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

Not available.

Discussion

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

Sepsis:

" 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.

References

Singer, Mervyn, et al. "The third international consensus definitions for sepsis and septic shock (sepsis-3)." Jama 315.8 (2016): 801-810.

Bone, Roger C., William J. Sibbald, and Charles L. Sprung. "The ACCP-SCCM consensus conference on sepsis and organ failure." CHEST journal 101.6 (1992): 1481-1483.

Bone, Roger C., et al. "Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis." Chest 101.6 (1992): 1644-1655.

Abraham, Edward. "New Definitions for Sepsis and Septic Shock: Continuing Evolution but With Much Still to Be Done." JAMA 315.8 (2016): 757-759.

Lynn, Lawrence A. "The diagnosis of sepsis revisited-a challenge for young medical scientists in the 21st century." Patient safety in surgery 8.1 (2014): 1.

Pauker, Stephen G., and Jerome P. Kassirer. "The threshold approach to clinical decision making." New England Journal of Medicine 302.20 (1980): 1109-1117.

Beesley, Sarah J., and Michael J. Lanspa. "Why we need a new definition of sepsis." Annals of translational medicine 3.19 (2015).

Kaukonen, Kirsi-Maija, et al. "Systemic inflammatory response syndrome criteria in defining severe sepsis." New England Journal of Medicine 372.17 (2015): 1629-1638.

Simpson, Steven Q. "New Sepsis Criteria: A Change We Should Not Make." Chest 149.5 (2016): 1117-1118.

Seymour, Christopher W., et al. "Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)." Jama 315.8 (2016): 762-774.

Shankar-Hari, Manu, et al. "Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3)." Jama 315.8 (2016): 775-787.

R.Daniels et al. "Interim statement regarding the new international consensus definitions of sepsis" UK Sepsis Trust (2016)

Sinha, Sharmili, and Banambar Ray. "Sepsis-3: How useful is the new definition?." Journal of anaesthesiology, clinical pharmacology 34.4 (2018): 542.