Sepsis Syndrome Cynthia L. Gibert, M.D. Washington VA Medical Center Georgetown University Medical Center
Sepsis and Septic Shock <ul><li>13th leading cause of death in U.S. </li></ul><ul><li>500,000 episodes each year </li></ul...
Mortality Percentage 0 10 20 30 40 50 60 UVA Hospital Johns Hopkins UVA newborn ICU UVA Enterococcus UIHC CNS UIHC Candida...
Stages of Sepsis Consensus Conference Definition <ul><li>Systemic Inflammatory Response Syndrome (SIRS) Two or more of the...
Multiple Organ Dysfunction Syndrome <ul><li>Dysfunction of 2 or more systems </li></ul><ul><li>Four or more systems - mort...
 
 
Factors Associated with Highest Mortality <ul><li>Respiratory > abdominal > urinary </li></ul><ul><li>Nosocomial infection...
Predisposing Underlying Diseases <ul><li>Heart disease-rheumatic or congenital </li></ul><ul><li>Splenectomy </li></ul><ul...
Organisms Responsible for Septic Shock in Relation to Host Factors
 
Bacteremia   in the Preantibiotic Era <ul><li>Streptococcus   pneumoniae </li></ul><ul><li>Group A streptococcus </li></ul...
Emergence of  Gram-Negative Organisms <ul><li>Antibiotic pressure on normal flora </li></ul><ul><li>Use of invasive device...
Differential Diagnosis  of Fever and Shock <ul><li>Purulent bacterial pericardial effusion </li></ul><ul><li>Peritonitis <...
Clinical Manifestations <ul><li>Fever, chills, hypotension </li></ul><ul><li>Hypothermia, especially in the elderly </li><...
History <ul><li>Community versus hospital-acquired </li></ul><ul><li>Prior or current medications </li></ul><ul><li>Recent...
Approach to Septic Patient <ul><li>Seek primary site of infection </li></ul><ul><li>Direct therapy to primary site </li></...
Skin <ul><li>Furuncles, cellulitis, bullous lesions </li></ul><ul><li>Intravenous sites, phlebitis </li></ul><ul><li>Eryth...
Cardiovascular Signs <ul><li>“ Warm shock” -    CO,    SVR </li></ul><ul><li>“ Cold shock” -    CO,    SVR </li></ul><...
Pulmonary Signs <ul><li>Tachypnea </li></ul><ul><li>Hyperventilation, respiratory alkalosis </li></ul><ul><li>ARDS, respir...
Hematologic Findings <ul><li>Neutrophilic leukocytosis </li></ul><ul><li>Leukemoid reaction </li></ul><ul><li>Neutropenia ...
Renal and  Gastrointestinal Signs <ul><li>Acute tubular necrosis, oliguria, anuria </li></ul><ul><li>Upper GI bleeding </l...
Acute Physiology and  Chronic Health Evaluation <ul><li>APACHE II </li></ul><ul><li>Temp Arterial pH </li></ul><ul><li>MAP...
Laboratory Studies <ul><li>Blood cultures </li></ul><ul><li>Infected secretions/body fluids </li></ul><ul><li>Stool for WB...
Therapy of Septic Shock <ul><li>Correct pathologic condition </li></ul><ul><li>Optimize intravascular volume </li></ul><ul...
Failure of Fluid Replacement and Vasopressors <ul><li>acidosis - pH<7.3 </li></ul><ul><li>hypocalcemia </li></ul><ul><li>a...
Empiric Antimicrobial Regimens for Sepsis Syndrome <ul><li>Community-acquired non-neutropenic </li></ul><ul><ul><li>Urinar...
<ul><li>Hospital-acquired </li></ul><ul><ul><li>Nonneutropenic:  3rd generation cephalosporin + metronidazole,   -lactam ...
Septic Shock Outcomes for Patients on  Hospital Wards versus ICU’s <ul><li>Ward patients: Delays in ICU transfer (67 mins....
Immunotherapies for  Septic Shock <ul><li>Corticosteroids </li></ul><ul><li>Antiendotoxin monoclonal antibodies E-5, HA-1A...
Other Treatment Modalities <ul><li>Granulocyte transfusions </li></ul><ul><li>Recombinant colony-stimulating factors </li>...
