The new international consensus 2016 , Sepsis 3

1. 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

3. The Rory story !!!
An infection , unnoticed , turn Unstoppable• 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

4. 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.

5. 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.

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

8. Why Sepsis again !!
Why new definitions !!
Why new scoring system !!

9. Why Sepsis is revisited again !!!
• It is still an economic burden on public health
▫ $ 20 billion of total US hospital cost 2011 (Torio et
al)
▫ Saudi Arabia ???
• Sepsis is the leading cause of death in non-
coronary care intensive care units, with a
mortality rate between 30-50%

10. 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

11. Hospitalization rates

12. Incidence and Cost

13. Why Sepsis again !!
Why new definitions !!
Why new scoring system !!

14. The old definitions
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15. 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.

16. 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
same
“We need to differentiate a straightforward
infection from one that can cause organ
dysfunction or death”

17. The overlap SIRS, infection, sepsis
and inflammation

18. Why Sepsis again !!
Why new definitions !!
Why new scoring system !!

19. 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

20. SIRS Criteria
• Two or more of:
▫ Temperature >38°C or <36°C
▫ Heart rate >90/min
▫ Respiratory rate >20/min or PaCO2 <32 mm Hg
(4.3 kPa)
▫ White blood cell count >12 000/mm3 or
<4000/mm3 or >10% immature bands
 Bone et al.Crit Care Med. 1992;20(6):864-874.

22. Sequential [Sepsis-Related] Organ
Failure Assessment Score

24. 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 ”

28. Introduction
• 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
care.

29. Introduction
• 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.

30. The Process of Developing New
Definitions
The co-chairs
Drs Deutschman & Singer)
• A task force of 19 critical
care, infectious disease,
surgical, and pulmonary
specialists in January
2014.
• The group engaged in
iterative discussions via
face-to-face meetings
between January 2014
and January 2015

31. 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
Acknowledgment).

32. Summary of Data Sets

33. Accrual of Encounters for Primary Cohort

34. What clinical criteria to study

35. 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 qSOFA,
▫ 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 sepsis.

36. New definitions
• Sepsis is defined as life-threatening organ
dysfunction caused by a dysregulated host
response to infection.
• NB:
▫ 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.

37. 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 dysfunction.

38. 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

39. 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.

41. 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.

42. Predictive Validity for Death

43. Area Under the Receiver Operating Characteristic Curve and
95%Confidence Intervals for In-Hospital Mortality of Candidate Criteria
(SIRS, SOFA, LODS, and qSOFA) Among Suspected Infection Encounters
in the UPMC Validation Cohort (N = 74 454)

44. 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
complex.
• For patients not in the ICU, the performance of
Quick SOFA score was similar to that of the
sequential organ failure assessment score.

45. Recommendation
• 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,.

46. A Need for Sepsis Definitions for the Public
and for Health Care Practitioners
• A life-threatening condition that arises when the
body’s response to infection injures its own
tissue.
• Finally, all these new definitions are
recommended for coding and research
purposes.

47. Terminology and international
classification of disease Coding

48. Recommended primary ICD codes
Sepsis Septic shock

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

50. Operationalization of clinical Criteria identifying
patients with sepsis & septic shock

51. 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
updates.

52. Conclusions
• 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.

53. 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 sepsis.

55. Finally
“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.