1. Patho-Physiology and ICU Management of Septic Shock Dr.T.R.ChandraShekar Director critical care, K.R.Hospital, Bengaluru

6. Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Shock Bacteria Fungus Parasites Virus SIRS INFECTION PANCREATITIS BURNS TRAUMA OTHER SEPSIS SEVERE SEPSIS SEPTIC SHOCK

7. Definitions SIRS Sepsis Severe Sepsis Septic Shock Infection DO WE REQUIRE TO CHANGE THE DEFINITION? MODS

9. Arterial hypotension Tachycardia Altered skin perfusion Decreased U.O Hyperlactatemia – Altered WBC count Increased CRP, PCT concentrations Rigor– fever Tachypnea Positive fluid balance – edema General signs & symptoms General inflammatory reaction Hemodynamic alterations Signs of organ dysfunction Hypoxemia Coagulation abnormalities Altered mental status Expanded signs of SIRS

11. Pathogenesis of shock Microcirculatory Mitochondrial dysfunction Cardiac dysfunction, Microemboli, Microvasular injury, increased Nitric oxide- Vasoplegia Cytokines & inflammatory mediator cascade Interaction with human cells- macrophages Monocytes, Neutrophils, Endothelial cells Infectious trigger

12. Toll receptors

14. Toll receptors Pathogen-associated molecular patterns (PAMPs) Host factors Immunosuppressed Extremes of age Malnutrition Alcohol, Drug Abuse Malignancy HIV/AIDS Chronic Health Issues – Diabetes, Liver Failure, Heart Disease, Corticosteroids, Chemotherapy Multiple invasive procedures or invasive lines

15. PRO INFLAMMATORY Promotes-Inflammation Coagulation Inhibits-Anti-coagulants, Fibrinilysis. IL-1; TNF IL-6; IL-8 ANTI-INFLAMATORY Inhibits- Inflammation Coagulation Immunosupression Anti-Inflammatories: IL-1ra; IL-4; IL-10 S MONOCYTE DERIVED CYTOKINES INFECTION/MICROBIAL TRIGGER SIRS CARS Systemic Inflammatory Response Syndrome Compensatory Anti- Inflammatory Response Syndrome

16. Crit Care Med 2000, 28(4):N105-N113 with modification Infection Immune Response Sepsis Uncontrolled Pro-inflammatory Mechanisms Dysregulated anti-inflammatory Mechanisms SIRS MODS/MOF

17. Why some patients do well others die ? Death Infection Toxins Host defenses Overwhelming infection Death Sepsis Excessive Survival MODS Adequate Coordinated Infection control Survival Why? Why? Unregulated Host factors Delayed therapy Genetic predisposition HLA class III genes TNF a gene promoter Inadequate

19. Coagulation in Sepsis Bernard GR, et al. New Engl J Med, 2001;344:699-709. Coagulation Inflammation Fibrinolysis Micro-emboli Inflammatory Response Inflammatory Response to Infection Thrombotic Response to Infection Fibrinolytic Response to Infection Endothelium TAFI PAI-1 Suppressed fibrinolysis Neutrophil Monocyte IL-6 IL-1 TNF  Bacterial, viral, fungal or parasitic infection/endotoxin Bacterial, viral, fungal or parasitic infection/endotoxin IL-6 Tissue Factor Tissue Factor COAGULATION CASCADE Factor Va Factor VIIIa THROMBIN Fibrin Fibrin clot

20. CARDIOVASCULAR FAILURE Vasodilatation (nitric oxide release) Hypovolemia Myocardial dysfunction Cell metabolism alteration Decrease vascular resistance Tachycardia , Hypotension, Hypoperfusion

21. Final pathway in sepsis Sepsis is a disease of the microcirculation Vasoplegia , Cardiac dysfunction, Capillary leak Hypovolemia,Maldistribution Microemboli Microcirculatory Mitochondrial Dysfunction syndrome (MMDS) Cell death-Organ injury –MODS- Death

31. Even with the ‘best’ parameters it is not always easy to make the right decision.………

32. EGDT Suspected infection Blood cultures Obtain two or more BCs One or more BCs should be percutaneous One BC from each vascular access device in place more than equal to 48 hrs Culture other sites as clinically indicated. Other diagnostic/imaging as indicated Appropriate Empirical Antibiotics with in 1 hr/ source control Host factors/ local antibiogram/ suspected site Combination antibiotics/ right dose SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l

33. Antibiotics Always look at you local organisms and resistance patterns Early antibiotic therapy Right dose

35. Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control CVP MAP Goal achieved SCVO2 < 8 Fluids NS, RL/ Colloid 8-12 >60-90mmHg < 60-90 Vasopressors Noradrenaline/dopamine <70% < 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70% Decrease Oxygen consumption

37. Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control CVP MAP Goal achieved SCVO2 < 8 Fluids NS, RL/ Colloid 8-12 >60-90mmHg < 60-90 Vasopressors Noradrenaline/dopamine <70% < 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70% Decrease Oxygen consumption

39. Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control CVP MAP Goal achieved SCVO2 < 8 Fluids NS, RL/ Colloid 8-12 >60-90mmHg < 60-90 Vasopressors Noradrenaline/dopamine <70% < 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70% Decrease Oxygen consumption

41. EGDT

45. Thank you