Question 27

Briefly outline the difficulties encountered in the clinical and laboratory  diagnosis of sepsis in the critical care unit.

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College Answer

a) Fever and other SIRS criteria have low specificity 
b) No specific clinical signs of sepsis apart from specific syndromes such as endocarditis 
c) Elderly, immunocompromised and malnourished patients-do not manifest typical signs of sepsis 
d) Both infective and non infective causes of SIRS may coexist in the same patient and therefore presence of inflammation not always a reliable sign. 
e) Deep seated collections difficult to diagnose

a) Leukocytosis not specific as it is a marker of stress rather than infection 
b) Reliable diagnosis established by presence of organisms only in blood or in sterile tissues; but tissues may be difficult to obtain 
c) Administration of antibiotics frequently before diagnostic tests limits utility of cultures 
d) Cultures might sometimes take time for positive results to come back 
e) Tests such as PCR might not be universally available 
f) Serology tests frequently non specific 
g) Biomarkers such as procalcitonin and CRP and IL-6 do not have a high sensivity and specificity. 
h) Lack of consensus on criteria regarding what constitutes ventilator associated pneumonia, line sepsis etc.


My own attempt to rewrite the answer to this question is non-superior to the college answer. It is surprisingly difficult to find any article which complains about how difficult it is to make the diagnosis of sepsis.

Clinical criteria for SIRS have poor specificity for sepsis

  • Not all septic patients are febrile or hypothermic. Many are normothermic.
  • Tachycardia can represent hypovolemia, anxiety, pain, or inotrope effect.
  • Tachypnoea may represent anxiety, pain or aseptic metabolic acidosis
  • Some patient groups will not be able to manifest clinical features of SIRS:
    • Malnourished patients
    • Immunocompromised
    • Therapeutically cooled
    • Elderly patients
    • Hypothyroid patients
  • Infectious and non-infectious causes of SIRS may co-exist

Infectious source may be unclear

  • The patient is sedated and cannot participate in history-taking.
  • There are no generic features of 'infection" to look for.
  • Specific features of infection may be obscured by other clinical findings
  • Criteria for the diagnosis of an infectious source are frequently not available (eg. central line associated bacteraemia, ventilator-associated pneumonia, etc).
  • Clinical features of specific syndromes may be shared by non-infectious pathology (eg. purpura fulminans)

The laboratory markers of sepsis are non-specific

  • All biochemical markers of sepsis can become elevated due to non-infectious causes.
  • Serology tests and PCR studies may not be organism-specific, or may require convalescent samples.
  • Microbiology is unreliable, because:
    • Sample may be difficult to obtain
    • Organism may be difficult to culture (eg. Treponema pallidum)
    • Sample may be sterilised by antibiotic therapy
    • A positive sample culture may represent colonisation rather than infection.
    • Cultures take time to develop, whereas sepsis evolves rapidly - empiric therapy must be commenced long before microbiology is available.


Claessens, Yann-Erick, and Jean-François Dhainaut. "Diagnosis and treatment of severe sepsis." Critical Care 11.Suppl 5 (2007): S2.


Lynn, Lawrence A. "The diagnosis of sepsis revisited-a challenge for young medical scientists in the 21st century." Patient safety in surgery 8 (2014): 1.


Vandijck, D. M., J. M. Decruyenaere, and S. I. Blot. "The value of sepsis definitions in daily ICU-practice." Acta Clinica Belgica 61.5 (2006): 220-226.