There has been long-running debate over whether prolonged infusion of intravenous antibiotics, including beta-lactams, is more effective than standard infusion in improving outcomes in sepsis. Now a meta-analysis has found that patients with sepsis who received their intravenous anti-pseudomonal beta-lactam infusion over at least 3 hours were 30% less likely to die than those who received beta-lactam either as a bolus or as a short-term infusion over 1 hour or less (RR 0.7, 95% CI 0.56 to 0.87). The meta-analysis included 22 randomised controlled trials totalling 1876 patients. The authors concluded that the weight of evidence is high for the benefits of prolonged infusion in patients with sepsis. An accompanying editorial called for the prolonged infusion of beta-lactams over at least 3 hours to become standard practice in intensive care unit settings, even though most administration guides still recommend an infusion over 15 to 60 minutes. See Management: approach See Management: treatment algorithm
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 (RCT), 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 intensive care unit stay or need for renal replacement therapy.
However, in another RCT of patients with septic shock, when hydrocortisone was administered in combination with fludrocortisone, the 90- and 180-day all-cause-mortality rates were significantly lower. See Management: approach See Management: treatment algorithm
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).  This recommended that organ dysfunction should be defined using the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria or the 'quick' (q)SOFA criteria.
The 2016 consensus definitions marked a shift away from the previous systemic inflammatory response syndrome (SIRS) definition, which classified sepsis as two or more of the following in the context of infection: 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 >12×10⁹/L [12,000/microlitre]); leukopenia (WBC count <4×10⁹/L [4000/microlitre]); or a normal WBC count with >10% immature forms. 
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. 
However, the 2016 Third International Consensus Group (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 there is co-existence of: persistent hypotension requiring vasopressors to maintain mean arterial pressure ≥65 mmHg; and serum lactate >2 mmol/L (>18 mg/dL). 
Septic shock indicates profound circulatory, cellular, and metabolic deterioration, and is associated with a greater risk of mortality than with sepsis alone. 
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 Acute Physician & Sepsis Lead
Department of Acute Medicine
Royal Hampshire County Hospital
Hampshire Hospitals NHS Foundation Trust
MIK is a national clinical advisor on sepsis to NHS England and a national clinical advisor on deterioration to NHS Improvement. He was reimbursed for a slide set by Relias Learning.
Specialty Registrar in Gastroenterology and General Medicine
Maidstone and Tunbridge Wells NHS Trust
AS is the clinical fellow to the National Medical Director at NHS Improvement. AS has been sponsored on two occasions by Dr Falk Pharma UK to attend specialist gastroenterology conferences abroad; there was no contractual obligation to disseminate product information.
Consultant in Emergency Medicine
University of Plymouth
Devon Air Ambulance Trust
TN is a clinical adviser to the UK Sepsis Trust.
Specialty Registrar in Emergency Medicine
EC declares that he has no competing interests.
Dr Ron Daniels, Dr Matt Inada-Kimand, Dr Aamir Saifuddin, Dr Tim Nutbeam, and Dr Edward Berry would like to gratefully acknowledge Dr Lewys Richmond and Dr Paul Kempen, previous contributors to this topic. 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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