Sepsis – Pathology

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Pathophysiology

Is a complication of any known infection that results in a systematic inflammatory response (SIRS) or organ dysfunction.  Its effects lie on a continuum of tissue injury.  The inflammatory response affects the circulation by several mechanisms including vasodilatation, capillary leak and myocardial depression.  The severest form manifests as septic shock.  When this occurs mortality exceeds 40%.

Diagnostic criteria

  • The challenge of developing defined criteria for sepsis is that some of its pathological manifestations have overlap with other insults.  SIRS or organ dysfunction can occur in other situations apart from infection or in conjunction with it.
  • Using microbiological criteria is also difficult because some patients with apparent sepsis and septic shock are culture negative even though there is good clinical evidence of an infection taking place.
  • The identification of early shock or organ hypo perfusion is also difficult because no one haemodynamic parameter is adequate to determine this
  • Lastly, the manifestations of sepsis may not be apparent initially on the patient’s presentation or before any microbiological identification has occurred.  It requires ongoing vigilance and a combination of serial clinical assessment and laboratory data to determine if it is occurring.
  • Sepsis-2 and more recently, Sepsis-3 have been two international consensus statements to define this.
  • Currently there is no highly accurate test with both high sensitivity and specificity.  There will always be the possibility of false positives and false negatives.  Too low a trigger will results in excessive antibiotic use, too high and the missed opportunity to prevent serious morbidity or mortality to the patient.

Management – proven measures that reduce morbidity and mortality

  • Early administration of antibiotics for bacterial infection
  • Circulatory support including vasopressors if evidence of shock
  • Prompt surgical debridement or drainage of infected tissue

Controversies and clinical challenges

  • Alternative biomarkers to diagnose or govern therapy
  • Excessive fluid administration and its relations to Acute lung Injury and Adult Respiratory Distress syndrome (see Fluid responsiveness)
  • Type and timing of resuscitation fluid (see SAFE Study)
  • Timing of use of vasopressor
  • Haemodynamic targets for individual patients (see Goal-Directed Therapy)
  • The role, timing and dosing of immuno-modulators such as steroids
  • The role of early renal replacement therapy to remove inflammatory mediators
  • Operational definitions of sepsis in resource-poor countries without laboratory support

See Sepsis – One Practical Approach

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