1. Sepsis Syndromes

2. Sepsis and Septic Shock 13th leading cause of death in U.S.13th leading cause of death in U.S. 500,000 episodes each year500,000 episodes each year 35% mortality35% mortality 30-50% culture-positive blood30-50% culture-positive blood

3. Consensus Conference Definition Consensus Conference Definition Systemic Inflammatory Response Syndrome (SIRS) Two or more of the following:Systemic Inflammatory Response Syndrome (SIRS) Two or more of the following: –Temperature of >38 o C or 38 o C or <36 0 C –Heart rate of >90 –Respiratory rate of >20 –WBC count >12 x 10 9 /L or 12 x 10 9 /L or <4 x 10 9 /L or 10% immature forms (bands) Sepsis SIRS plus a culture-documented infectionSepsis SIRS plus a culture-documented infection Severe Sepsis Sepsis plus organ dysfunction, hypotension, or hypoperfusion (including but not limited to lactic acidosis, oliguria, or acute mental status changes)Severe Sepsis Sepsis plus organ dysfunction, hypotension, or hypoperfusion (including but not limited to lactic acidosis, oliguria, or acute mental status changes) Septic Shock Hypotension (despite fluid resuscitation) plus hypoperfusionSeptic Shock Hypotension (despite fluid resuscitation) plus hypoperfusion

4. Multiple Organ Dysfunction Syndrome Dysfunction of 2 or more systemsDysfunction of 2 or more systems Four or more systems - mortality near to 100 percentFour or more systems - mortality near to 100 percent

7. Factors Associated with Highest Mortality Respiratory > abdominal > urinaryRespiratory > abdominal > urinary Nosocomial infectionNosocomial infection Hypotension, anuriaHypotension, anuria Isolation of enterococci or fungiIsolation of enterococci or fungi Gram-negative bacteremia, polymicrobialGram-negative bacteremia, polymicrobial Body temperature lower than 38°CBody temperature lower than 38°C Age greater than 40Age greater than 40 Underlying illness: cirrhosis or malignancyUnderlying illness: cirrhosis or malignancy

8. Clinical Manifestations Fever, chills, hypotensionFever, chills, hypotension Hypothermia, especially in the elderlyHypothermia, especially in the elderly Hyperventilation - respiratory alkalosisHyperventilation - respiratory alkalosis Diaphoresis, apprehension, change in mental statusDiaphoresis, apprehension, change in mental status

9. Cardiovascular Signs “Warm shock” -  CO,  SVR“Warm shock” -  CO,  SVR “Cold shock” -  CO,  SVR“Cold shock” -  CO,  SVR Anaerobic metabolism - lactic acidemiaAnaerobic metabolism - lactic acidemia Myocardial depressant factor - ??Myocardial depressant factor - ??

10. Pulmonary Signs TachypneaTachypnea Hyperventilation, respiratory alkalosisHyperventilation, respiratory alkalosis ARDS, respiratory failureARDS, respiratory failure Ventilation-perfusion mismatchVentilation-perfusion mismatch Widened alveolar-arterial oxygen gradientWidened alveolar-arterial oxygen gradient Reduced lung complianceReduced lung compliance

11. Hematologic Findings Neutrophilic leukocytosisNeutrophilic leukocytosis Leukemoid reactionLeukemoid reaction NeutropeniaNeutropenia ThrombocytopeniaThrombocytopenia Toxic granulationsToxic granulations DICDIC

12. Renal and Gastrointestinal Signs Acute tubular necrosis, oliguria, anuriaAcute tubular necrosis, oliguria, anuria Upper GI bleedingUpper GI bleeding Cholestatic jaundiceCholestatic jaundice Increased transaminase levelsIncreased transaminase levels HypoglycemiaHypoglycemia

13. Therapy of Septic Shock Correct pathologic conditionCorrect pathologic condition Optimize intravascular volumeOptimize intravascular volume Administer empiric antimicrobial therapyAdminister empiric antimicrobial therapy Administer vasoactive drugsAdminister vasoactive drugs Support failing systems.Support failing systems.

14. Latest advances Tight glucose control.Tight glucose control. Early goal directed resuscitation.Early goal directed resuscitation. Corticosteroids.Corticosteroids. Activated protein C (?)Activated protein C (?)