Sepsis Syndrome

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Sepsis Syndrome

• By Dr. Sabir M. Ameen

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Sepsis and Septic Shock

• 13th leading cause of death in U.S.
• 500,000 episodes each year
• 35 mortality
• 30-50 culture-positive blood

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What is SIRS?

• A systemic response to a nonspecific insult
• Infection, trauma, surgery, massive transfusion,
  etc
• Defined as ?2 of the following
• Temperature gt38.3 or lt36 0C
• Heart rate gt90 min-1
• Respiratory rate gt20 min-1
• White cells lt4 or gt12
• Acutely altered mental state
• Hyperglycaemia (BMgt7.7) in absence of DM

SEVERE SEPSIS
SIRS
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Definitions

• Sepsis SIRS Infection
• Infection either
• Bacteraemia (or viraemia / fungaemia /protozoan)
• Septic focus (abscess / cavity / tissue mass)

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The Sepsis Continuum

• A clinical response arising from a nonspecific
  insult, with ?2 of the following
• T gt38oC or lt36oC
• HR gt90 beats/min
• RR gt20/min
• WBC gt12,000/mm3 or lt4,000/mm3 or gt10 bands

• SIRS with a
• presumed
• or confirmed
• infectious
• process

Sepsis with organ failure
Refractory hypotension
SIRS systemic inflammatory response syndrome
Chest 19921011644.
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Definitions Cont.

• Severe sepsis Sepsis Organ Dysfunction
• Organ Dysfunction Any of
• SBP lt90 or inotrope to get MAP 90
• BE lt-5mmol/L
• Lactate gt2mmol/L
• Oliguria lt30ml/hr for 1 hour
• Creatinine gt0.16mmol/L
• Toxic confusional state
• FIO2 gt0.4 and PEEP gt5 for oxygenation

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Definitions Cont.

• Septic Shock Severe sepsis Hypotension
• Hypotension either
• SBP lt90
• Inotrope to get MAP gt90

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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

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• 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)

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Wheres the infection ?
Bernard Wheeler NEJM 336912, 1997
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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

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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

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Multiple Organ Dysfunction Syndrome

• Dysfunction of 2 or more systems
• Four or more system dysfunction - mortality near
  100

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Factors Associated with Highest Mortality

• Respiratory gt abdominal gt urinary
• Nosocomial infection
• Hypotension, anuria
• Isolation of enterococci or fungi
• Gram-negative bacteremia, polymicrobial
• Body T lt 38C
• Age gt 40
• Underlying illness cirrhosis or malignancy

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Laboratory Studies

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

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Therapy of Septic Shock

• Correct pathologic condition
• Optimize intravascular volume
• Empiric antimicrobial therapy
• Vasoactive drugs

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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

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Failure of Fluid Replacement and Vasopressors

• acidosis pH lt7.3
• hypocalcemia
• adrenal insufficiency
• hypoglycemia

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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

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Empiric Antimicrobial Regimens for Sepsis Syndrome

• Community-acquired non-neutropenic
• UTI 3rd generation cepholosporin
• Non-urinary tract 3rd generation cepholosporin
  metronidazole

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• Hospital-acquired
• Non-neutropenic 3rd generation cephalosporin
  metronidazole aminoglycoside
• Neutropenic meropenem aminoglycoside

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Immunotherapies for Septic Shock

• Corticosteroids
• Anti-endotoxin monoclonal antibodies
• Anti-TNF antibodies
• IL-1 receptor antagonists

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Other Treatment Modalities

• Granulocyte transfusions
• Recombinant colony-stimulating factors
• Diuretics
• Pentoxifylline, ibuprofen, naloxone
• Oral nonabsorbable antimicrobial agents