Severe sepsis is a major cause of morbidity and mortality, claiming between 36 000 and 64 000 lives annually in the UK, with a mortality rate of 35%. International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles. In 2010, the Campaign published results from its improvement programme showing that, although an absolute mortality reduction of 5.4% was seen over a 2 year period in line with increasing compliance with the Bundles, reliability was not achieved and Bundle compliance reached only 31%. This article explores current challenges in sepsis care and opportunities for further improvements. Basic care tasks [microbiological sampling and antibiotic delivery within 1 h, fluid resuscitation, and risk stratification using serum lactate (or alternative)] are likely to benefit patients most, yet are unreliably performed. Barriers include lack of awareness and robust process, the lack of supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex life-saving tasks (such as early goal-directed therapy) demands greater awareness, faster recognition and initiation of basic care, and more effective collaboration between clinicians and nurses on the front line, in critical care and in specialist support services, such as microbiology and infectious diseases. Organizations such as Survive Sepsis, the Surviving Sepsis Campaign and the Global Sepsis Alliance are working to raise awareness and promote further improvement initiatives. Future developments will focus on sepsis biomarkers and microarray techniques to rapidly screen for pathogens, risk stratification using genetic profiling, and the development of novel therapeutic agents targeting immunomodulation.


Sepsis is a common condition with a major impact on healthcare resources and expenditure. The incidence of severe sepsis (sepsis-induced organ dysfunction) in the European Union has been estimated at 90.4 cases per 100 000 population, as opposed to 58 per 100 000 for breast cancer.1 The documented incidence of sepsis worldwide is 1.8 million cases annually, but this figure reflects low rates of recognition and diagnosis. Recent estimates give an incidence of sepsis requiring intensive care admission of 0.25–0.38 per 1000 population, suggesting ∼2 million admissions to intensive care units (ICUs) alone.2,3 In 1992, it was estimated that 1400 people worldwide were dying each day from severe sepsis,4 although the true figure is likely to be much higher and rising. A more recent US study estimated 3.0 cases to occur per 1000 population per year,5 or ∼20 million cases per year. With a mortality of 35%, this would mean ∼20 000 deaths per day worldwide and 64 000 deaths annually in the UK.
Data from the UK Intensive Care National Audit and Research Centre (ICNARC) covering the last 6 months of 2005 showed that 8300 patients died from severe sepsis on ICUs.6 Between 65% and 70% of eligible ICUs in the UK contribute data to ICNARC, and only ∼70% of patients with severe sepsis are treated on an ICU.7 This gives an estimated 36 800 deaths annually in the UK (Figure 1). The mortality rate from severe sepsis has been estimated in a number of studies as between 28% and 50%.5,8,9 More recently, the Sepsis Occurrence in Acutely ill Patients (SOAP) study in Europe observed an overall hospital mortality of 36%.10 Data from the Surviving Sepsis Campaign (SSC) showed a mortality of 34.8%11 among 15 022 patients, and ICNARC data show that 39.8% of those admitted to critical care in England and Wales die in hospital. There are few disease processes with such a high mortality. An admission with severe sepsis places the patient at a level of risk ∼6–10-fold greater than if he were admitted with an acute myocardial infarction and 4–5 times greater than if he had suffered an acute stroke.
Figure 1.
Chart showing relative mortality figures in 1year for the UK for common conditions. Sources: sepsis, ICNARC data 2006. For all others: for England and Wales, Office for National Statistics 2008; for Scotland, General Register Office Registrar General Annual Report 2008; and for Northern Ireland, Statistics and Research Agency Registrar General Annual Report 2008.
There has been considerable debate around treatment guidelines, particularly those relating to invasive management and critical care. The most widely discussed guidelines are those from the SSC. This article aims to set the background and to offer discussion on the most important issues facing clinicians in the UK: those of early recognition and immediate, basic management.


In 2002, critical care experts agreed that concerted action was needed to reduce the mortality from severe sepsis. The SSC was developed as a collaboration between the European Society of Critical Care Medicine, the International Sepsis Forum and the Society of Critical Care Medicine. A desire to reduce the mortality from sepsis by 25% over a 5 year period became known as the Barcelona Declaration.12 In March 2004, the SSC guidelines for the management of severe sepsis and septic shock were published—these were subsequently updated in 2008.13,14 Care Bundles were created in collaboration with the Institute for Healthcare Improvement. The first (the Resuscitation Bundle) comprised a set of tasks to complete within the first 6 h following the identification of sepsis (Figure 2).
Figure 2.
The Surviving Sepsis Campaign Resuscitation Bundle. Source: www.survivingsepsis.org.
In 2010, the SSC published results from its improvement programme, which concluded in December 2008.11 Data were reported for 15 022 patients from 165 sites across 30 countries and showed that 71.5% of patients presented with septic shock. Compliance with the Resuscitation Bundle rose over a 2 year period from 10.9% to 31.3%, with mortality reducing over the same period from 37.0% to 30.8% (P < 0.001). Adjusted mortality was reduced by 0.8% for each quarter that a site was in the SSC, with an absolute mortality reduction of 5.4% over 2 years [95% confidence interval (CI) 2.5%–8.4%]. The delivery of early antibiotics and sampling for culture prior to antibiotics were each found to be independently associated with survival, as was the maintenance of tight glycaemic control over the first 24 h [odds ratios (OR) for mortality 0.86, 0.76 and 0.67, respectively; upper 95% CI limits <1 .0="" class="Apple-converted-space" span="">