Emergency Medicine Australasia (2017) 29, 626–634 doi: 10.1111/1742-6723.

12894

ORIGINAL RESEARCH

Lactate ≥2 mmol/L plus qSOFA improves utility over

qSOFA alone in emergency department patients
presenting with suspected sepsis
Amith SHETTY ,1,2 Stephen PJ MACDONALD ,3,4,5 Julian M WILLIAMS,6 John van BOCKXMEER,7
Bas de GROOT,8 Laura M ESTEVE CUEVAS,9 Annemieke ANSEMS,9 Malcolm GREEN,10
Kelly THOMPSON,11 Harvey LANDER,10 Jaimi GREENSLADE ,6,12 Simon FINFER11 and Jonathan IREDELL1
1
Westmead Institute for Medical Research, NHMRC Centre for Research Excellence in Critical Infection, Sydney, New South Wales, Australia,
2
Westmead Emergency Medical Research Unit, Westmead Hospital, Sydney, New South Wales, Australia, 3Centre for Clinical Research in
Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia, 4Department of Emergency Medicine, Royal
Perth Hospital, Perth, Western Australia, Australia, 5Division of Emergency Medicine, The University of Western Australia, Perth, Western Australia,
Australia, 6Department of Emergency Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia, 7Western Australia Country
Health Service, South Hedland, Western Australia, Australia, 8Department of Emergency Medicine, Leiden University Medical Centre, Leiden, The
Netherlands, 9Emergency Department, Albert Schweitzer Ziekenhuis, Dordrecht, The Netherlands, 10Clinical Excellence Commission, Sydney, New
South Wales, Australia, 11Critical Care and Trauma Division, The George Institute for Global Health, Sydney, New South Wales, Australia, and
12
Department of Biostatistics, Queensland University of Technology, Brisbane, Queensland, Australia

Abstract Australia and The Netherlands. Key findings

Patients are identified as candidates for
Objective: The Sepsis-3 task force rec- quality improvement initiatives or • The Sepsis-3 task force recom-
ommends the use of the quick Sequen- research studies at respective sites based mends the use of qSOFA score
tial Organ Failure Assessment (qSOFA) on local screening procedures. Data- ≥2 to identify risk for adverse
score to identify risk for adverse out- sharing was performed across sites of
outcomes in patients with sus-
comes in patients presenting with sus- demographics, qSOFA, SOFA, lactate
thresholds and outcome data for pected sepsis, though recent
pected infection. Lactate has been
shown to predict adverse outcomes in included patients. LqSOFA(2) scores evaluations have revealed a low
patients with suspected infection. The were calculated by adding an extra sensitivity for this tool.
aim of the study is to investigate the point to qSOFA score in patients who • The addition of lactate ≥2
utility of a post hoc lactate threshold met lactate thresholds of ≥2 mmol/L. mmol/L threshold as an addi-
(≥2 mmol/L) added qSOFA score Results: In a merged dataset of 12 555 tional point with derivation of
(LqSOFA(2) score) to predict primary patients where a full qSOFA score and the LqSOFA score ≥2 improves
composite adverse outcomes (mortality outcome data were available,
the sensitivity in identifying
and/or ICU stay ≥72 h) in patients pre- LqSOFA(2) ≥2 identified more patients
with an adverse outcome (sensitivity adverse outcomes to 65.5% in
senting to ED with suspected sepsis.
65.5%, 95% confidence interval 62.6– patients with suspected sepsis.
Methods: Retrospective cohort study
was conducted on a merged dataset of 68.4) than qSOFA ≥2 (sensitivity • Future ED studies focusing on
suspected or proven sepsis patients pre- 47.6%, 95% confidence interval 44.6– rapid sepsis adverse outcome
senting to ED across multiple sites in 50.6). The post hoc addition of lactate screening tools with improved
performance characteristics
Correspondence: Dr Amith Shetty, Westmead Emergency Medical Research Unit, could lead to improved resource
Emergency Department, Westmead Hospital, Corner Darcy and Hawkesbury Roads, allocation and risk stratification
Westmead, NSW 2145, Australia. Email: amith.shetty@sydney.edu.au of suspected sepsis patients.
Amith Shetty, MBBS, FACEM, Emergency Physician, Honorary Research Fellow; Ste-
phen PJ Macdonald, BSc, MBChB, DCH, FRCP (Edin), FACEM, Emergency Physi-
cian; Julian M Williams, MBBS, FACEM, Emergency Physician; John van Bockxmeer, threshold identified higher proportion
MBBS, FACRRM, FRACGP, Emergency Medical Officer; Bas de Groot, MD, PhD, of patients at risk of adverse outcomes.
Emergency Physician; Laura M Esteve Cuevas, MD, Emergency Physician; Conclusions: The lactate ≥2 mmol/L
Annemieke Ansems, MD, Emergency Physician; Malcolm Green, RN, BN, MN, Senior threshold-based LqSOFA(2) score per-
Manager; Kelly Thompson, RN, BN, MPH, Senior Clinical Research Associate; forms better than qSOFA alone in
Harvey Lander, MBBS, FRACMA, MBA, Director Systems Improvement; identifying risk of adverse outcomes
Jaimi Greenslade, PhD, Research Fellow, Associate Professor; Simon Finfer, MBBS, in ED patients with suspected sepsis.
FRCA, FRCP, FCICM, FAHMS, DrMed, Professorial Fellow; Jonathan Iredell, MBBS,
PhD, FRACP, FRCPA, FFScRCPA, Director. Key words: algorithm, critical care,
Accepted 4 October 2017 lactic acid, mortality, sepsis.

