1. Sepsis Syndrome Bahram Hajikarim MD/MPH ZUMS Feb 2010

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

3. Mortality Percentage 0102030405060 UVA Hospital Johns Hopkins UVA newborn ICU UVA Enterococcus UIHC CNS UIHC Candida UIHC SICU

4. Stages of Sepsis Consensus Conference Definition Systemic Inflammatory Response Syndrome (SIRS) Two or more of the following: –Temperature of >38 o C or <36 0 C –Heart rate of >90 –Respiratory rate of >20 –WBC count >12 x 10 9 /L or <4 x 10 9 /L or 10% immature forms (bands) Sepsis 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) Septic Shock Hypotension (despite fluid resuscitation) plus hypoperfusion

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

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

9. Predisposing Underlying Diseases Heart disease-rheumatic or congenital Splenectomy Intraabdominal sepsis Septic abortion or pelvic infection Intravenous drug abuse Immunocompromised

10. Organisms Responsible for Septic Shock in Relation to Host Factors

12. Bacteremia in the Preantibiotic Era Streptococcus pneumoniae Group A streptococcus Staphylococcus aureus Haemophilus influenzae Neisseria mennigitidis Salmonella spp.

13. Emergence of Gram-Negative Organisms Antibiotic pressure on normal flora Use of invasive devices Immune suppression

14. Differential Diagnosis of Fever and Shock Purulent bacterial pericardial effusion Peritonitis Pneumonia with severe hypoxia Mediastinitis Anaphylaxsis Staphylococcal toxic shock syndrome Streptococcal toxic shock syndrome

15. Clinical Manifestations Fever, chills, hypotension Hypothermia, especially in the elderly Hyperventilation - respiratory alkalosis Diaphoresis, apprehension, change in mental status

16. History Community versus hospital-acquired Prior or current medications Recent manipulations or surgery Underlying diseases Travel history

17. Approach to Septic Patient Seek primary site of infection Direct therapy to primary site Repeated examination

18. Skin Furuncles, cellulitis, bullous lesions Intravenous sites, phlebitis Erythema multiforme Ecchymotic or purpuric lesions DIC, petechiae Ecthyma gangrenosum Purpura fulminans

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

20. Pulmonary Signs Tachypnea Hyperventilation, respiratory alkalosis ARDS, respiratory failure Ventilation-perfusion mismatch Widened alveolar-arterial oxygen gradient Reduced lung compliance

21. Hematologic Findings Neutrophilic leukocytosis Leukemoid reaction Neutropenia Thrombocytopenia Toxic granulations DIC

22. Renal and Gastrointestinal Signs Acute tubular necrosis, oliguria, anuria Upper GI bleeding Cholestatic jaundice Increased transaminase levels Hypoglycemia

23. Acute Physiology and Chronic Health Evaluation APACHE II TempArterial pH MAPSerum Na; Serum Cr Heart rateHematocrit Resp. rateWBC OxygenationGlasgow Coma Score Acute physiology score + Age + Chronic health points

24. Laboratory Studies Blood cultures Infected secretions/body fluids Stool for WBC, C. difficile Aspirate advancing edge of cellulitis Skin biopsy/scraping Buffy coat

25. Therapy of Septic Shock Correct pathologic condition Optimize intravascular volume Administer empiric antimicrobial therapy Administer vasoactive drugs

26. Failure of Fluid Replacement and Vasopressors acidosis - pH<7.3 hypocalcemia adrenal insufficiency hypoglycemia

27. Empiric Antimicrobial Regimens for Sepsis Syndrome Community-acquired non-neutropenic –Urinary tract: 3rd generation cepholosporin, piperacillin, quinolone + AG –Non-urinary tract: 3rd generation cepholosporin + metronidazole,  -lactam/  - lactamase inhibitor + AG

28. Hospital-acquired –Nonneutropenic: 3rd generation cephalosporin + metronidazole,  -lactam /  -lactamase inhibitor, menopenem all + AG –Neutropenic: Timentin + AG, meropenem + AG; ceftazidime + metronidazole + AG

29. Septic Shock Outcomes for Patients on Hospital Wards versus ICU’s Ward patients:Delays in ICU transfer (67 mins.) IV fluid boluses (27 vs 15 mins.) Inotropic agents (310 vs 22.5 mins) Mortality:Wards (70%) vs ICUs (39%) Apache II scores (18.5 vs 24) Candidemia JS Lunberg, Crit. Care Med. 26:1020; 1998

30. Immunotherapies for Septic Shock Corticosteroids Antiendotoxin monoclonal antibodies E-5, HA-1A Anti-TNF antibodies IL-1 receptor antagonists

31. Other Treatment Modalities Granulocyte transfusions Recombinant colony-stimulating factors Diuretics Pentoxifylline, ibuprofen, naloxone Oral nonabsorbable antimicrobial agents