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
SIRS
SEVERE SEPSIS 3

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

5. SIRS = systemic inflammatory response syndrome
The Sepsis Continuum
Sepsis
SIRS
Severe
Septic
Shock
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/mm3 or <4,000/mm3 or >10% bands
SIRS with a
presumed
or confirmed
infectious
process
Sepsis with
organ failure
Refractory
hypotension
SIRS = systemic inflammatory response syndrome
Chest 1992;101:1644. 5

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: Cardiac Dysfunction
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 10

11. High Risk Patients For Sepsis For Dying For Both
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

15. Fig. 56.1 Potential risk factors leading to sepsis.15

16. Fig. 56. 2 Positive blood cultures in severe sepsis
Fig Positive blood cultures in severe sepsis. Data from Bochud et al.42 16

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

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

19. 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%

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

21. 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

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

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

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

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