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
LACTATE PLUS QUICK SOFA SCORE IN SUSPECTED SEPSIS
Introduction
Background
Sepsis is a life-threatening organ dys-
function caused by a dysregulated
host response to infection. It is
defined as an infection-related
increase in Sequential (sepsis-related)
Organ Failure Assessment (SOFA)
score of two points or more from
baseline.1 The Sepsis-3 working
group used a combined adverse
event (AE) (prolonged ICU stay
≥72 h or death in hospital) as a
marker of adverse outcomes that are
typical of sepsis rather than uncom-
plicated infection. The task force
also developed a rapid bedside tool,
the quick SOFA (qSOFA) measure,1
based on three criteria: altered men-
tation, systolic blood pressure of
100 mmHg or less and respiratory
rate of 22 breaths/min or greater.
The presence of two or more qSOFA
criteria was found to have predictive
utility similar to the full SOFA score
for detecting sepsis in out-of-hospital
and ED settings and was suggested
for use as a prompt for consideration
of sepsis among patients presenting
with suspected infection.2 Several
recent studies have focused on the
prognostic accuracy of the qSOFA
score,3–5 generally reporting high
specificity but low sensitivity. These
findings would be consistent with a
primary role for qSOFA as a severity
marker rather than a screening tool.6
Elevated lactate is associated with
an increased risk of adverse out-
comes for patients with sepsis,7,8 and
past studies have also shown a
higher risk for adverse outcomes
associated with hyperlactatemia than
with refractory hypotension.9 Serum
lactate did not meet statistical
thresholds for inclusion in qSOFA
model construction, which the
Sepsis-3 task force suggest may be
due to variable lactate measurement
rate within cohorts. The Sepsis-3
task force also recommended assess-
ment of serum lactate levels for
patients with borderline qSOFA
values, and suggest a serum lactate
level of 2 mmol/L or higher may per-
form well as a substitute for individ-
ual qSOFA variables, when this can
be measured at low cost and in a
timely manner.2
© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
627
Objectives and SOFA-based organ dysfunction
in a cohort of patients identified
We hypothesised that the addition of
daily in the ED with diagnoses
lactate to the qSOFA score would
related to presumed or potential
improve its sensitivity for adverse
infection. The most abnormal physi-
outcomes, and therefore improve
ological parameter during the ED
utility of the score as a risk-
stay was recorded in the dataset and
stratifying tool. We investigated the
investigation results were obtained
addition of lactate threshold
through hospital databases,3 with
≥2 mmol/L to qSOFA score for pre-
the approval of the RBWH Research
diction of the composite AE outcome
Ethics Committee.
of in-hospital death or ICU stay
The Sydney Multicentre Emer-
≥72 h. We secondarily aimed to
gency Department Sepsis Archive
investigate the performance of
(SMEDSA) was designed as an
qSOFA ≥2 threshold when the GCS
embedded quality research initiative
variable was replaced by the lactate
at four participating ED sites, fol-
≥2 mmol/L.
lowing the implementation of the
NSW state-wide (SIRS algorithm-
based) SEPSIS KILLS programme.10
Materials and methods Initial SIRS variables and investiga-
Study design, setting and tion results in ED were recorded
participants through retrospective chart reviews
based on the time of identification of
A retrospective cohort study was
the sepsis event. Specific approval
performed on a merged dataset cre-
was obtained from the Western Syd-
ated from existing datasets from six
ney Local Health District Human
Australian EDs (The AUSMEDS col-
Research Ethics Committee.
laborative) and three Dutch hospi-
The Critical Illness and Shock Study
tals. Adult patients (age 18 years and
(CISS) is a prospective observational
older in Australia and 16 years and
study of patients who meet a pre-
older than 16 years in The Nether-
specified definition for critical illness
lands) with suspected infection, sus-
in two EDs in Perth, Western
pected or confirmed sepsis, based on
Australia, recruited during research
locally applied systemic inflamma-
staff hours. Participants undergo clini-
tory response syndrome (SIRS)
cal data collection and blood sam-
screening algorithms, were included.
pling, and follow-up for clinical
Patients were identified as candidates
outcomes of interest. The cohort
for quality improvement initiatives
reported here is a subset with sepsis,
or research studies at respective sites
defined as presence of two or more
based on local screening procedures.
SIRS criteria, administration of
Brief details on settings, selection of
i.v. antibiotics and admission with a
participants, periods of patient
diagnosis consistent with infec-
recruitment and data collection
tion.12,14 The present study is
methods are briefly described below
approved by the Royal Perth Hospital
and in Table 1, with details
Human Research Ethics Committee.
described elsewhere.3,10–13
The Audit of Sepsis at Hedland
A state-wide multicentre ED dataset
(ASH) study is a retrospective study
from New South Wales (NSW) Clini-
in patients presenting to a remote ED
cal Excellence Commission (CEC)
in Western Australia with a diagnosis
Sepsis register was used to analyse the
of sepsis resulting in tertiary hospital
performance of a modified LqSOFA
transfers for ICU management or in-
score (GCS values missing).
hospital deaths. Ethical approval for
the study was granted by the Western
Australia Country Health Service
Variables and data collection
Human Research Ethics Committee
procedures as a retrospective chart audit.
The Royal Brisbane and Women’s The Netherlands ED sepsis (Sepsis
Hospital (RBWH) observational op Spoedeisende Hulp [SOS]) study
database was originally designed to was a prospective observational
examine the performance of SIRS study conducted at three EDs
 628

