This document discusses sepsis, septicemia, and multiple organ dysfunction syndrome (MODS). It defines related terms like bacteremia, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. It discusses the magnitude of the problem globally and in India. It covers the pathophysiology and most common sources of infection. It also summarizes the Surviving Sepsis Campaign guidelines for management of sepsis and septic shock. Finally, it provides an overview of recent advances and controversies in the field and lists various biomarkers that can be used for diagnosis, prognosis, and stratification of sepsis severity.

1. SEPTICEMIA AND MODS

2. overview
A. Definitions
B. Magnitude of the problem
C. Sepsis – A complex entity
D. Source of infection ?
E. Pathophysiological basis of abnormalies
F. Surviving Sepsis Campaign – Addressing the issue
globally
 History of SSC
 Management Guidelines
 The “bundle” approach
G. Recent advances
H. Biomarkers

3. definitions
Bacteremia - Presence of bacteria in blood, as evidenced
by positive blood cultures.
Septicemia - Presence of microbes or their toxins in
blood.

4. definitions
 SIRS - A clinical response
arising from a nonspecific
insult manifested by
2 of the following:
 Temperature
38°C or 36°C
 HR 90 beats/min
 Respirations 20/min
 WBC count 12,000/mL or
4,000/mL or >10%
immature neutrophils

5. definitions
 Sepsis:
 Known or suspected
infection
 SIRS criteria

6. definitions
 Severe Sepsis =
Sepsis with signs of acute
organ dysfunction in any of
the following systems:
 Cardiovascular (septic
shock)
 Renal
 Respiratory
 Hepatic
 Hemostasis
 CNS
 Unexplained metabolic
acidosis

7. definitions
Septic shock- Sepsis, with
hypotension (SBP <90 mmHg systolic, or
40 mmHg less than patient's normal
blood pressure) for at least 1 h despite adequate
fluid resuscitation,
or
Need for vasopressors to maintain systolic
blood pressure 90 mmHg or mean arterial
pressure 70 mmHg

8. definitions
MODS - Dysfunction of more than one organ, requiring
intervention to maintain homeostasis.

9. Sepsis – A complex entity

10. Magnitude of the problem

11. Magnitude of the problem - India

12. SOURCE OF INFECTION
Organisms Most common source
Gram negative pathogen Pneumonia
Coagulase –ve Staph. Vascular catheters
Staph. aureus Pneumonia
Enterococci Pneumonia
Streptococci Unknown
Anaerobic organisms Pneumonia
Candida spp. Vascular catheters

13. pathophysiology

14. Surviving sepsis campaign - An
international consortium
 First set of guidelines – 2004
 Revised – 2008
 Current – 2012

15. Ssc guidelines – Initial resuscitation &
infection issues

16. Ssc guidelines – Initial resuscitation &
infection issues

17. Ssc guidelines – Initial resuscitation &
infection issues

18. Ssc guidelines – Initial resuscitation &
infection issues

19. Ssc guidelines – Hemodynamic support
& adjunctive therapy

20. Ssc guidelines – Hemodynamic support
& adjunctive therapy

21. Ssc guidelines – Hemodynamic support
& adjunctive therapy

22. Ssc guidelines – Hemodynamic support
& adjunctive therapy

23. Ssc guidelines – Other supportive therapy

24. Ssc guidelines – Other supportive therapy

25. Ssc - The “bundle” approach

26. Ssc guidelines – Other supportive therapy

27. Surviving sepsis campaign –
Guidelines

28. Surviving sepsis campaign –
Guidelines

29. Surviving sepsis campaign –
Guidelines

30. Ssc guidelines – Other supportive therapy

31. Recent advances & controversies

32. Recent advances & controversies

33. Recent advances & controversies

34. • Sepsis leads to
– Inflammation
– Coagulation
– Tissue damage and repair
• The sicker you are, the greater the changes
• We can identify biomarkers for these processes
• We can measure these biomarkers
• We can stratify severity based on biomarker levels
• We can prognosticate based on biomarker levels
biomarkers

35. • Acute phase proteins
– CRP
– Procalcitonin
– Pentraxin 3 (PTX3)
– Lipopolysaccharide binding protein (LBP)
• Cytokines & chemokines
– IL-1RA, IL-1b,IL-2, IL-6, MCP-1
– TNF-a, TNFR1/2
– HMGBP1
• Cell surface markers
– Soluble CD14 (presepsin)
– Neutrophil CD64 index (CD64in)
– mHLA-DR (monocyte HLA-DR levels)
– CD-163
• Receptor markers
– VEGF
– Soluble VEGF-receptor 1 (sFLT)
– Soluble urokinase plasminogen activator (suPAR)
– sTREM-1
– RAGE (soluble receptor for advanced glycation
end products)
• Coagulation
– Activated partial thromboplastin time
(aPTT) waveform analysis
– Protein C receptor
– Thrombomodulin
• Endothelial damage
– Heparin binding protein
– E-selectin
– Neopterin
– ICAM-1, VCAM-1
– Angiopoietin-1 and -2
– Syndecan-1 and -2
• Vasodilation
– Copeptin (AVP precursor)
• Cell damage
– MicroRNA
– Microparticles
• Cell repair
– Procollagen III amino propeptide
Biomarkers - Examples

36. • Bacterial infections
– > ubiqitous CALC-1 gene expression
– > release of PCT from all parenchymal tissues
– Procalcitonin (PCT) increases after 2-3 hours after
induction e.g. by endotoxin
– Falls with successful treatment
Biomarkers - Procalcitonin

37. • Pentraxins are liquid-phase PAMP receptors
• “Short” pentraxins include CRP as is serum amyloid
P component (SAP)
• Pentraxin-3 involved in:
– complement activation
– pathogen opsonisation
– self versus modified-self versus non-self discrimination
Biomarkers - Pentraxin

38. Thank you