Organ dysfunction can be scored using the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA), a validated risk stratification
tool for intensive care patients with organ
dysfunction.8 The variables in SOFA include
respiratory function (and mechanical support),
platelet count, bilirubin, blood pressure (and
pressor use), conscious level, creatinine and urine
output. Increasing SOFA points (0–4) for each
organ system relate to increasing abnormality.
Big data analysis showed an increase in the SOFA
score by 2 points or more from the patient’s
normal baseline was associated with >10%
increase in mortality. 3
To aid clinicians in non-intensive care settings,
quick SOFA (qSOFA) can be used to identify
patients with suspected infections who are likely
to have poor outcomes (prolonged stay in
intensive care or death in hospital). 3 qSOFA does
not require any laboratory measurements and
is based on the three simple bedside criteria of
altered mentation (any abnormal Glasgow Coma
Score), systolic blood pressure of 100mmHg or
less, and a respiratory rate of 22/min or greater.
A qSOFA score of two or three was present in 24%
of infected patients, but these patients accounted
for 70% of poor outcomes. 9 Of note, qSOFA is
not designed to be a screening tool and is not
diagnostic of sepsis. 10 Failure to meet two or
more qSOFA criteria should not lead to delays
in investigation or treatment of infection. 3
associated with a mortality of 42.3%, compared
with 25–30% in those with organ dysfunction
with either hyperlactataemia or hypotension
or neither. 13
Pathophysiology
Sepsis is a syndrome with an incompletely
understood pathophysiology, involving both
immunological and non-immunological pathways.
The response of an individual to infection
depends on multiple factors including the
pathogen load and virulence and the host’s
comorbidities, age, genetic composition and
medications. 14 Pro-inflammatory and anti-
inflammatory responses occur simultaneously
and early in sepsis and it has been proposed that
immunosuppression, rather than inflammation,
may be the predominant driving force for the
mortality in sepsis. 15 Non-immune processes
involved in sepsis include modulation of
cardiovascular, autonomic, hormonal, metabolic
and coagulation pathways. 16,17 Organ dysfunction
in sepsis is likely to be caused by several factors
including hypotension, microvascular
abnormalities, damage to vascular endothelium
leading to oedema, and mitochondrial
dysfunction impairing cellular oxygen
utilisation. 18
Diagnosing sepsis
As yet, there is no ‘gold-standard’ diagnostic test
for sepsis. Sepsis is a syndrome that is initially
identified by a constellation of clinical signs and
symptoms in a patient with likely or suspected
infection, and confirmed by evidence of organ
dysfunction and, ideally, formal confirmation
of an infecting pathogen. The Surviving Sepsis
Campaign 19 advocates the taking of blood cultures
prior to the initiation of antibiotic therapy;
however, even when microbiological tests are
performed, culture-positive sepsis is observed in
only 30–40% cases. 20 Novel molecular technologies
will improve the yield though the danger of such
tests is over-sensitivity.
Despite the removal of SIRS criteria from the
definition of sepsis, the use of pyrexia and
neutrophilia should still prompt consideration
of infection, albeit these are non-specific signs.
Indeed, up to 40% of patients initially suspected
of having sepsis turn out to have a non-infectious
condition. 21 The likely initial source of infection
can be identified from a careful history (for
example, dysuria, productive cough), clinical
examination (for example, peritonitis, rash) and
imaging (for example, chest X-ray showing lung
consolidation, computerised topography showing
liver abscess).
A patient can be infected without having
sepsis; therefore evidence of organ dysfunction
must be demonstrated to fulfil the criteria for
sepsis. Hyperlactataemia, while not specific to
sepsis, can help identify patients at risk of poor
outcomes, with higher lactate levels predictive of
higher mortality. 22 However, significant numbers
of septic but normo-lactataemic patients die, so
the absence of an elevated lactate should not
necessarily reassure.
The use of biomarkers in diagnosing sepsis is
the subject of much research. Liu and colleagues
reviewed 60 biomarkers used in the diagnosis of
sepsis, seven of which displayed moderate or
Sepsis definitions in paediatric populations
and in low-income countries
The Sepsis-3 Task Force focussed on adult
patients, using electronic healthcare record data
from patients in high-income countries,
predominantly the USA. 3 Matics and Sanchez-
Pinto adapted and validated a paediatric version
of the SOFA score (pSOFA) with age-adjusted
variables and they found assessment of the
Sepsis-3 definition in critically ill children was
feasible. 11 Rudd and colleagues evaluated the use
of qSOFA in low and middle-income countries.
In nine out of ten cohorts, the qSOFA score
clearly identified infected patients at risk of death
beyond those explained by baseline factors. 12
Staging of sepsis
In the Sepsis-2 definition, sepsis complicated
by organ dysfunction was termed severe sepsis,
which could progress to septic shock, defined a
s “sepsis-induced hypotension persisting despite
adequate fluid resuscitation”. 5 In recognition
that such a continuum model of sepsis was
misleading, the Sepsis-3 task force eliminated the
term ‘severe sepsis’. Under the Sepsis-3 definition,
there are two diagnostic categories; sepsis and
septic shock. 3
Septic shock is defined as “a subset of sepsis in
which particularly profound circulatory, cellular
and metabolic abnormalities are associated with
a greater risk of mortality than with sepsis alone”. 3
Adult patients with septic shock can be identified
using the clinical criteria of “hypotension
requiring vasopressor therapy to maintain a mean
arterial blood pressure of 65mmHg or greater and
having a serum lactate level greater than 2mmol/l
(>18mg/dl) after adequate fluid resuscitation”. 13
The combination of fluid-resistant hypotension
requiring vasopressors and hyperlactataemia is
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