TABLE 1. Study settings, participants, period of patient recruitment, data collection methods and ethics review board details for the AUSMEDS collaborative
RBWH SMEDSA CEC† CISS ASH SOS
(QLD, Australia) (NSW, Australia) (NSW, Australia) (WA, Australia) (WA, Australia) (The Netherlands)

Settings Single tertiary referral Single tertiary referral State-wide registry Two tertiary referral Remote ED at Hedland Three EDs in The
metropolitan ED metropolitan and single including 97 EDs metropolitan hospital Health Campus Netherlands ongoing
district hospital ED EDs in Perth quality improvement
programme
Participants Patients admitted from Patients placed on sepsis Patients placed on sepsis Critically unwell ED ED patients with a ED patients with
ED with suspected pathway based on SIRS pathway based on SIRS patients meeting diagnosis of severe suspected infection
infection criteria and/or clinician criteria physiological criteria sepsis with an adverse with urgent triage
suspicion of sepsis for shock or organ outcome (death, category and receiving
failure excluding those transfer, ICU i.v. antibiotics in the
with non-sepsis admission) during the ED
diagnosis study period
Period of October 2007 to January 2013 to January 2012 to March 2010 to July 1 January 2012 to 1 June 2011 to 1 June
recruitment (data December 2008 and December 2014 and December 2013 2013 31 December 2016 2014 at LUMC;
records included for June 2009 to May January 2016 to (n = 12 349) (n = 40) 1 March 2012 to
current analyses) 2011 (n = 8871) December 2016 1 April 2013 at RH;
(n = 1274) 1 September 2015 to
1 November 2015 in
the ASZ
Data collection Retrospective audit of Retrospective audit of Voluntary prospective Real-time clinical data Retrospective chart Retrospective audit of
prospectively identified prospectively identified and retrospective data. collection and repeated (HCare and webPAS prospectively identified
ED patients with ED patients with Health outcomes data blood sampling by electronic management ED patients with
suspected infection suspected infection linkage by Centre for trained research nurses systems) audit of suspected infection
audits and in-hospital Health Record Linkage over the initial 24 h of 40 eligible patients
outcomes (CHeReL) their hospital stays during study period
with diagnosis of sepsis
qSOFA/SIRS/SOFA The most abnormal Based on observations Based on observations The most abnormal Based on observations at Calculated at the initial
point in time analysis physiological upon entry to sepsis upon entry to sepsis physiological initiation of i.v. fluid or time point at initiation
parameters recorded in pathway pathway parameters recorded antibiotic therapy for of therapy
ED during in ED sepsis

†CEC dataset not included in merged analysis. ASH, Audit of Sepsis in Hedland, Western Australia; ASZ, Albert Schweitzer Hospital; CEC, Clinical Excellence Commis-
sion; CISS, Critical Illness and Shock Study; LUMC, Leiden University Medical Centre; qSOFA, quick Sequential Organ Failure Assessment score; RBWH, Royal Brisbane
and Women’s Hospital; RH, Rijnstate Hospital; SIRS, systemic inflammatory response syndrome; SMEDSA, Sydney Multicentre Emergency Department Sepsis Archive;
SOFA, Sequential (sepsis-related) Organ Failure Assessment score; SOS, Sepsis op Spoedeisende Hulp.
A SHETTY ET AL.

