Data from Alex Keen - Curated by EPG Health - Last updated 20 March 2018

Sepsis is a potentially life-threatening complication, caused by an infection that is allowed to spread rapidly throughout the body, triggering systemic inflammation that damages tissue and affects blood flow. This interference can lead to hypotension, creating hypoxic conditions within tissues and organs, eventually leading to septic shock, multi-organ failure and death if left untreated.

At nearly 30 million annual cases and 6 million deaths globally, sepsis is one of the world’s biggest killers, however, as it can be caused by many different pathogens and has varying presentations, the diagnosis is often missed. This is especially apparent in developing countries where the burden is highest, making it difficult to compile accurate statistics. In the developed world the incidence of sepsis is increasing, thought to be due to an aging population and an increasing number of surgical interventions. With sepsis hospitalisation rates being higher than stroke and heart attack combined, and almost half of the ICU bed days in the UK used for severe sepsis, there is a real need for timely diagnosis and treatment to reduce complications, decrease ICU length of stay and improve prognosis.

The Surviving Sepsis Campaign was launched in 2002 with the aim of reducing mortality from sepsis by 25% by 2009. Two clinical care bundles were created containing a number of evidence-based interventions to be completed within either 3 or 6 hours of sepsis recognition, depending on patient need. Although these bundles are simplistic and seemingly easy to implement, worldwide compliance is weak with only around a quarter of hospitals successfully applying these guidelines. To help address the concerns, a new bundle was developed from the Surviving Sepsis Campaign that incorporated both diagnostic and therapeutic tools. This became The Sepsis Six, a collection of steps designed to ensure rapid diagnosis and treatment, with the goal to improve outcomes and reduce the burden of this time-sensitive condition.

The Sepsis Six


Deliver O2 to target 94–98 % SpO2 or 88–92 % in COPD

Improving oxygen saturation reduced tissue hypoxia, reducing damage


Take blood cultures

Two sets of blood cultures should be taken to identify the pathogens causing the infection


Give IV antibiotics

Broad-spectrum IV antibiotics should be administered to target the most likely causes of the infection


Start IV fluid resuscitation

This prevents hypotension and improves cardiac output, improving tissue perfusion


Measure serum lactate

Elevated lactate levels indicate cellular stress and the severity of sepsis


Monitor urine output

The kidneys are often the first organ to show signs of stress in sepsis, therefore monitoring urine output is a good indicator of sepsis progression

Grey, therapeutic; White, diagnostic.

The guideline is designed to be easy to implement and follow in order to overcome the commonly reported difficulties of introducing a new protocol or routine to a hospital, such as instigating long-term behavioural changes among staff to encourage uptake. If these 6 steps are completed within an hour of sepsis recognition, as the guideline states, mortality rates have been shown to drop by up to 50%.

To help improve compliance to The Sepsis Six, the mnemonic BUFALO was created:

  • Blood cultures
  • Urine output measurement, monitored hourly
  • Fluid resuscitation
  • Antibiotics IV
  • Lactate measurement
  • Oxygen

BUFALO carries all the same steps as The Sepsis Six, however, they are arranged into a memorable mnemonic designed to improve uptake and compliance in hospitals, ultimately ensuring septic patients receive the best and most appropriate care in the shortest possible time.

Although BUFALO and The Sepsis Six appear to be simple implementations, in practice they require a coordinated response from a large multi-disciplinary team of healthcare professionals in order to perform all steps within the hour. In a busy A&E department where staff are spread thin and have a number of other, potentially more pressing commitments, it is a difficult protocol to introduce and sustain. Critics have also argued that The Sepsis Six does nothing to promote the early identification of sepsis, with this protocol being frequently used after septic shock has set in. If guidance to help identify sepsis earlier was incorporated into The Sepsis Six, sepsis could be treated before it is allowed to progress, leading to better outcomes for everyone involved.   

This highlights the need for a greater push to evolve and implement these protocols; provide sufficient training and guidance to frontline staff; address conflicts between commitments to other patients and regularly review and update these practices.

Resources & further reading

ISICEM 2018 will be held in Brussels, Belgium from 20–23 March 2018. View resources from previous ISICEM events here.

Click here to read a recent summary of exciting research into the role of gut bacteria in sepsis.

The Sepsis Trust ED/AMU Sepsis Screening & Action Tool

NICE sepsis guidelines

NICE sepsis algorithms

Surviving Sepsis Campaign

BMJ Best Practice – Sepsis in adults 

Daniels R, et al. The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J. 2011 Jun;28(6):507–12.

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