Question 22

a)    What is the current Sepsis-3 definition of sepsis and septic shock?    (20% marks)

b)    Discuss the challenges of developing definitions for sepsis and septic shock, and the advantages of standardised definitions.    (80% marks)

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College answer

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a) Sepsis-3 definitions of sepsis and septic shock:


" life-threatening organ dysfunction due to a dysregulated host response to infection "

Organ dysfunction:

An increase of 2 points or more of the SOFA score
( every 2 points = 10% mortality)
A "quick SOFA" consists of three domains:

  • Hypotension: SBP < 100 mmHg
  • Altered mental status: any GCS less than 15
  • Tachypnoea: respiratory rate > 22
Septic shock:

Sepsis as above, as well as both:

  • Hypotension requiring vasopressors
  • Lactate over 2 mmol/L

(both criteria met = 40% mortality)

Advantages of standard definitions:

  • Theoretical arguments for the utility of strict definitions
    • Theoretical medicine requires strict definitions to separate patients into a "disease" group, to compare them to a "no disease" group
    • Standardisation of definitions is required to ensure a common language, to facilitate communication between clinicians and researchers
    • Standard definitions allow comparative evaluation of different therapies; without such definitions comparison between studies and their meta-analysis would be difficult.
  • Pragmatic arguments for defining sepsis
    • Sepsis is a disease entity with significant mortality, and this mortality decreases with early detection and treatment.
    • Ergo, some of this mortality is due to a failure of early detection, and early detection would be facilitated by a set of diagnostic criteria that can be used to identify sepsis

Challenges of creating standard definitions for sepsis:

  • Challenges of "sepsis" as a concept
    • Sepsis is non-specific and its manifestations are protean
    • It would be impossible to strictly and objectively define every possible permutation of sepsis
    • There is no gold standard test to compare any new definition against
    • Use of subjective elements to broaden the definition (eg. "suspected infection") reduces its validity
  • Challenges in the use of biomarkers and clinical findings as criteria:
    • Some, eg. lactate, favour resource-rich environments, where lactate testing is possible
    • Some fail to distinguish between new and pre-existing organ dysfunction (eg. qSOFA)
    • The cut-offs for organ dysfunction scores are usually chosen arbitrarily. For the most, they do not represent any genuine physiologically relevant thresholds
    • Some, eg. SOFA and qSOFA are not well known outside of the ICU community, and decrease in their validity outside the ICU
  • Challenges in the very process of creating definitions:
    • Delphi process encourages the suppression of outlier opinions, and promotes a trend towards mediocrity
    • Without an objective definition, worldwide sepsis mortality is on a decline, which makes it difficult to justify creating a new definition
    • Multiple possible stakeholder groups could claim they deserve to have input on the definition (intensivists, ED physicians, ID specialists), which makes it more difficult to achieve consensus
    • The new definitions would have to be comparable with old definitions, otherwise one risks the inability to compare new research with old research studies.


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