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
LACTATE PLUS QUICK SOFA SCORE IN SUSPECTED SEPSIS 629

TABLE 2. Sepsis and severity score definitions utilised across datasets for AUSMEDS quick Sequential Organ Failure
Assessment (qSOFA) validation study
Systemic inflammatory Sequential (sepsis-related) qSOFA (0–3)† Lactate threshold-enhanced
response syndrome (range 0–4 Organ Failure Assessment qSOFA score (LqSOFA(2))
criteria)† (SOFA) score (range 0–24)† (range 0–4)†

Tachypnoea respiratory rate
>20 or PaCO2 <32
Abnormal white blood cell
count (>12 000/μL or
<4000/μL or >10%
immature [band] forms)
Heart rate of more than
90/min
Fever of more than 38 C or
less than 36 C
PaO2/FiO2 or SaO2/FiO2 Respiratory rate, breaths qSOFA score + one point for
ratio16 per minute ≥22 lactate ≥2 mmol/
GCS score GCS score <15 L = LqSOFA(2) score
Mean arterial pressure, mmHg Systolic blood pressure
≤100 mmHg
Administration of vasopressors
with type/dose/rate of
infusion
Serum creatinine, mg/dL; or
urine output, mL/day
Bilirubin, mg/dL
Platelet count, 109/L

†Normal data value substitution conducted in case of missing data variable as is standard in clinical risk score
calculation.

(Leiden University Medical Centre in
Leiden, the Rijnstate Hospital in
Arnhem and the Albert Schweitzer
Hospital in Dordrecht). All ED
patients >16 years old with a sus-
pected infection and Manchester tri-
age category yellow, orange or red
(constituting those with urgent medi-
cal needs) who received i.v. antibiotics
in the ED and were subsequently hos-
pitalised were included in the study
population.13
The NSW CEC Sepsis register was
set up through linkage of SEPSIS
KILLS programme data at multiple
ED sites with state-wide registries for
discharge diagnosis and outcomes,
undertaken by the Centre for Health
Record Linkage for NSW Health.
The NSW Sepsis Register was devel-
oped as a public health and disease
register under section 98 of the Pub-
lic Health Act 2011.11 GCS and
investigation results (excluding lac-
tate values) were not collected on the
register and thus a qSOFA score
excluding one point for GCS <15
was calculated for the cohort (total
qSOFA score 0–2).
The study site settings, data collec-
tion procedures, recruitment periods
and data definitions used for the cur-
rent study are outlined in Tables 1
and 2.
Definitions
The SIRS, qSOFA and SOFA scores
were calculated on individual data-
sets at corresponding sites, accord-
ing to protocols in Table 1 and
using criteria in Table 2. Missing
data variables were imputed with
normal value substitution as is now
standard in clinical risk score calcu-
lations.15 To the qSOFA score
(range 0–3), a point was added for
serum lactate ≥2 mmol/L to develop
a LqSOFA(2) score (range 0–4). In
the SOS cohort, altered mental sta-
tus and/or clinical signs of delirium
data were used to substitute a full
GCS value (3–15), which was una-
vailable. A modified SOFA score
was calculated in the SOS dataset by
assigning a SOFA (central nervous
system) score of 1 for all patients
with altered mentation. Individual
sites were responsible for calculation
of scores and data was shared in de-
identified format for merged analysis
at a single site.
In the CEC dataset where no GCS
values were available, a qSOFA
score was calculated with a range of
0–2 and LqSOFA(2) scores from 0–3.
Due to lack of GCS data in the CEC
dataset (n = 12 349), this dataset was
not included in the merged dataset.
Statistical analysis
Area under receiver operating char-
acteristic curves (AUROC) for each
score were calculated for the com-
posite AE outcome. AUROC were
calculated both on individual data-
sets and the merged AUSMEDS
dataset.17 Test performance statistics
at pre-defined threshold of ≥2 (sensi-
tivity/specificity, predictive values,
relative risk and odds ratios) were
conducted on a merged dataset for
SOFA, qSOFA and LqSOFA(2)
scores. AUROC and test perfor-
mance analysis were performed only
on the LqSOFA(2) ≥2 threshold on
the CEC dataset. MedCalc Statistical
Software version 17.5 (MedCalc

