1. Systemic Inflammatory Response Syndrome (SIRS) Lu Ning, MD Assistant Professor of Surgery

8. Relationship Between Sepsis and SIRS TRAUMA BURNS PANCREATITIS SEPSIS SIRS INFECTION SEPSIS BACTEREMIA

9. SIRS Continuum Source: Bone et al. Chest 1992;101:1644 SIRS OTHER INFECTION PANCREATITIS BURNS TRAUMA SEPSIS SEVERE SEPSIS SEPTIC SHOCK

14. Mortality rate in SIRS Rangel - Frausto, et al. JAMA 273:117-123, 1995.

15. Mortality Increases in Septic Shock Patients Mortality Incidence Source: Balk, R.A. Crit Care Clin 2000;337:52 Approximately 200,000 patients including 70,000 Medicare patients have septic shock annually Septic Shock 53-63% 20-53% Severe Sepsis 300,000 7-17% Sepsis 400,000

16. The Response to Pathogens “Cross-Talk” NEJM 2003;348:138-150.

17. Inflammatory Response to Sepsis NEJM 2006;355:1699-1713.

18. Procoagulant Response in Sepsis NEJM 2006;355:1699-1713.

19. Pathogenesis of sepsis and septic shock Angus DC, et al . Crit Care Med 2001, 29:1303-1310.

20. Pathogenesis of Severe Sepsis Infection Microbial Products (exotoxin/endotoxin) Cellular Responses Oxidases Platelet Activation Kinins Complement Coagulopathy/DIC Vascular/Organ System Injury Multi-Organ Failure Death Endothelial damage Endothelial damage Coagulation Activation Cytokines TNF, IL-1, IL-6

34. Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock Dellinger RP, et al. Crit Care Med 2004; 32:858-873.

40. Early Goal-Directed Therapy CVP : central venous pressure MAP : mean arterial pressure ScvO 2 : central venous oxygen saturation NEJM 2001;345:1368-77 .

41. Early Goal-Directed Therapy Results 49.2% 33.3% 0 10 20 30 40 50 60 Standard Therapy n=133 EGDT n=130 P = 0.01* *Key difference was in sudden CV collapse, not MODS 28-day Mortality NEJM 2001;345:1368-77.

46. Multiple Organ Dysfunction Syndrome (MODS)

51. Mechanism

52. Inflammatory mediators priming SIRS leading to MODS Vascular permeability ↑ ＋ PMN chemotaxis Mono / Macrophage PMN elastase PLA2 oxygen free radicals TNF IL － 8 IL － 1 IL － 6 Liver ： acute phase Remote organ injury Tissue injury Endothelium Injury factors PMN PAF Adhensive molecules DIC

53. Common Manifestations of MODS DIC Coagulation CNS failure Brain Acute hepatic failure Liver Stress ulcer/enteroparalysis Gastro-intestine ARF Kidney ALI /ARDS Lung Shock Peripheral circulation Acute heart failure Heart Symptoms Organ

54. Diagnosis of Criteria

55. Organ/ system dysfunction and failure

56. GLASGOW SCORE

58. Treatments of MODS