1. Current concept of pathophysiology of sepsis
Manutham Manavathongchai MD

2. ACCP/SCCM Consensus definitions
Systemic inflammatory response syndrome ( SIRS)
Tachycardia, HR >2 SD, <1yr bradycardia
Mean RR >2 SD
WBC elevate or depressed for age
Core temp >38.5 °C or <36 °C
one of two have to be abn Temp or WBC

3. ACCP/SCCM Consensus definitions
Infection
Inflammatory response to microorganisms, or
Invasion of normally sterile tissues

4. ACCP/SCCM Consensus definitions
Sepsis
Infection plus
SIRS criteria

5. ACCP/SCCM Consensus definitions
Severe Sepsis
Sepsis plus
Cardiovascular dysfunction or
Acute respiratory distress syndrome (ARDS) or
Other 2 organs dysfunction

6. Organ dysfunction Cardiovacular pulmonologic Neurologic Hematologic
Renal
Hepatic

7. ACCP/SCCM Consensus definitions
Septic shock
Sepsis plus
Hypotension despite fluid resuscitation or
Need vasoactive drugs or
2 organs dysfunction

8. Sepsis
This conceptual framework shows the interrelationships between infection, non-infectious disorders, SIRS, sepsis, and severe sepsis. Components of the process not discussed on the following slides include:
Infection: a microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms
Bacteremia: the presence of viable bacteria in the blood stream
Septic shock: sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status
Multiple organ dysfunction syndrome (MODS): presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention
Inflammation and hemostasis are tightly linked. Therefore, although not shown on this slide, sepsis and severe sepsis lie on a background of disturbed hemostasis.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000;28:S81-2.
Adapted from: Bone RC et al. Chest. 1992;101:
Opal SM et al. Crit Care Med. 2000;28:S81-2.

9. ACCP/SCCM Consensus definitions
Multiple Organ Dysfunction Syndrome (MODS)
Altered organ function in an acutely ill patient
Homeostasis cannot be maintained without intervention

10. Early sepsis
Innate system (non specific)
Adaptive system (specific)

11. Innate system (non specific)
Cell adhesion molecules
Procoagulants and anticoagulants
Nitric oxide synthase

12. Russel JA. N Engl J Med 2006;355:1699-713

14. Russel JA. N Engl J Med 2006;355:1699-713

15. Ann Emerg Med. 2006;48:28-54

16. Depletion of platelets and coagulation factors
SYSTEMIC ACTIVATION OF COAGULATION
Intravascular
deposition of fibrin
Depletion of platelets
and coagulation factors
Bleeding
Thrombosis of small
and midsize vessels
Organ failure
DEATH

17. Septic shock Role of NO Infection induce NOS expression
High level Help eradicate infection but Also cause vasodilation/ Massive hypotension
Samjot S et al Chest 2005;128:1706

18. Activated protein c in Pediatric septic shock
P<0.01, n=30 60 50 40
Activated protein C activity 30 20 10
Survivors
Non-Survivors
Samransamruajkit et al ATS 2005

19. Adaptive system (specific)
Cell-mediated response (T-cells)
Humoral response (B-cells)

21. Organ dysfunction Circulatory dysfunction: redistribution of bl flow
: vascular resistance
: myocardial contraction
Acute lung injury : microvascular permeability
Liver, kidney , CNS dysfunction

22. Septic shock stage/Course
Early resuscitation
Aggressive Rx
Paliative Rx
“Early
Warm Shock”
“Reversible
Phase”
“Irreversible
Phase”

23. Septic shock General principle summary
Early
Recognition
Immediate
Resuscitation
**Prevention
Stabilization
Prevention
Prophylactic
Abx P Iatrogenic Vaccine
Early
Recognition Warm Shock Reversible signs of hypo
Perfusion
Wide PP UO
Immediate
Resuscitation 1 st HR
Resuscitation ABC Volume Inotrope Steroids
Stabilization Hemodynamic
support Appropriate Inotrope use
Close monitoring Nutrition