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
630
Software bvba, Ostend, Belgium)
was used to conduct the statistical
analysis.
Results
Demographics
Patient characteristics and demo-
graphics data are reported in
Table 3. Mortality rates ranged from
2.9% (95% confidence interval
[CI] 2.5–3.2) in the RBWH cohort
of all patients with suspected infec-
tion to 30% (95% CI 18.1–45.4) in
the ASH cohort of confirmed severe
sepsis patients. The composite
adverse outcome rates ranged
between 4.7% (95% CI 4.3–5.2) in
the RBWH dataset to 92.5% (95%
CI 80.1–97.4) in the Western Aus-
tralia Country Health Service
patients. The overall mortality in the
AUSMEDS cohort (n = 12 555) was
4.6% (n = 572, 95% CI 4.2–4.9) and
the primary AE occurred in 8.6%
(n = 1076, 95% CI 8.1–9.1).
SOFA ≥2, qSOFA ≥2 and
LqSOFA(2) ≥2 threshold
comparisons for AE in the
AUSMEDS dataset
In the merged dataset of 12 555
patients, the SOFA ≥2 score showed
the highest predictive validity for pri-
mary AE of mortality or prolonged
ICU stay (≥72 h) (area under curve
[AUC] 0.75, 95% CI 0.74–0.76,
P < 0.001; sensitivity 85.9%, 95%
CI 83.6–87.9%). The LqSOFA(2) ≥2
had a higher predictive validity
(AUROC 0.74 [0.73–0.74] vs 0.68
[95% CI 0.68–0.69]) and sensitivity
than qSOFA ≥2 (65.5% [95% CI
62.6–68.4] vs 47.6% [95% CI
44.6–50.6]) for primary AE out-
come. Other test performance statis-
tics comparing qSOFA ≥2 and
LqSOFA(2) ≥2 thresholds to the
recently promulgated sepsis defini-
tion threshold of SOFA ≥2 are out-
lined in Table 4.
LqSOFA(2) ≥2 rule performance
in the CEC dataset
In the CEC dataset, where the GCS
values of patients were not available
for analysis, the LqSOFA(2) ≥2
© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
threshold had a lower predictive
value and sensitivity for AE outcome
(AUC 0.62, 95% CI 0.61–0.63, and
40.8, 95% CI 38.0–43.5) when com-
pared to qSOFA ≥2 threshold (AUC
0.68, 95% CI 0.68–0.69, and 47.6,
95% CI 44.6–50.6) in the SMEDSA
cohort, which used similar entry cri-
teria for study subject inclusion
(Table 5).
Lactate addition at borderline
qSOFA score
In the merged dataset of 12 555
patients, 10 786 (85.9%) patients
did not meet the qSOFA ≥2 thresh-
old. In this cohort of qSOFA nega-
tive patients, the addition of lactate
≥2 mmol/L threshold flagged 1056
(8.4% of complete cohort) more
patients, of whom 193 patients
(18.3%, 95% CI 16.1–20.7) met the
primary AE outcome.
Discussion
On a merged dataset of 12 555
patients from multiple EDs in
Australia and The Netherlands, post
hoc addition of lactate ≥2 mmol/L
cut-off to the qSOFA score resulted
in improved sensitivity for identify-
ing patients at risk for mortality or
prolonged ICU stay. Our study
found poor sensitivity for the qSOFA
score, which is in keeping with
recent prospective evaluations.18,19
As our study consisted of patients
presenting to the ED early in their
course of illness, and most sites had
sepsis management bundles in situ,
the composite adverse outcome mea-
sure (mortality and/or prolonged
ICU stay) was a more suitable end-
point for the study rather than mor-
tality alone similar to those utilised
to identify patients more likely to
have with sepsis outcomes.1
Screening tests aim to discover
latent disease among the apparently
well.20 Clinical scores and classifica-
tion systems, in contrast, support
decision-making and management,
enabling the clinician to stratify risk
for adverse outcomes in diseased
populations.21 Selective screening of
high-risk groups in hospitals or other
healthcare settings may be used to
select patients requiring more
A SHETTY ET AL.
complex investigations and manage-
ment.20 Flagging of patients with
high risk for adverse outcomes
among patients presenting with sus-
pected infection results in increased
investigation, monitoring and
aggressive therapies, including
broad-spectrum antibiotics. Risk
stratification tools with high sensitiv-
ity and low specificity can thus lead
to inappropriate allocation of
resources, while tools with low sensi-
tivity can lead clinicians to lack trust
in them. Past studies have depicted
wide global variations in severe sep-
sis screening tools and their perfor-
mances10 and also suggested
clinician gestalt as a suitable substi-
tute.22 Our study suggests that the
LqSOFA(2) ≥2 threshold may provide
a uniform approach to sites where
sepsis bundles with SIRS screening
tools and lactate measurements are
already mandated. The challenge in
the diagnosis of sepsis in ED is two-
fold: first identifying patients at risk
of infection and second those who
are at risk of adverse outcomes. The
study sites involved had specific pro-
cedures to address both these criteria
and future studies should focus on
both these aspects of sepsis screen-
ing, rather than on selective screen-
ing of patients with suspected
infection (Fig. 1).
In the cohort of patients in whom
the GCS data were missing, our find-
ings suggest that a lactate ≥2 mmol/L
was a reasonable substitute, but the
LqSOFA(2) ≥2 threshold did not
meet similar performance to the full
qSOFA score. This is in keeping with
findings reported by Seymour et al.2
Sites using screening algorithms that
omit altered GCS or level of con-
sciousness should consider monitor-
ing the performance of their
algorithms in light of these findings.
Our study included a merged data-
set of patients with suspected infec-
tion (RBWH), suspected sepsis
(SMEDSA and SOS) and confirmed
sepsis patients (CISS and ASH). Our
cohort of patients thus represents a
group with an inherent higher risk
for adverse outcome than the general
population of patients with sus-
pected infection. For diseases with a
high risk for adverse outcome, sys-
tems that are highly sensitive aim to
 TABLE 3. Demographic data with systemic inflammatory response syndrome (SIRS) ≥2, Sequential (sepsis-related) Organ Failure Assessment (SOFA) ≥2 and quick SOFA
≥2 prevalence rates on individual datasets
RBWH SMEDSA CEC CISS ASH SOS

