Septicemia

1. By: Dr PIRAH KORAI fcps -ii trainee cmc larkana

2. OUTLINES Terminology Etiology Pathology Clinical presentation Complications Investigations Management Prevention

3. 3

4. Infection Invasion of normally sterile host tissue by microorganisms 4

5. Bacteremia Presence of bacteria in blood Evidenced by positive blood culture 5

6. Septicemia Presence of microbes or toxins in blood 6

7. SIRS Two or more of the following conditions: Fever or hypothermia Tachypnea Tachycardia Leukocytosis or leukopenia or >10% bands Infectious / Noninfectious 7

8. Sepsis SIRS with proven or suspected microbial etiology 8

9. Severe sepsis Sepsis with signs of one or more organ dysfunction Cardiovascular: hypotension that responds to administration of IV fluids Renal Respiratory Hematologic Unexplained metabolic acidosis 9

10. Septic shock Sepsis with Hypotension, for at least 1 h, despite adequate fluid resuscitation Need for vasopressor 10

11. MODS Dysfunction of >1 organ Requiring intervention to maintain homeostasis 11

12. Septicemia can be a response to any class of microorganism ETIOLOGY Harrison’ s Internal Medicine 18 th edition 3

13. ETIOLOGY Blood cultures are positive : 20–40 % of Severe sepsis cases 40–70 % of septic shock cases Of cases with positive blood cultures, 40 % - gram-positive bacteria , 35 % t - gram-negative bacteria , 11 % - Polymicrobial 7 % - fungi <5% - classic pathogens Harrison’ s Internal Medicine 18 th edition 4

14. PATHOPHYSIOLOGY

15. 15

16. LBP Bacteria LPS Phagocyte CD 14 Toxin Recognition by the Host 11

17. LBP Bacteria LPS Phagocyte CD 14 LPS MD-2 TLR-4 TLR4 – transmembrane protein, transmits the LPS recognition signal to the interior of the cell, where signal transduction and gene transcription pathways promote the production and/or secretion of numerous molecules that mediate the inflammatory response LPS MD-2 Extracellular protein which binds the lipid A moiety of LPS Toxin Recognition by the Host Signaling complex Mandell Principles of Infectious Disease 12

18. Inflammatory Mediators TNF alpha Potent mediator of the subsequent inflammatory response Stimulates muscle breakdown and cachexia, mediates coagulation activation, enhances expression of adhesion molecules, prostaglandin E2 & PAF IL-1 Released in response to inflammation Endogenous pyrogen IL-6 Increasingly expressed during stress as in septic shock. Promote intravascular coagulation Other Interleukins, Cytokines and Chemokines  increased capillary permeability and blood flow, infiltration of neutrophils, and pain. Schwartz Principles of Surgery Mandell Principles of Infectious Disease 13

19. Inflammatory response to sepsis 19

20. 16

21. CLINICAL MANIFESTATION CLINICAL MANIFESTATION

22. Patients usually manifests symptoms and signs related to primary infection . Manifestations of Systemic Inflammatory Response Evidence of shock (-) fever : most common in neonates, elderly patients and in persons with uremia or alcoholism Harrison’ s Internal Medicine 18 th edition 17

23. Hyperventilation Encephalopathy Hypotension DIC,, ischemic necrosis of peripheral tissues (e.g., digits ) • Skin : hemorrhagic lesions, bullae, cellulitis • Gastrointestinal • Hypoxemia Harrison’ s Internal Medicine 18 th edition 18

24. MAJOR COMPLICATIONS l. Cardiopulmonary Complications Acute respiratory distress syndrome Hypotension Decrease Myocardial function II. Renal Complications Oliguira Azotemia Proteinuria Nonspecific casts 19

25. III. Coagulopathy • Thrombocytopenia • Platelet usually very low <50,000/ uL in pt with DIC IV. Neurological Complications • DDX: Guillain-Barre syndrome , metabolic disturbance , toxin activity MAJOR COMPLICATIONS Harrison’ s Internal Medicine 18 th edition 20

26. DIAGNOSIS OF SEPTICEMIA   

27.   C BC Renal function LFTs Blood Glucose Clotting screen, including D- dimer and fibrinogen testing Blood cultures Radiology - including CXR, abdominal u/s, CT Measures of serum lactate Arterial blood gases invasive investigations: lumbar puncture, bronchoscopy , laparoscopy, lymph node biopsy, etc.

28. Harrison’ s Internal Medicine 18 th edition Treatment: 27

29. Supportive care Resuscitation Intravenous rehydration Monitoring the patient Intravenous insulin Intravenous hydrocortisone

30. Specific therapy Intravenous antimicrobials Vasopressin Inotrope such as dobutamine if cardiac dysfunction occurs. Statins Activated protein C Surgery eg , wound debridement, abscess drainage

31. Other measures Nutritional supplementation Prophylactic heparinization Erythrocyte transfusion When Hb <7 g/dl Target level 9 g/dl 32

32. Other measures: cont… Bicarbonate Fresh frozen plasma and platelets Ventilator support Hemodialysis or hemofiltration 33

33. Ongoing trials IV Ig Endotoxin antagonist (eritoran) GM CSF 34