For many years corticosteroids have been recommended as an adjunctive treatment in patients with septic shock who are refractory to fluids and vasopressor agents. Now a large randomised controlled trial, published in January 2018, has cast doubt on the benefits of this approach. In the trial of 3,658 patients with septic shock, there was no significant difference in 28-day or 90-day mortality between those who received a continuous infusion of hydrocortisone (200 mg per day for 7 days) compared with those who received placebo (90-day mortality of 27.9% in the hydrocortisone group vs 28.8% for placebo). Those who received hydrocortisone did experience faster resolution of shock (median 3 vs 4 days) and were less likely to need a blood transfusion (37.0% vs 41.7%) but there were no significant differences in length of ICU stay or need for renal replacement therapy.See Management: approach See Management: treatment algorithm
Where available, measurement of serum procalcitonin should be considered in all patients with sepsis to guide antibiotic therapy. Among patients with acute respiratory infections (including those resulting in sepsis), procalcitonin guided therapy was associated with a 2 day reduction in the antibiotic course, a 27% reduction in antibiotic related side-effects, and a 10% reduction in 30 day mortality rate.See Diagnosis: investigations
Findings are generally non-specific and secondary to primary infection. They include malaise, leukocytosis, tachypnoea, and pulse >90 bpm.
Sepsis can progress rapidly to multi-organ failure and shock, and is often fatal. Survival is dependent on a high index of suspicion of sepsis, early recognition and immediate intervention.
Patients with evidence of sepsis, including signs of organ dysfunction, require immediate hospital assessment.
Empirical broad-spectrum antibiotic therapy (based on the most probable pathogens) should be administered as soon as possible, and always within the first hour following recognition.
Blood cultures, as well as cultures of all wounds or other potentially infected body fluids, should be performed as indicated by symptoms and the risk profile of the patient, ideally before the initiation of antimicrobial treatment.
Any source of infection should be controlled as a matter of urgency, preferably within 6 hours following recognition.
Evidence of hypoperfusion or shock should be identified and treated with immediate intravenous fluid challenges, if present. Shock that fails to respond to fluid challenges necessitates urgent critical care referral for consideration of vasopressors and/or inotropes.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection.  The definition of sepsis was updated in 2016 following publication of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). 
The 2016 consensus definitions also recommend that the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria and 'quick' (q)SOFA criteria be used to identify sepsis, in place of the currently used systemic inflammatory response syndrome (SIRS) criteria, which were the basis for the previous definition of sepsis.   SOFA is an ICU-based mortality score and qSOFA is a rapid, shortened version of SOFA designed for use outside the ICU. The SOFA scores are not in themselves clinical predictors of sepsis, and they rely on clinical suspicion for the scores to be assessed. Furthermore, qSOFA has not been prospectively validated, and its place in clinical practice has not been fully established. Although the SIRS criteria are no longer recommended and have limitations, they are well established after many years of use.  At present it is unclear which clinical score will best guide sepsis care; therefore, the SIRS criteria remain the current standard for identifying sepsis and are likely to remain relevant in medical care, at least in the short term.
SIRS is a multi-system response that can result from infection (localised or general), as well as from non-infectious causes (e.g., trauma, burns, or pancreatitis).      It is defined by the presence of 2 or more criteria from the following: temperature >38.3°C (101°F) or <36.0°C (96.8°F); tachycardia >90 bpm; tachypnoea >20 breaths/minute or PaCO2 <4.3 kPa (32 mmHg); hyperglycaemia (blood glucose >7.7 mmol/L [>140 mg/dL]) in the absence of diabetes mellitus; acutely altered mental status; leukocytosis (WBC count >12×10^9/L [12,000/microlitre]); leukopenia (WBC count <4×10^9/L [4000/microlitre]); or a normal WBC count with >10% immature forms. 
When using the SIRS criteria, sepsis is the presence of SIRS (i.e., 2 or more SIRS criteria) resulting specifically from an infection.
In the first international consensus definitions, which date from 1991, severe sepsis was defined as sepsis associated with organ dysfunction, hypoperfusion, or hypotension; septic shock was defined as sepsis with hypotension despite adequate fluid replacement.  These definitions remain clinically established in many clinical settings.
However, the 2016 third international consensus (Sepsis-3) definitions state that the term 'severe sepsis' should be made redundant in light of the revisions to the definition of sepsis.  Septic shock has also been redefined as a subset of sepsis, in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. 
In 2016, the National Institute for Health and Care Excellence (NICE) published guidance on the recognition, diagnosis, and early management of sepsis, which highlighted that the Sepsis-3 international consensus definitions of sepsis have limited use in the early identification of people at risk of sepsis.  The NICE guidelines propose a move away from using the SIRS criteria, and do not immediately support the use of the SOFA/qSOFA criteria. Instead NICE proposes a risk stratification approach to categorise patients into 3 groups according to their risk of severe illness or death from sepsis: high risk; moderate to high risk; or low risk. The risk stratification is based on the patient’s: history (e.g., altered mental state; urine output; impaired immunity; or recent trauma, surgery, or invasive procedure), appearance (e.g., signs of potential infection; mottled or ashen appearance; cyanosis of skin, lips, or tongue; or non-blanching rash of skin), and clinical evaluation (e.g., temperature, heart rate, respiratory rate, blood pressure, level of consciousness, and oxygen saturation).
United Kingdom Sepsis Trust
Global Sepsis Alliance
Consultant in Critical Care and Anaesthesia
Heart of England NHS Foundation Trust
RD has received payment for consultancy on sepsis from Kimal Plc, manufacturers of vascular access devices, from the Northumbria Partnership, a patient safety collaborative, and, where annual leave or other income was compromised in fulfilling his charity duties, from the UK Sepsis Trust. RD has received sponsorship to attend and speak at one meeting from Abbott Diagnostics. He is CEO of the UK Sepsis Trust and Global Sepsis Alliance, and advises HM Government, the World Health Organisation and NHS England on sepsis. Each of these positions demands that he express opinion on strategies around the recognition and management of sepsis.
Consultant in Emergency Medicine
University of Plymouth
Devon Air Ambulance Trust
TN is a clinical advisor to the UK Sepsis Trust.
Specialty Registrar in Emergency Medicine
EC declares that he has no competing interests.
Dr Ron Daniels, Dr Tim Nutbeam, and Dr Edward Berry would like to gratefully acknowledge Dr Lewys Richmond and Dr Paul Kempen, the previous contributors to this monograph. LR and PK declare that they have no competing interests.
Professor of Medicine
Infectious Disease Division
Rhode Island Hospital
Alpert Medical School of Brown University
SMO declares that he has no competing interests.
NYU School of Medicine
Medical Director of Critical Care
Bellevue Hospital Center
LE serves as the guidelines co-chair and on the steering committee of the Surviving Sepsis Campaign.
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