Intended for healthcare professionals

Practice Rational Testing

Investigating sepsis with biomarkers

BMJ 2015; 350 doi: (Published 28 January 2015) Cite this as: BMJ 2015;350:h254

This article has a correction. Please see:

  1. Anthony S McLean, professor of intensive care medicine1,
  2. Benjamin Tang, associate professor of intensive care medicine1,
  3. Stephen J Huang, associate professor and principal research fellow, intensive care medicine12
  1. 1Department of Intensive Care Medicine, University of Sydney, Sydney, NSW, Australia
  2. 2Nepean Hospital, Sydney, NSW, Australia
  1. Correspondence to: A S McLean Department of Intensive Care Medicine, Nepean Hospital, University of Sydney, Sydney NSW, Australia anthony.mclean{at}

The bottom line

  • The diagnosis of sepsis is a challenge, and the causative pathogen is not always identified

  • Clinical assessment remains the mainstay of diagnosis of sepsis, with tests such as white cell count, C reactive protein, lactate, and procalcitonin being adjunctive

  • Biomarkers such as lactate and procalcitonin have only moderate diagnostic performance and are also raised in non-infectious conditions

A 65 year old man presents with lethargy, fever, and rigors. On examination his arterial blood pressure is 120/50 mm Hg, he has a mild tachycardia (105 beats/min), and he is febrile (38.7°C), with no other abnormalities. His urine is cloudy and urinary dipstick test shows the presence of leucocytes and nitrate. There is no history of recent travel, urinary symptoms, or drug allergy (including antibiotic sensitivity) and no relevant findings on systems review (such as liver or kidney disease). You promptly establish intravenous access, draw blood for laboratory tests (including blood culture), send a urine sample for microbiology, and administer the first dose of an empirical broad spectrum antibiotic.

These clinical signs and symptoms strongly suggest sepsis. However, in a third of patients with sepsis, the causative pathogen cannot be identified.1 The lack of confirmatory evidence of infection often makes the diagnosis of sepsis a challenge. This difficulty is reflected by the inclusion of the words “probable infection” in defining sepsis in the Surviving Sepsis Campaign guidelines (box 1).2

Box 1: Definitions and classification of sepsis syndrome2

Systemic inflammatory response syndrome

An abnormal increase in two or more of the following parameters:

  • White …

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