What is Sepsis?  The Sepsis Paradigm

     
       

 

         
       
  • The patient is initially injured in some way – this may be, for example, infection, trauma or inflammation.
  • The result of this injury is activation of host defense mechanisms, including release of inflammatory cytokines, particularly interleukin-6 and tumor necrosis factor alpha.
  • The physiologic manifestations of this process include tachypnea, tachycardia, leucocytosis and pyrexia, and we call this the systemic inflammatory response. The body is, in effect, responding to the source of inflammation and making physiologic compensation for the systemic upset.
  • If the patient is unable to adequately compensate, and suffers acute organ failure, then he /she requires critical care interventions – usually mechanical ventilation, often with cardiovascular support.
  • The patient has undergone a “first hit”. He/she is now vulnerable to further injury.
  • At this point one of three things may happen: 1) the injury and inflammatory and or inflammatory response may persist (26). 3) The patient may develop a second (or third or fourth) injury, such as nosocomial pneumonia, ventilator induced lung injury or bacterial translocation from the gut, which stokes up the inflammatory response.
  • Persistent inflammation leads to widespread endothelial dysfunction, and ischemic tissue injury (due to hypotension, intravascular thrombosis, tissue edema, abnormal oxygen extraction etc).
  • The result of this is sequential organ damage – multi organ dysfunction. Examples of this are an increase in the alveolar to arterial oxygen gradient, a reduced ejection fraction, agitation or coma, a reduction in creatinine clearance, and increase in serum bilirubin, a decrease in platelets and clotting factors etc.
  • As the disease process progresses, multi-organ dysfunction becomes multi-organ failure. This is characterized by the requirement for external interventions to maintain homeostasis – mechanical ventilation, inotropes and vasopressors, renal replacement therapy, continuing blood product transfusions etc.
  • The patient becomes severely catabolic, physiologic reserve deteriorates and neuroendocrine exhaustion occurs. The latter is characterized by the inability of the patient to mount an appropriate endocrine response to ongoing  stress and inflammation.
  • The majority of patients who develop multi organ failure succumb, due to inability to wean external interventions (usually mechanical ventilation and vasopressors).
  • Death is inevitably as a result of withdrawal of this support.
 

References

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THIS TUTORIAL BY PATRICK NELIGAN MD, UNIVERSITY OF PENNSYLVANIA

       
       

 

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