Transcript 08_-_Sepsis_Syndrome

Sepsis Syndrome
By: Dr. Sabir M. Ameen
Sepsis and Septic Shock
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13th leading cause of death in U.S.
500,000 episodes each year
35% mortality
30-50% culture-positive blood
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
Definitions
• Sepsis = SIRS + Infection
• Infection = either
• Bacteraemia (or viraemia / fungaemia /protozoan)
• Septic focus (abscess / cavity / tissue mass)
The Sepsis Continuum
SIRS
Sepsis
 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
Severe
Sepsis
Septic
Shock
Sepsis with
organ failure
Refractory
hypotension
SIRS = systemic inflammatory
response syndrome
Chest 1992;101:1644.
Definitions Cont.
• Severe sepsis = Sepsis + Organ Dysfunction
• Organ Dysfunction = Any of
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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
Definitions Cont.
• Septic Shock = Severe sepsis + Hypotension
• Hypotension = either
• SBP <90
• Inotrope to get MAP >90
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’
• 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)
Where’s the infection ?
Abdomen
15%
Urine
10%
Lung
47%
Bernard & Wheeler NEJM 336:912, 1997
Other
8%
Culture
Negative
20%
High Risk Patients
• For Sepsis
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Post op / post procedure / post trauma
Post splenectomy (encapsulated organisms)
Cancer
Transplant / immune suppressed
Alcoholic / Malnourished
• For Dying
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Genetic predisposition (e.g. meningococcus)
Delayed appropriate antibiotics
Yeasts and Enterococcus
Site
• For Both
– Cultural or religious impediment to treatment
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
Multiple Organ Dysfunction
Syndrome
• Dysfunction of 2 or more systems
• Four or more system dysfunction mortality near 100 %
Factors Associated with
Highest Mortality
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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
Laboratory Studies
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Blood cultures
Infected secretions/body fluids
Stool for WBC, C. difficile
Aspirate advancing edge of cellulitis
Skin biopsy/scraping
Buffy coat
Therapy of Septic Shock
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Correct pathologic condition
Optimize intravascular volume
Empiric antimicrobial therapy
Vasoactive drugs
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%
Failure of Fluid Replacement and
Vasopressors
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acidosis – pH <7.3
hypocalcemia
adrenal insufficiency
hypoglycemia
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
Empiric Antimicrobial Regimens
for Sepsis Syndrome
• Community-acquired non-neutropenic
– UTI: 3rd generation cepholosporin
– Non-urinary tract: 3rd generation
cepholosporin + metronidazole
• Hospital-acquired
– Non-neutropenic: 3rd generation cephalosporin +
metronidazole + aminoglycoside
– Neutropenic: meropenem + aminoglycoside
Immunotherapies for
Septic Shock
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Corticosteroids
Anti-endotoxin monoclonal antibodies
Anti-TNF antibodies
IL-1 receptor antagonists
Other Treatment Modalities
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Granulocyte transfusions
Recombinant colony-stimulating factors
Diuretics
Pentoxifylline, ibuprofen, naloxone
Oral nonabsorbable antimicrobial agents