Number 8871 1274 12 349 309 40 2370

Males, n (median [IQR]) 4553 (50 [31–69]) 642 (63 [44–76]) 12 349† (72.4 198 (68 [52–78]) 26 (53.5 [42.5–69]) 1364 (66 [54–74])
(years) [58–82.6])
Females, n (median 4318 (47 [28–69]) 632 (56 [34.5–75]) NA 111 (63 [50–75]) 14 (59 [43.8–76]) 1006 (61 [49–72])
[IQR]) (years)
SIRS ≥2, n (% [95% 4176 (47.1 1125 (88.3 [56.4–90]) 3911† (31.7 NA, NC 38 (95% 2131 (89.9
CI]) [46–48.1]) [30.9–32.5]) [83.5–98.6]) [88.6–91.0])
SOFA ≥2, n (% [95% 2784 (31.4 918 (72.1 [69.5–74.5]) NA† 279 (90.3 38 (95.0 [83.5–98.6]) 167 (7.0 [6.1–8.1])
CI]) [30.4–32.4]) [86.5–93.1])
LACTATE PLUS QUICK SOFA SCORE IN SUSPECTED SEPSIS

qSOFA ≥2, n (% [95% 1100 (12.4 289 (22.7 [20.5–25.1]) 682‡ (5.5 [5.1–5.9]) 203 (66 [60–71.2]) 36 (90 [77–96]) 344 (14.5 [13.2–16.0])
CI]) [11.7–13.1])
Lactate (mmol), n (%) 3103 (35) (1.7 1093 (85.8) (1.6 8310 (67.3) (1.9 309 (100) (2.3 35 (87.5) (2.9 2073 (87.4) (1.9
(median [IQR]) [1.2–2.4]) [1.1–2.4]) [1.3–2.9]) [1.5–3.6]) [1.9–5.3]) [1.4–2.6])
Mortality, n 253 (2.9 [2.5–3.2]) 104 (8.2 [6.8–9.8]) 977 (7.9 [7.5–8.4]) 58‡ (18.8 12 (30 [18.1–45.4]) 203§ (8.6 [7.5–9.8])
(% [95% CI]) [14.8–23.5])
Death/ICU ≥72 h rate, 417 (4.7 [4.3–5.2]) 299 (23.5 [21.2–25.9]) 1261 (10.2 [9.7–10.8]) 112 (36.3 37 (92.5 [80.1–97.4]) 323¶ (13.6
n (% [95% CI]) [31.1–41.8]) [12.3–15.1])

†No sex delineation data, white cell counts or SOFA score data available in CEC dataset. ‡30-day mortality data used in CISS dataset. §28-day mortality data used in Lei-
den University Medical Centre dataset. ¶28-day mortality information unavailable for 101 (4.26%) of total cohort of 2370 patients. ASH, Audit of Sepsis in Hedland; CEC,

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Clinical Excellence Commission; CISS, Critical Illness and Shock Study; IQR, interquartile range; NA, not available; NC, not calculated; RBWH, Royal Brisbane and
Women’s Hospital; SMEDSA, Sydney Multicentre Emergency Department Sepsis Archive; SOS, Sepsis op Spoedeisende Hulp.
631
632 A SHETTY ET AL.

