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Sepsis Updates

The Third International

Consensus ( 2016 )

Sepsis 3
Dr. Ashraf Nadeem
MD , Critical Care Medicine
Head of ICU
Hafr Elbatin Central Hospital
Saudi Arabia

The Rory story !!!

In March 2012, Rory Staunton,
a 12-year-old boy in Queens,
New York, cut his arm playing
basketball in school. The next
day, his parents, worried about
his fever and leg pain, took him
to see his pediatrician and then,
the day after, to the emergency
department at Langone Medical
Center. He was discharged with
a diagnosis of an upset stomach
and dehydration but died 3 days
later from sepsis

An infection , unnoticed ,
turn Unstoppable

Key Concepts of Sepsis

Sepsis is the primary cause of death from infection,
especially if not recognized and treated promptly.
Its recognition mandates urgent attention.
Sepsis is a syndrome shaped by pathogen factors
and host factors (eg, sex, race and other genetic
determinants, age, comorbidities, environment)
with characteristics that evolve over time.
What differentiates sepsis from infection is an
aberrant or dysregulated host response and the
presence of organ dysfunction.

Key Concepts of Sepsis

Sepsis-induced organ dysfunction may be occult;
therefore, its presence should be considered in
any patient presenting with infection.
Conversely, unrecognized infection may be the
cause of new-onset organ dysfunction.
Any unexplained organ dysfunction should thus
raise the possibility of underlying infection.

Key Concepts of Sepsis

The clinical and biological phenotype of sepsis
can be modified by preexisting acute illness,
long-standing comorbidities, medication, and
Specific infections may result in local organ
dysfunction without generating a dysregulated
systemic host response.

Why Sepsis again !!

Why new definitions !!
Why new scoring system !!

Why Sepsis is revisited again !!!

It is still an economic burden on public health
$ 20 billion of total US hospital cost 2011 (Torio et
Saudi Arabia ???

Sepsis is the leading cause of death in noncoronary care intensive care units, with a
mortality rate between 30-50%

Why Sepsis is revisited again !!!

From 2007 to 2009 , over 2,047,038 patients
were admitted with a sepsis-related illness
54% are diagnosed in the ED
34% on the hospital wards
13% in the ICU

Hospitalization rates

Incidence and Cost

Why Sepsis again !!

Why new definitions !!
Why new scoring system !!

The old definitions

Why new definitions

Definitions of sepsis and septic shock were last
revised in 2001. Considerable advances have
since been made into the pathobiology
(changes in organ function, morphology, cell
biology, biochemistry, immunology, and
circulation), management, and epidemiology of
sepsis, suggesting the need for reexamination.

Why new definitions !!

To know what distinguishes sepsis from
uncomplicated infection as simple infection
(which could simply controlled by rest and cup
of hot tea!! ) SIRS criteria basically could be the
We need to differentiate a straightforward
infection from one that can cause organ
dysfunction or death

The overlap SIRS, infection, sepsis and


Why Sepsis again !!

Why new definitions !!
Why new scoring system !!

The Validity of SIRS challenged

SIRS criteria have been used to diagnose sepsis
for more than 20 years.
SIRS no longer has any legs .. It sounded like
a good idea in 1990 , but it has lost steam..
Poor concurrent Validity

SIRS Criteria
Two or more of:
Temperature >38C or <36C
Heart rate >90/min
Respiratory rate >20/min or PaCO2 <32 mm Hg
(4.3 kPa)
White blood cell count >12000/mm3 or
<4000/mm3 or >10% immature bands
Bone et al.Crit Care Med. 1992;20(6):864-874.

Sequential [Sepsis-Related] Organ Failure

Assessment Score

"We now have a scientifically based classification

that will give the clinician at the bedside new and
more effective ways to recognize the septic
patient and the severely septic patient so as to
afford the earliest possible intervention,"
Timothy Buchman, MD, from Emory University in Atlanta

The care in sepsis is focused on prompt recognition and early

treatment. Shift of focus from inflammation to Organ Dysfunction

This is one of the largest collaborative studies
ever conducted in the field of critical care
medicine. It is also one of the first studies of
electronic health records in field of Intensive

Focused primarily on patients in the intensive
care unit who were receiving antibiotics and
fluid cultures, as those were the patients who
were thought to be infected.
The team analyzed 148,907 patients with
suspected infection, and evaluated how well the
existing and the new criteria predicted sepsis
mortality in these patients.

