Sepsis Syndrome

1. Sepsis Syndrome By: Dr. Sabir M. Ameen

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. What is SIRS? A systemic response to a nonspecific insult Infection, trauma, surgery, massive transfusion, etc Defined as 2 of the following: Temperature >38.3 or <36 0C Heart rate >90 min-1 Respiratory rate >20 min-1 White cells <4 or >12 Acutely altered mental state Hyperglycaemia (BM>7.7) in absence of DM SEVERE SEPSIS SIRS

4. Definitions • Sepsis = SIRS + Infection • Infection = either • Bacteraemia (or viraemia / fungaemia /protozoan) • Septic focus (abscess / cavity / tissue mass)

5. The Sepsis Continuum A clinical response arising from a nonspecific insult, with 2 of the following: T >38oC or <36oC HR >90 beats/min RR >20/min WBC >12,000/mm3or <4,000/mm3 or >10% bands Severe Sepsis Septic Shock SIRS Sepsis SIRS with a presumed or confirmed infectious process Sepsis with organ failure Refractory hypotension SIRS = systemic inflammatory response syndrome Chest 1992;101:1644.

6. Definitions Cont. • Severe sepsis = Sepsis + Organ Dysfunction • Organ Dysfunction = Any of • SBP <90 or inotrope to get MAP 90 • BE <-5mmol/L • Lactate >2mmol/L • Oliguria <30ml/hr for 1 hour • Creatinine >0.16mmol/L • Toxic confusional state • FIO2 >0.4 and PEEP >5 for oxygenation

7. Definitions Cont. • Septic Shock = Severe sepsis + Hypotension • Hypotension = either • SBP <90 • Inotrope to get MAP >90

8. Pathophysiology Infection of bacterial, viral or fungal origin Nidus of infection through multiplication of infective organism, releasing various mediators which consist of structural components of the organism and/or exotoxins and endotoxins (from the dead invading organism) Over 100 mediators have been identified (include: tissue necrosis factors, interleukins) Circulatory & cardiac ‘toxic’

9. Circulatory changes: • Nitric oxide overproduction in response to these mediators results in peripheral vasodilatation, decreased systemic vascular resistance, fluid leak from capillaries • Capillary blood flow is reduced • Cardiac Dysfunction • Ventricular dilatation with decreased ejection fraction, decreased stroke volume • Leads to increased heart rate (& O2 demand)

10. Where’s the infection ? Bernard & Wheeler NEJM 336:912, 1997

11. High Risk Patients • For Sepsis • Post op / post procedure / post trauma • Post splenectomy (encapsulated organisms) • Cancer • Transplant / immune suppressed • Alcoholic / Malnourished • For Dying • Genetic predisposition (e.g. meningococcus) • Delayed appropriate antibiotics • Yeasts and Enterococcus • Site • For Both • Cultural or religious impediment to treatment

12. CLINICAL EFFECTS OF INFECTION ON THE BODY Acute • Fever; anorexia, protein catabolism, acute-phase protein response, hypoalbuminaemia, low serum iron, anemia, neutrophilia • Inflammation; pain, dysfunction, tissue damage • Convulsions; especially in children • Confusion; especially in the elderly • Shock; fall in circulating blood volume associated with lowered systemic vascular resistance • Blood; hemorrhage, haemolytic anemia, intravascular coagulation • Organ failure; kidneys, liver, lung, heart, brain, necrosis of skin

13. Multiple Organ Dysfunction Syndrome • Dysfunction of 2 or more systems • Four or more system dysfunction - mortality near 100 %

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

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

17. Therapy of Septic Shock • Correct pathologic condition • Optimize intravascular volume • Empiric antimicrobial therapy • Vasoactive drugs

18. Initial resuscitation of sepsis: therapeutic goals Central venous pressure: 8 – 12 mmHg Mean arterial pressure: ≥ 65 mmHg Urine output: 0.5 ml/kg/h Central venous (SVC) or mixed venous oxygen saturation: ≥ 70%

19. Failure of Fluid Replacement and Vasopressors • acidosis – pH <7.3 • hypocalcemia • adrenal insufficiency • hypoglycemia

20. Choosing antibiotics in sepsis There is no, single, “best” regimen Consider the site of the infection Consider which organisms most often cause infection at that site Choose antibiotic(s) with the appropriate spectrum After obtaining cultures, give antibiotics quickly and empirically at appropriate dose

21. Empiric Antimicrobial Regimens for Sepsis Syndrome • Community-acquired non-neutropenic • UTI: 3rd generation cepholosporin • Non-urinary tract: 3rd generation cepholosporin + metronidazole

22. Hospital-acquired • Non-neutropenic: 3rd generation cephalosporin + metronidazole + aminoglycoside • Neutropenic: meropenem + aminoglycoside

23. Immunotherapies for Septic Shock • Corticosteroids • Anti-endotoxin monoclonal antibodies • Anti-TNF antibodies • IL-1 receptor antagonists

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