TABLE 4. Comparison of test performance statistics for Sequential (sepsis-related) Organ Failure Assessment (SOFA),
quick SOFA (qSOFA) and lactate ≥2 mmol/L plus quick SOFA (LqSOFA(2)) scores at threshold of ≥2 for primary adverse
event outcome (n = 12 555)
Test† SOFA score ≥2 qSOFA score ≥2 LqSOFA(2) score ≥2

AUROC (95% CI) 0.75 (0.74–0.76) 0.68 (0.68–0.69) 0.74 (0.73–0.74)

Sensitivity % (95% CI) 85.9 (83.6–87.9) 47.6 (44.6–50.6) 65.5 (62.6–68.4)
Specificity % (95% CI) 64.5 (63.6–65.3) 89.1 (88.5–89.6) 81.5 (80.8–82.2)
PPV (95% CI) 18.5 (18.0–19.0) 28.9 (27.3–30.6) 25.0 (23.9–26.1)
NPV (95% CI) 98.0 (97.7–98.3) 94.8 (94.5–95.0) 96.2 (95.9–96.5)
Relative risk (95% CI) 2.4 (2.3–2.5) 4.3 (4.0–4.7) 3.5 (3.3–3.8)
NNT (95% CI) 2.0 (2.1–1.9) 2.7 (2.9–2.6) 2.1 (2.2–2.0)
Odds ratio (95% CI) 11.0 (9.2–13.1) 7.4 (6.5–8.4) 8.4 (7.3–9.6)
AE rate below threshold % (95% CI) 2.0 (1.7–2.4) 5.2 (4.8–5.7) 3.8 (3.5–4.2)
AE rate above threshold % (95% CI) 18.5 (17.4–19.6) 28.9 (26.8–3.1) 25.0 (23.4–26.6)

†All results P < 0.001 unless specified. AE, adverse event (defined as mortality and/or prolonged ICU stay ≥72 h);
AUROC, area under receiving operating curve; CI, confidence interval; NNT, number needed to treat; NPV, negative predic-
tive value; PPV, positive predictive value.

TABLE 5. Lactate ≥2 mmol/L plus quick Sequential (sepsis-related) Organ

beyond SIRS screening aimed at
characterising patients who present
Failure Assessment (LqSOFA(2)) score ≥2 threshold performance in Clinical
to ED with suspected infection are
Excellence Commission cohort of patients (n = 12 349) in whom GCS infor-
validated, patients should be selec-
mation was unavailable tively screened based on combina-
Test† LqSOFA(2) score ≥2 tion of current algorithms and
clinician gestalt.
AUROC 0.62 (0.61–0.63) Lactate has been shown to identify
Sensitivity % (95% CI) 40.8 (38.0–43.5) increased risk for adverse outcomes
in the absence of hypotension in
Specificity % (95% CI) 82.7 (82.0–83.4) patients with infection9 and our
PPV (95% CI) 21.1 (19.8–22.4) study confirms its use in identifying
NPV (95% CI) 92.5 (92.1–92.8) patients at risk of adverse outcome.
Our study suggests that until other
Relative risk (95% CI) 2.3 (2.1–2.5) risk stratification tools are validated,
NNT (95% CI) 4.3 (4.9–3.9) patients presenting with suspected
Odds ratio (95% CI) 3.2 (2.8–3.6) infection should undergo lactate test-
ing where this is readily available at
AE rate below threshold (95% CI) 7.5 (7.0–8.1)
the bedside. The use of LqSOFA
AE rate above threshold (95% CI) 21.1 (19.5–22.8) score and LqSOFA(2) ≥2 threshold
will flag more patients at higher risk
†All results P < 0.001 unless specified. AE, adverse event (defined as mortal- for adverse outcomes than qSOFA
ity and/or prolonged ICU stay ≥72 h); AUROC, area under receiving operating alone (Fig. 1). Hyperlactatemia in
curve; NNT, number needed to treat; NPV, negative predictive value; PPV, pos- itself has not been shown to be asso-
itive predictive value. ciated with poor outcomes, espe-
cially in patients with secondary
causes for same.24 While our study
involved patients presenting to ED
identify such patients in EDs and patients who are not selectively with suspected sepsis early in their
inpatient settings.6 Until a robust then screened with qSOFA scoring, journey and involved initial lactate
system for screening patients with lactate measurements or SOFA measurements on presentation, clini-
suspected infection is validated, score calculations at sites with cians should be aware of plausible
SIRS-based screening is likely to con- implemented sepsis management secondary causes of hyperlactatemia
tinue and may continue to miss programmes.23 Until future studies while drawing conclusions on the

