters, clinicians should measure lactate to augment, not replace, bedside assessment of mortality risk. This is an important consideration in clinical practice as clinicians are
known to be reluctant to rely solely on risk stratification
tools (such as actuarial mortality prediction models) to predict outcome in individual patients [22]. As the ability of
a lactate value to generate a posttest probability for death is
inherently a function of the clinicians pretest probability
estimate, bedside clinical acumen remains vitally important.
Although contemporary clinical investigations may be
likely to employ new and complex tools (such as novel
severity of illness scoring systems or clinical prediction
rules) to achieve mortality risk stratification in patients
with infection and sepsis, these types of multivariable
indices may be cumbersome for routine use by clinicians
at the bedside. In contrast, lactate measurement has been
available for decades and is a relatively simple test that
most acute care clinicians can easily obtain. One of the
most attractive features of utilizing lactate measurement
to aid in real-world mortality risk stratification in infected
patients may be the simplicity of its use.

Limitations
We recognize limitations in the interpretation of our findings. First, the timing of measuring lactate in relation to the
time that a clinician first identified the presence of an acute
infection was not available for all subjects in this lactate
registry and could only be inferred from a sample of high
severity patients who also developed severe sepsis criteria. This represents an important limitation that could have
potentially introduced some heterogeneity into the sample
with respect to acuity of the infectious process at the time
lactate was measured. However, this concern is attenuated

by the following: (a) the median time from meeting severe sepsis criteria to lactate measurement in the secondary
analysis was only 75 min, and (b) our multidisciplinary education program conducted immediately prior to the study
period instructed all clinicians to obtain a lactate measurement promptly as soon as the possibility of sepsis was first
considered [14].
Second, the fact that this study only included patients
in whom lactate was measured by a clinician represents an
inherent bias in the sample. Although we recognize that
the decision to measure lactate was necessarily dependent
upon a variable level of proficiency with sepsis identification among individual clinicians, we point out that varying clinician proficiencies are an inherent factor in transfer of all guidelines to the bedside. Therefore we would
suggest that this real world experience [23] is the most
informative type of data with regard to implementation of
the SSC lactate guideline. We also recognize that using lactate data that was the product of a clinical decision rather
than measured at a fixed time point in the hospital course
(e.g., hospital admission) may be responsible in part for
a contrast between our results and the results of previous studies that found lactate values upon initial presentation were nondiscriminatory between sepsis survivors and
nonsurvivors [24, 25]. Rather than providing support for
the utility of lactate measurement at a fixed time point in
the hospital course, our data supports the utility of lactate
measurement at the time of initial clinical suspicion of sepsis.
Fourth, this registry did not capture comprehensive
clinical information. Specifically, we do not have data on
the presence of systemic inflammatory response syndrome
criteria at the time of lactate measurement. Therefore
it is unclear how many subjects would have met the
classical consensus definition of sepsis (i.e., infection
plus two or more criteria for the systemic inflammatory
response syndrome (SIRS)) [26]; rather, we utilized the
clinicians action of obtaining a lactate measurement
as a surrogate for clinical suspicion of sepsis for these
patients with a confirmed infection. The registry also
did not capture data on comorbidities, advance directive
status, hemodynamics, organ dysfunction, or therapies
administered, and thus a multivariate analysis could not
be performed. Therefore it is possible that patients with
high lactate values would have also been identified as
having high risk of death by other clinical indicators
independently of lactate measurement. That is why we
performed a Bayesian analysis (Fig. 3) to show how the
utilization of lactate measurement may impact any pretest
probability estimate that can be derived from all other
conventional clinical parameters that are available.
Lastly, we did not capture clinicians estimates for
probability of death prior to obtaining the lactate measurements. This would be a necessary element of a future study

976

specifically designed to confirm the accuracy and practical ment of mortality risk. Specifically, an initial lactate level
utility of the Bayesian approach to mortality prediction of 4 mmol/l or higher can have a substantial impact on
pretest probability of acute-phase ( 3 days) death.
and its capacity to impact clinical practice decisions.
Acknowledgements. The authors thank Tara Haag for her assistance in the preparation of this manuscript. Dr. Trzeciak is supported
Conclusions
by a Scientist Development Grant from the American Heart AssociThere was no outside source of funding for the project costs
When implemented in a multidisciplinary hospital-wide ation.
associated with this study. None of the authors have financial confashion, routine measurement of lactate in patients with flicts of interest to disclose. The authors had full control of the data
infection and possible sepsis can impact clinical assess- and the decision to publish.

