Sepsis is one of the leading causes of death worldwide but remains a little known entity to the general public. Every year, around 150,000 people in the UK develop sepsis and, of those, over 40,000 die. The incidence of sepsis in the developed world is increasing by an alarming rate of 8-13% per year. It is now a commoner diagnosis than myocardial infarction and claims more lives annually than breast and bowel cancer combined. Sepsis is one of the most important and challenging problems facing the modern physician.

What is Sepsis?

Sepsis arises when the body’s response to an infection injures its own tissues and organs. It may lead to shock, multiple organ failure, and death, especially if not recognized early and treated promptly. It can be caused by a wide variety of infectious agents, but the vast majority of cases are caused by bacteria that are commonly encountered by most people on a day-to-day basis.

It remains the primary cause of death from infection despite advances in modern medicine, including vaccines, antibiotics, and acute care with hospital mortality rates between 30 and 60%.


The Surviving Sepsis Campaign

The surviving sepsis campaign is a joint collaboration between the Society of Critical Care Medicine and the European Society of Intensive Care. It was initiated in 2002 and the first set of guidelines was published in 2004. Last year the third incarnation of the guidelines was released and they included some notable changes from previous versions.

The previous guidelines relied heavily on the concept of the systemic inflammatory response syndrome (SIRS), an inflammatory state that affects the entire body that is often due to a response of the immune system to infection.


The SIRS criteria were:

  • Temperature < 36°C or > 38°C
  • Heart rate > 90/min
  • Respiratory rate > 20/min (or PaCO2 < 4.3 kPa)
  • White cell count < 4 x 109, > 12 x 109, or > 10% bands


Sepsis was defined as the presence of > 2 SIRS criteria in the presence of a suspected source of infection.

Severe sepsis was defined as sepsis in the presence of evidence of organ dysfunction.

Septic shock was defined as severe sepsis in the presence of tissue hypoperfusion persisting an hour after resuscitation with intravenous fluids.

These definitions, however, were far from perfect. Infection is not the only thing that can cause SIRS, and many experts considered the SIRS criteria to be overly sensitive. A significant number of patients presenting to the Emergency Department and nearly all admitted to Intensive Care meet the criteria, and many of these have no evidence of infection at all.


Enter Sepsis 3.0

In February 2016 the Society of Critical Care Medicine published a JAMA article reformatting the definitions of sepsis in an attempt to overcome the shortcomings of the old definitions. It is worth mentioning at this point that these changes have been somewhat controversial and are not currently endorsed by any Emergency Medicine Society. The main changes are a new definition of sepsis, the replacement of the SIRS criteria with the quick Sepsis-related Organ Failure Assessment (qSOFA), and the complete removal of “severe sepsis” as an entity.

The new definition of sepsis is that it is “life-threatening organ dysfunction caused by a dysregulated host response to infection.”

 Septic shock is “a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to increase mortality.”

In essence this means that septic shock is sepsis plus the following, despite adequate fluid resuscitation:

  • Vasopressors required to maintain a MAP > 65 mmHg
  • Serum lactate > 2 mmol/l

The qSOFA score is a bedside prompt designed to identify patients with suspected infection who are at greater risk for a poor outcome outside of the intensive care unit. It uses the following three criteria:

  • Hypotension (SBP < 100 mmHg)
  • Tachypnoea (RR > 22)
  • Altered mental status (GCS < 15)

The presence of 2 or more of the qSOFA criteria near the onset of infection is associated with greater risk of death or a prolonged intensive care unit stay.


The Surviving Sepsis Bundles

The Surviving Sepsis Bundles represent the key elements of care regarding the diagnosis and treatment of patients with sepsis and septic shock. They allow a set of relatively complex guidelines to be translated into simple and meaningful elements of care that, when implemented as a group, have an effect on outcomes beyond implementing the individual elements alone.

One of the main changes in the latest version of the guidelines is that static fluid measurements (i.e. central venous pressure monitoring) are no longer recommended, as they carry limited value for measuring fluid responsiveness. The current update recommends the use of dynamic variables instead, such as passive leg raise, pulse pressure variation, and stroke volume variation.

The current Surviving Sepsis Bundles are as follows:

3-hour bundle (to be completed within 3 hours of time of presentation):

  1. Measure lactate level
  2. Obtain blood cultures prior to administration of antibiotics
  3. Administer broad spectrum antibiotics
  4. Administer 30 ml/kg crystalloid for hypotension or lactate ≥ 4mmol/L

6-hour bundle (to be completed within 6 hours of time of presentation):

  1. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥ 65mmHg
  2. In the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, re-assess volume status and tissue perfusion and document findings according to table 1 (see below)
  3. Re-measure lactate if initial lactate elevated.



Think Sepsis

It is clearly very important to remain up-to-date with guideline changes but perhaps the most important thing to remember is that sepsis is a killer and that we should all “think sepsis” in any patient that presents with a suspected infection. It should be at the forefront of all our minds during day-to-day practice.

Sepsis can present without fever and with non-specific symptoms and signs. A high index of suspicion should be maintained in the very young and very old, immunocompromised and pregnant patients, patients with a history of recent surgery or trauma, and those that have indwelling catheters and devices.

When a diagnosis of sepsis is suspected act quickly and without delay. Refer to departmental and regional guidance, start fluids and antibiotics early, and if unsure whether your patient could have sepsis seek senior help immediately. Sepsis awareness saves lives.


Thank you to the joint editorial team of for this article.

Header image used on licence from Shutterstock

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