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
LACTATE PLUS QUICK SOFA SCORE IN SUSPECTED SEPSIS 633

calculation processes at different

Patients presenting to Emergency departments time points) at participating sites, the
discriminative performance of
LqSOFA was found to be better than
qSOFA alone, indicating that our
Patient cohorts with suspected infection based on
clinical risk factors, SIRS screening algorithms result may be robust and generalisa-
including altered mentation and clinician gestalt ble. The diversity in screening cri-
teria emphasises the need for a
uniform organ dysfunction definition
Bedside lactate measurement where available and qSOFA approach to the research and man-
assessment agement of sepsis, and the develop-
ment of a minimum dataset for
sepsis in the ED to promote future
research and quality endeavours
LqSOFA(2) score ≥ 2 should be a priority.
Close monitoring, further The LqSOFA(2) ≥2 threshold per-
investigation and escalation of
therapy forms better than the qSOFA ≥2
threshold alone in identifying risk
for adverse outcomes in patients
with suspected or proven sepsis
LqSOFA(2) score ≥ 2
Full SOFA score calculation if sepsis still suspected though does not reach sensitivity
and clinical management as appropriate rates to justify its use as a primary
screening tool for patients presenting
Figure 1. Proposed future validation of sepsis screening procedures in EDs. LqSOFA, to ED with suspected sepsis. Future
lactate ≥2 mmol/L plus quick SOFA; SIRS, systemic inflammatory response syndrome;
definitions and research trials involv-
ing patients with suspected sepsis
SOFA, Sequential Organ Failure Assessment.
should consider the inclusion of lac-
tate ≥2 mmol/L thresholds in screen-
ing of patients at risk of adverse
risk stratification based on lactate normal values substitution as is stan- outcomes.
levels alone. dard in calculation of severity
Our study suggests that SOFA ≥2 scores15 for calculation of the
threshold performed best in flagging LqSOFA score. This is a significant
Acknowledgements
patients with suspected infection at limitation of our study and the avail- The authors acknowledge the contri-
risk for adverse outcomes and only ability of these measurements is butions of staff at all collaborating
2% of the cohort (n = 12 555) had a likely to have significant implications sites who contributed to the develop-
SOFA score <2 in ED and suffered on our result. As datasets were ment of original datasets and studies.
an adverse outcome. SOFA score received from individual sites after They also acknowledge the intellec-
involves complex calculations and value substitutions, no conclusions tual contributions from Professor
investigation results, which are often can be drawn upon whether the Glen Arendts (CISS) and other senior
not available in a timely manner dur- cohort of patients with missing lac- advisors at collaborating sites, with-
ing the ED journey of suspected sep- tate values had significantly different out whose guidance and facilitation,
sis patients. Our study suggests that outcomes. It is thus difficult to ascer- the data-sharing agreement and col-
the LqSOFA score is able to predict tain the direction of impact the nor- laboration could not have occurred.
a modest number of patients at risk mal lactate value imputation had on
of adverse outcomes from sepsis the results of our study. The datasets
early in their ED journey. At sites also lacked information around the
Author contributions
where qSOFA flagging is being con- arterial/venous source of lactate mea- AS, JI, SF formulated the concept for
sidered and lactate testing is readily surement. While past studies have the study. AS, SPJM, JMW, JB, HL,
available, the LqSOFA assessment shown strong correlation between MG, BG, AA, LMEC were responsi-
rather than an assessment of qSOFA arterial and venous measurements in ble for data collation and anony-
alone should be prospectively cohorts of patients with sepsis and mous sharing of scoring data with
validated. septic shock,25 large studies compar- the network. AS collated the data
ing these parameters may shed across sites and was responsible for
further light on the interchangeable the analysis for the study. AS, SPJM,
Limitations and strength use of lactate measurements in JMW, JB, MG drafted the initial
Lactate measurements were missing LqSOFA algorithms. manuscript and all authors contrib-
in 47.3% of patients in our merged Despite heterogeneity of recruit- uted significantly through editorial
cohort. In these patients, a lactate ment criteria, variability in data col- input on the manuscript through its
value <2 mmol/L was imputed with lection procedures (qSOFA or SOFA iterations.

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
634
Competing interests
SPJM is a section editor for Emer-
gency Medicine Australasia.
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