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Sepsis

  1. 1. Sepsis Syndrome Cynthia L. Gibert, M.D. Washington VA Medical Center Georgetown University Medical Center
  2. 2. Sepsis and Septic Shock <ul><li>13th leading cause of death in U.S. </li></ul><ul><li>500,000 episodes each year </li></ul><ul><li>35% mortality </li></ul><ul><li>30-50% culture-positive blood </li></ul>
  3. 3. Mortality Percentage 0 10 20 30 40 50 60 UVA Hospital Johns Hopkins UVA newborn ICU UVA Enterococcus UIHC CNS UIHC Candida UIHC SICU
  4. 4. Stages of Sepsis Consensus Conference Definition <ul><li>Systemic Inflammatory Response Syndrome (SIRS) Two or more of the following: </li></ul><ul><ul><li>Temperature of >38 o C or <36 0 C </li></ul></ul><ul><ul><li>Heart rate of >90 </li></ul></ul><ul><ul><li>Respiratory rate of >20 </li></ul></ul><ul><ul><li>WBC count >12 x 10 9 /L or <4 x 10 9 /L or 10% immature forms (bands) </li></ul></ul><ul><li>Sepsis SIRS plus a culture-documented infection </li></ul><ul><li>Severe Sepsis Sepsis plus organ dysfunction, hypotension, or hypoperfusion (including but not limited to lactic acidosis, oliguria, or acute mental status changes) </li></ul><ul><li>Septic Shock Hypotension (despite fluid resuscitation) plus hypoperfusion </li></ul>
  5. 5. Multiple Organ Dysfunction Syndrome <ul><li>Dysfunction of 2 or more systems </li></ul><ul><li>Four or more systems - mortality near to 100 percent </li></ul>
  6. 8. Factors Associated with Highest Mortality <ul><li>Respiratory > abdominal > urinary </li></ul><ul><li>Nosocomial infection </li></ul><ul><li>Hypotension, anuria </li></ul><ul><li>Isolation of enterococci or fungi </li></ul><ul><li>Gram-negative bacteremia, polymicrobial </li></ul><ul><li>Body temperature lower than 38°C </li></ul><ul><li>Age greater than 40 </li></ul><ul><li>Underlying illness: cirrhosis or malignancy </li></ul>
  7. 9. Predisposing Underlying Diseases <ul><li>Heart disease-rheumatic or congenital </li></ul><ul><li>Splenectomy </li></ul><ul><li>Intraabdominal sepsis </li></ul><ul><li>Septic abortion or pelvic infection </li></ul><ul><li>Intravenous drug abuse </li></ul><ul><li>Immunocompromised </li></ul>
  8. 10. Organisms Responsible for Septic Shock in Relation to Host Factors
  9. 12. Bacteremia in the Preantibiotic Era <ul><li>Streptococcus pneumoniae </li></ul><ul><li>Group A streptococcus </li></ul><ul><li>Staphylococcus aureus </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Neisseria mennigitidis </li></ul><ul><li>Salmonella spp. </li></ul>
  10. 13. Emergence of Gram-Negative Organisms <ul><li>Antibiotic pressure on normal flora </li></ul><ul><li>Use of invasive devices </li></ul><ul><li>Immune suppression </li></ul>
  11. 14. Differential Diagnosis of Fever and Shock <ul><li>Purulent bacterial pericardial effusion </li></ul><ul><li>Peritonitis </li></ul><ul><li>Pneumonia with severe hypoxia </li></ul><ul><li>Mediastinitis </li></ul><ul><li>Anaphylaxsis </li></ul><ul><li>Staphylococcal toxic shock syndrome </li></ul><ul><li>Streptococcal toxic shock syndrome </li></ul>
  12. 15. Clinical Manifestations <ul><li>Fever, chills, hypotension </li></ul><ul><li>Hypothermia, especially in the elderly </li></ul><ul><li>Hyperventilation - respiratory alkalosis </li></ul><ul><li>Diaphoresis, apprehension, change in mental status </li></ul>
  13. 16. History <ul><li>Community versus hospital-acquired </li></ul><ul><li>Prior or current medications </li></ul><ul><li>Recent manipulations or surgery </li></ul><ul><li>Underlying diseases </li></ul><ul><li>Travel history </li></ul>
  14. 17. Approach to Septic Patient <ul><li>Seek primary site of infection </li></ul><ul><li>Direct therapy to primary site </li></ul><ul><li>Repeated examination </li></ul>