References
1. Shapiro NI, Howell MD, Talmor D,
Nathanson LA, Lisbon A, Wolfe RE,
Weiss JW (2005) Serum lactate as
a predictor of mortality in emergency
department patients with infection. Ann
Emerg Med 2 45:524528
2. Aduen J, Bernstein WK, Khastgir T,
Miller J, Kerzner R, Bhatiani A,
Lustgarten J, Bassin AS, Davison L,
Chernow B (1994) The use and clinical
importance of a substrate-specific
electrode for rapid determination of
blood lactate concentrations. JAMA
272:16781685
3. Bakker J (2001) Lactate: may I have
your votes please? Intensive Care Med
27:611
4. Bakker J, Coffernils M, Leon M, Gris P,
Vincent JL (1991) Blood lactate levels
are superior to oxygen-derived variables
in predicting outcome in human septic
shock. Chest 99:956962
5. Bakker J, Gris P, Coffernils M, Kahn RJ,
Vincent JL (1996) Serial blood lactate
levels can predict the development of
multiple organ failure following septic
shock. Am J Surg 171:221226
6. Varpula M, Tallgren M, Saukkonen K,
Voipio-Pulkki LM, Pettila V (2005)
Hemodynamic variables related to
outcome in septic shock. Intensive Care
Med 31:10661071
7. Dellinger RP, Carlet JM, Masur H,
Gerlach H, Calandra T, Cohen J,
Gea-Banacloche J, Keh D, Marshall JC,
Parker MM, Ramsay G, Zimmermann JL, Vincent JL, Levy MM
(2004) Surviving Sepsis Campaign
guidelines for management of severe
sepsis and septic shock. Crit Care Med
32:858873

8. Dellinger RP, Carlet JM, Masur H,

Gerlach H, Calandra T, Cohen J,
Gea-Banacloche J, Keh D, Marshall JC,
Parker MM, Ramsay G, Zimmermann JL, Vincent JL, Levy MM (2004)
Surviving Sepsis Campaign guidelines
for management of severe sepsis and
septic shock. Intensive Care Med
30:536555
9. Rivers E, Nguyen B, Havstad S,
Ressler J, Muzzin A, Knoblich B,
Peterson E, Tomlanovich M, Early
Goal-Directed Therapy Collaborative
Group (2001) Early goal-directed
therapy in the treatment of severe
sepsis and septic shock. N Engl J Med
345:13681377
10. Levy MM, Pronovost PJ, Dellinger RP,
Townsend S, Resar RK, Claemmer TP,
Ramsay G (2004) Sepsis change
bundles: converting guidelines into
meaningful change in behavior and
clinical outcome. Crit Care Med
32:S595597
11. Marcin JP, Pollack MM, Patel KM, Ruttimann UE (2000) Combining physicians subjective and physiology-based
objective mortality risk predictions. Crit
Care Med 28:29842990
12. Brannen AL 2nd, Godfrey LJ, Goetter WE (1989) Prediction of outcome
from critical illness. A comparison of
clinical judgment with a prediction rule.
Arch Intern Med 149:10831086
13. Abate NL, Stauss M, Baumann B, Trzeciak S (2004) Using a multidisciplinary
acute sepsis initiative to teach early
goal-directed therapy for sepsis-induced
hypoperfusion states. Ann Emerg Med
44:76S
14. Dellinger RP on behalf of the Surviving
Sepsis Campaign (2004) The Surviving
Sepsis Campaign guidelines. Presented
at the 33rd Annual Congress of Society
of Critical Care Medicine, Orlando

15. Trzeciak S, Dellinger RP, Abate NL,

Cowan RM, Stauss M, Kilgannon JH,
Zanotti S, Parillo JE (2006) Translating
research to clinical practice: a 1-year
experience with implementing early
goal-directed therapy for septic shock
in the emergency department. Chest
129:225232
16. Angus DC, Linde-Zwirble WT,
Lidicker J, Clermont G, Carcillo J,
Pinsky MR (2001) Epidemiology of
severe sepsis in the United States:
analysis of incidence, outcome, and
associated costs of care. Crit Care Med
29:13031310
17. Surviving Sepsis Campaign (2005)
Implementing the surviving sepsis
campaign. Society of Critical Care
Medicine, European Society of Intensive Care Medicine, and International
Sepsis Forum, Des Plaines
18. James JH, Luchette FA, McCarter FD,
Fischer JE (1999) Lactate is an unreliable indicator of tissue hypoxia in
injury or sepsis. Lancet 354:505508
19. Luchette FA, Jenkins WA, Friend LA,
Su C, Fischer JE, James JH (2002)
Hypoxia is not the sole cause of lactate
production during shock. J Trauma
52:415419
20. Di Giantomasso D, Bellomo R,
May CN (2005) The haemodynamic
and metabolic effects of epinephrine
in experimental hyperdynamic septic
shock. Intensive Care Med 31:454462
21. Meregalli A, Oliveira RP, Friedman G
(2004) Occult hypoperfusion is associated with increased mortality in
hemodynamically stable, high-risk,
surgical patients. Crit Care 8:R60R65
22. The SUPPORT Principal Investigators
(1995) A controlled trial to improve
care for seriously ill hospitalized
patients. The study to understand prognoses and preferences for outcomes and
risks of treatments (SUPPORT). JAMA
274:15911598

977

23. Rivers EP (2006) Early goal-directed

therapy in severe sepsis and septic
shock: converting science to reality.
Chest 129:217218
24. Duke TD, Butt W, South M (1997)
Predictors of mortality and multiple
organ failure in children with sepsis.
Intensive Care Med 23:684692

25. Friedman G, Berlot G, Kahn RJ,

Vincent JL (1995) Combined measurements of blood lactate concentrations
and gastric intramucosal pH in patients
with severe sepsis. Crit Care Med
23:11841193

26. American College of Chest Physicians/Society of Critical Care Medicine

Consensus Conference (1992) Definitions for sepsis and organ failure and
guidelines for the use of innovative
therapies in sepsis. Crit Care Med
20:864874