The Process of Developing New Definitions

A task force of 19 critical
care, infectious disease,
surgical, and pulmonary
specialists in January
The group engaged in
iterative discussions via
face-to-face meetings
between January 2014
and January 2015

The co-chairs
Drs Deutschman & Singer)

The process
Definitions and clinical criteria were generated
through meetings, Delphi processes, analysis of
electronic health record databases, and voting,
followed by circulation to international
professional societies, requesting peer review
and endorsement (by 31 societies listed in the

Summary of Data Sets

Accrual of Encounters for Primary Cohort

What clinical criteria to study

New definitions ( the screening tool )

Patients with suspected infection who are likely to
have a prolonged ICU stay or to die in the hospital
can be promptly identified at the bedside with
Respiratory rate 22/min
Altered mentation
Systolic blood pressure 100mmHg
The presence of at least two of these criteria
strongly predicts the likelihood of poor outcome
in out-of-ICU patients with clinical suspicion of

New definitions
Sepsis is defined as life-threatening organ
dysfunction caused by a dysregulated host
response to infection.
The SIRS criteria have been removed
It may present in simple, non-complicated infection, or
in response to non infectious-triggers (i.e. trauma,
pancreatitis, post-cardiac arrest syndrome),
Or may even be absent in critically ill patients with
obvious evidence of a life-threatening infection.

New definitions
Organ dysfunction can be identified as an acute
change in total SOFA score> 2 points consequent to
the infection.
A SOFA score > 2 reflects an overall mortality risk of
approximately 10% in a general hospital population
with suspected infection
The baseline SOFA score can be assumed to be zero
or in patients not known to have preexisting organ

New definitions
Septic shock is a subset of sepsis in which
underlying circulatory and cellular/metabolic
abnormalities are profound enough to
substantially increase mortality.
Clinical criteria identifying such condition include the
need for vasopressors to obtain a MAP 65mmHg and
an increase in lactate concentration > 2 mmol/L, despite
adequate fluid resuscitation.
Terms like Severe Sepsis/Septicemia has been removed

Organ Failure Check Best in the ICU, Quick Score Better Elsewhere

In the old criteria for sepsis, the systemic

inflammatory response syndrome score was a
measure of respiratory rate, white blood cell
count, heart rate, and fever.
The sequential organ failure assessment score
( SOFA ) and the logistic organ dysfunction
system score ( LODS ) are more recent criteria.

How well these existing scores for inflammation

and organ dysfunction predicted mortality
compared with the quick score!!!

Analysis of electronic records

The receiver operating characteristic curve
(AUROC) has been assessed to predict the
validity of the different scores.
The quick score was a better predictor of
hospital mortality for patients with suspected
infection who were not in the ICU than for those
in the ICU.

Predictive Validity for Death

Area Under the Receiver Operating Characteristic Curve and

95%Confidence Intervals for In-Hospital Mortality of Candidate
(SIRS, SOFA, LODS, and qSOFA) Among Suspected Infection Encounters
in the UPMC Validation Cohort (N = 74 454)

Which score to use !!

"The SOFA score found patients more likely to
be septic both in and out of the ICU. But it
involves the use of many lab tests and is a bit
For patients not in the ICU, the performance of
Quick SOFA score was similar to that of the
sequential organ failure assessment score.

Infection plus two or more sequential organ
failure assessment points, and the use of quick
sepsis-related organ failure assessment score as
a prompt to identify patients likely to be septic
early on,.

A Need for Sepsis Definitions for the Public

and for Health Care Practitioners
A life-threatening condition that arises when the
bodys response to infection injures its own
Finally, all these new definitions are
recommended for coding and research

Terminology and international classification

of disease Coding

Recommended primary ICD codes


Septic shock

Controversies and limitations

Most data extracted from US database
q SOFA and SOFA can miss occult organ
Specific infections can cause local organ
dysfunction without dysregulated systemic host
Non- availability of lactate measurements in
resource poor settings
Task force focused on adult patients

Operationalization of clinical Criteria identifying

patients with sepsis & septic shock

Fostering future updates.

Despite the unavoidable limits affecting any
definition of syndromes that do not have any
specific diagnostic clinical, imaging, laboratory or
biochemical marker, this new classification
includes the most recent deep understanding of
sepsis biology and stresses the clinical relevance
of organ dysfunction. In addition, similarly to
software updates, the Sepsis-3 definition has
been established with the aim of fostering future

Among ICU encounters with suspected infection, the
predictive validity for in-hospital mortality of SOFA
was not significantly different than the more complex
LODS but was statistically greater than SIRS and
qSOFA, supporting its use in clinical criteria for sepsis.
Among encounters with suspected infection outside of
the ICU, the predictive validity for in-hospital
mortality of qSOFA was statistically greater than SOFA
and SIRS, supporting its use as a prompt to consider
possible sepsis.

Take Home Message

New definitions of sepsis and septic shock are now available.
These rely on the importance of recognizing when an
adaptive and protective host response becomes maladaptive,
impairing organ function.
SIRS criteria may still guide clinicians toward identifying an
ongoing infectious process, but severe sepsis is no longer a
part of the new classification.
Hypotension and lactate level are key points underpinning
the new septic shock criteria, as they reflect metabolic and
cellular abnormalities characterizing the pathobiology of

It took us more than 10 years to understand
sepsis , now we will have to change it all
Is it the final word in sepsis .. ? or the
starting point of discussion and additional
research into this deadly condition
Julie A. Jacob, MA JAMA. 2016;315(8):739-740. doi:10.1001/jama.2016.0736.

Thank you