Sepsis and Septic Shock

Definitions pertaining to sepsis and septic shock

  • Infection:  inflammatory response to microorganisms or an invasion of normally sterile tissues
    • Urine & CSF are both fluids that are supposed to be sterile
    • Inflammation=increase in white count and/or fever
  • SIRS (Systemic inflammatory response syndrome): response to infection, but doesn’t have to be an infection  (trauma, burns, pancreatitis, etc) Characterized by having >2 of the following manifestations
    • HR > 90 BPM
    • Respirations > 20/min or PaCO2 < 32 mmHg
    • Not always an increase in temp or white count
      • Temp > 38 C or < 36 C
      • WBCs > 12,000 or < 4,000
    • Infection can cause hypothermia in some patients
    • Patients fighting infection can have decrease WBC due to response
  • Sepsis:  an infection + > 2 SIRS criteria listed above.
    • Note sepsis can be self-limiting & doesn’t always require antibiotics & may not always be life-threatening
  • Severe sepsis = sepsis + organ dysfunction
    • Results from systemic inflammation + coagulation + impaired fibrinolysis
    • All organs can be affected  (most commonly CV, kidneys but look out for metabolic acidosis & decreased platelet counts)
    • Marked by a Decrease in (APC) activated protein C (protein C helps in anticoagulation, fibrinolysis & reversing hypotension)
      • In addition to Activated Protein C, other important pro-inflammatory players are tissue factor (TF) & pro-inflammatory cytokines (IL-1B, IL-6, TNF-alpha))
      • In addition to activated Protein C, other important coagulation players are clotting factors 2A, 5A & 8A
      • In addition to activated Protein C, other important fibrinolysis players are tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) & thrombin-activatable fibrinolysis inhibitor (TAF-I)
      • Functions of Activated Protein C (APC)
        • Decrease coagulation & inflammation
          • Limits TNF-alpha & IL-1 Production
          • Interferes with LPS-CD14 interaction
          • Inhibits E-Selectin-mediated inflammation
        • Increases Fibrinolysis
          • Inhibits thrombin production
          • Inhibits thrombin-mediated inflammation
          • Inhibits PAI-1 & TAFI-alpha activation

Septic shock = sepsis + hypotension (low BP)despite fluid restriction  (if the pt responds to fluid therapy, it’s not septic shock)

  • MODS (multiple organ dysfunction syndrome) = altered organ (kidney) function as a result of sepsis   (may not fully regain renal function after infection is gone)

Clinical presentation of sepsis and septic shock

  • Sepsis is usually caused by an underlying disease (neutropenia, DM, renal failure, alcoholism/cirrhosis, respiratory failure) or an enormous release of endotoxin (due to antibiotic killing a microorganism)
    • 25% of sepsis is caused by gram +, 25% is caused by gram -, 30% is caused by an unidentifiable organism
      • Zosyn + levaquin + vanco = common empiric regimen until organism is indentified
        • If the cultured bacteria comes back gram +, then you can remove zosyn or levaquin which have gram – coverage
    • Endotoxin is released from gram – bacteria (gram + don’t release endotoxin); it isn’t toxic itself but it triggers a cascade release of primary & secondary inflammatory mediators.  If the body’s response to the mediators is too aggressive, severe sepsis or even shock can occur
      • Endotoxin causes the release of inflammatory mediators (NO gets formed causing blood vessels to dilate & hypotension results)
  • Septic shock:
    • Early shock stage (sepsis-induced hypotension)
      • Increased CO & decreased systemic vascular resistance (BP < 90 mmHg or a reduction of > 40 mmHg from baseline)
    • Late shock stage (hypotension + perfusion abnormalities)
      • Normalized/decreased CO + hypotension despite adequate fluid + perfusion abnormalities (lack of oxygen to fingers/toes/kidneys/organs)
    • Complications of septic shock:  MODS (multiple organ dysfunction syndrome)
      • Kidneys, liver, cardio-respiratory, adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC)

Analyze and recommend treatment for both sepsis & septic shock

  • Sepsis:  source control & antibiotics;  mechanical ventilation, renal replacement therapy, sedation/analgesia, adequate nutrition & hematological support may also be necessary though.
    • Can be caused by either gram negative (E. Coli, Klebsiella, Pseudomonas, serratia, enterobacter, proteus) or gram positive organisms  (Staph aureus, Staph pneumoniae)
      • E. Coli is a very common cause & very easy to treat.  Gram + overall are easier to treat though.  As you from left to right as listed above, sepsis becomes more difficult to treat.
  • Severe sepsis:  APC  (Xigris) + everything above
    • Activated Protein C (APC) reduces coagulation, increases fibrinolysis & decreases inflammation
      • Decreases mortality in pts w/ severe sepsis & a high risk of death
      • Dose:  24 mcg/kg/hr for 96 hours (doesn’t need to be uninterrupted but it’s preferred.)
        • based on actual body weight
        • No need for dose adjustments
        • Stop if clinically important bleeding exists
  • Septic shock:  everything above + fluid resuscitation + vasoactive drug therapy + corticosteroids
    • Fluid resuscitation:  crystalloid (ex. NS) or colloid (ex. albulmin, hetastarch) infusion
    • Vasoactive drug therapy:  pt/disease driven dosing (EPI, NE, phenylephrine, dopamine)
      • Use these if fluid resuscitation doesn’t work
      • Dobutamine isn’t a vasopressor, it’s an inotrope (it has more beta-2 activity than alpha-1 activity) and should NOT be used in sepsis
      • Dopamine:  use in high doses–>  i.e > 10-20 mcg/kg/min (active in the periphery; mid dose:  5-10 mcg/kg/min {inotropic};  low dose: 1-4 mcg/kg/min {active in kidney})
        • At lower doses, it’s more of inotrope while at higher doses it’s more of a vasoconstrictor
      • NE: 2-20 mcg  (both an inotrope & vasopressor/constrictor)
      • **Phenylephrine: 50-300 mcg/min  (just a vasopressor/constrictor)
    • Corticosteroids:  may be useful in pts w/ secondary adrenal insufficiency (also thought to conserve Na & H2O)

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