This document discusses the potential need for an updated definition of sepsis (Sepsis-4) by reviewing the current Sepsis-3 definition. It summarizes various studies and opinions that have questioned aspects of Sepsis-3, such as the validation of the quick Sequential Organ Failure Assessment (qSOFA) score and the lack of evidence that it predicts outcomes better than other scoring tools. The document concludes that Sepsis-3 definitions may be falling out of practice favor and that developing Sepsis-4 will require significant work from medical societies to create practical global definitions of sepsis that incorporate perspectives from low- and middle-income countries.

1. Sepsis and Septic Shock;
Are We Ready for “Sepsis-4”?
Akram M Fayed, MD, ABIM
Professor, Department of Critical Care Medicine,
Faculty of Medicine
University of Alexandria, Egypt
1/18/2017
1

2. 1/18/2017
2
Objectives
 Review of Sepsis- 3 “Singer et. al”
 Overview of different authors’ Opinions
(Editorials)
 Highlights on Singer’s Editorial in November
2016
 Conclusion

3. 1/18/2017 3

4. 1/18/2017
4

5. 1/18/2017 5

6. 1/18/2017
6

7. 1/18/2017
7

8. 1/18/2017 8

9. 1/18/2017
9

10. 1/18/2017
10

11. 1/18/2017 11
AJRCCM Articles in Press. Published on 20-September-2016

12. 1/18/2017 12
Methods:
 All admitted patients first meeting criteria for suspicion of
infection in the ED or hospital wards from November 2008 until
January 2016 were included
 The qSOFA, (SIRS), Modified Early Warning Score (MEWS),
and the National Early Warning Score (NEWS) were compared
for predicting death and ICU transfer
 30,677 patients

13. 1/18/2017 13

14. 1/18/2017 14

15. 1/18/2017 15

16. 1/18/2017 16

17. 1/18/2017 17

18. 1/18/2017 18

19. 1/18/2017 19

20. 1/18/2017 20

21. 1/18/2017
21
Conclusions
 Churpek et al. 2016 is the first study to attempt
validation of qSOFA
 qSOFA and SIRS have similar overall performance
in predicting the combined outcome of death or ICU
transfer
 qSOFA has a higher specificity, but this comes as a
tradeoff for lower sensitivity

22. 1/18/2017
22
Conclusions
 qSOFA is <40% sensitive for detecting a patient who will
die or need ICU transfer in 12 hours
 qSOFA is consistently out-performed by the NEWS
score, a more sophisticated bedside risk-stratification
tool
 This study doesn’t support the Sepsis-3 definition
 Further evidence is needed before considering the
widespread adoption of qSOFA and Sepsis-3
 The British approach using the NEWS score appears
superior

23. 1/18/2017 23

24. 1/18/2017 24
Published online: 3 November 2016

25. 1/18/2017 25

26. 1/18/2017 26

27. 1/18/2017
27
Recommendations
 Compare the old versus the new definitions using RCTs
and epidemiological studies of sepsis and septic shock.
The evaluation could demonstrate whether there is a need
for the old definition of sepsis and whether SBP or MAP
should be used
 Evaluate the role of single or multiple biomarkers or
genetic, epigenetic, inflammatory or anti-inflammatory
factors to enhance the definition and/or provide important
surrogate end-points to guide management decisions

28. 1/18/2017
28
Conclusions
 Refine the SOFA score to define worsening organ
dysfunction taking into account change from preexisting
organ dysfunction secondary to sepsis
Incorporate clinical parameters to define organ dysfunction
for LMICs and thus expand the utility of the score globally
 Determine diagnostic methodologies to differentiate
infected from non-infected patients

29. Published online: 3 November 2016

30. 1/18/2017
30

31. 1/18/2017 31

32. 1/18/2017 32

33. 1/18/2017 33

34. 1/18/2017 34

35. 1/18/2017 35

36. 1/18/2017 36

37. Conclusions
 Sepsis-3 definitions are falling out of favor in terms of
real practice Critical Care Medicine
 Older versions of sepsis definitions might be simpler and
self- explanatory compared to Sepsis- 3 definitions
keeping the continuum of the sepsis spectrum
 Sepsis- 4 is mostly on its way but it requires much work
from the societies (may be with incorporation of LMICs
representatives) to translate the definitions of sepsis into
practical ones that could be applied all over the globe
1/18/2017 37

38. 1/18/2017 38
Thank You