  15. 18. Skin <ul><li>Furuncles, cellulitis, bullous lesions </li></ul><ul><li>Intravenous sites, phlebitis </li></ul><ul><li>Erythema multiforme </li></ul><ul><li>Ecchymotic or purpuric lesions </li></ul><ul><li>DIC, petechiae </li></ul><ul><li>Ecthyma gangrenosum </li></ul><ul><li>Purpura fulminans </li></ul>
  16. 19. Cardiovascular Signs <ul><li>“ Warm shock” -  CO,  SVR </li></ul><ul><li>“ Cold shock” -  CO,  SVR </li></ul><ul><li>Anaerobic metabolism - lactic acidemia </li></ul><ul><li>Myocardial depressant factor - ?? </li></ul>
  17. 20. Pulmonary Signs <ul><li>Tachypnea </li></ul><ul><li>Hyperventilation, respiratory alkalosis </li></ul><ul><li>ARDS, respiratory failure </li></ul><ul><li>Ventilation-perfusion mismatch </li></ul><ul><li>Widened alveolar-arterial oxygen gradient </li></ul><ul><li>Reduced lung compliance </li></ul>
  18. 21. Hematologic Findings <ul><li>Neutrophilic leukocytosis </li></ul><ul><li>Leukemoid reaction </li></ul><ul><li>Neutropenia </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Toxic granulations </li></ul><ul><li>DIC </li></ul>
  19. 22. Renal and Gastrointestinal Signs <ul><li>Acute tubular necrosis, oliguria, anuria </li></ul><ul><li>Upper GI bleeding </li></ul><ul><li>Cholestatic jaundice </li></ul><ul><li>Increased transaminase levels </li></ul><ul><li>Hypoglycemia </li></ul>
  20. 23. Acute Physiology and Chronic Health Evaluation <ul><li>APACHE II </li></ul><ul><li>Temp Arterial pH </li></ul><ul><li>MAP Serum Na; Serum Cr </li></ul><ul><li>Heart rate Hematocrit </li></ul><ul><li>Resp. rate WBC </li></ul><ul><li>Oxygenation Glasgow Coma Score </li></ul><ul><li>Acute physiology score + Age + Chronic health points </li></ul>
  21. 24. Laboratory Studies <ul><li>Blood cultures </li></ul><ul><li>Infected secretions/body fluids </li></ul><ul><li>Stool for WBC, C. difficile </li></ul><ul><li>Aspirate advancing edge of cellulitis </li></ul><ul><li>Skin biopsy/scraping </li></ul><ul><li>Buffy coat </li></ul>
  22. 25. Therapy of Septic Shock <ul><li>Correct pathologic condition </li></ul><ul><li>Optimize intravascular volume </li></ul><ul><li>Administer empiric antimicrobial therapy </li></ul><ul><li>Administer vasoactive drugs </li></ul>
  23. 26. Failure of Fluid Replacement and Vasopressors <ul><li>acidosis - pH<7.3 </li></ul><ul><li>hypocalcemia </li></ul><ul><li>adrenal insufficiency </li></ul><ul><li>hypoglycemia </li></ul>
  24. 27. Empiric Antimicrobial Regimens for Sepsis Syndrome <ul><li>Community-acquired non-neutropenic </li></ul><ul><ul><li>Urinary tract: 3rd generation cepholosporin, piperacillin, quinolone + AG </li></ul></ul><ul><ul><li>Non-urinary tract: 3rd generation cepholosporin + metronidazole,  -lactam/  -lactamase inhibitor + AG </li></ul></ul>
  25. 28. <ul><li>Hospital-acquired </li></ul><ul><ul><li>Nonneutropenic: 3rd generation cephalosporin + metronidazole,  -lactam /  -lactamase inhibitor, menopenem all + AG </li></ul></ul><ul><ul><li>Neutropenic: Timentin + AG, meropenem + AG; ceftazidime + metronidazole + AG </li></ul></ul>
  26. 29. Septic Shock Outcomes for Patients on Hospital Wards versus ICU’s <ul><li>Ward patients: Delays in ICU transfer (67 mins.) </li></ul><ul><li>IV fluid boluses (27 vs 15 mins.) </li></ul><ul><li>Inotropic agents (310 vs 22.5 mins) </li></ul><ul><li>Mortality: Wards (70%) vs ICUs (39%) </li></ul><ul><li>Apache II scores (18.5 vs 24) </li></ul><ul><li>Candidemia </li></ul>JS Lunberg, Crit. Care Med. 26:1020; 1998
  27. 30. Immunotherapies for Septic Shock <ul><li>Corticosteroids </li></ul><ul><li>Antiendotoxin monoclonal antibodies E-5, HA-1A </li></ul><ul><li>Anti-TNF antibodies </li></ul><ul><li>IL-1 receptor antagonists </li></ul>
  28. 31. Other Treatment Modalities <ul><li>Granulocyte transfusions </li></ul><ul><li>Recombinant colony-stimulating factors </li></ul><ul><li>Diuretics </li></ul><ul><li>Pentoxifylline, ibuprofen, naloxone </li></ul><ul><li>Oral nonabsorbable antimicrobial agents </li></ul>
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