Sepsis can progress rapidly to multiorgan failure and shock, and is often fatal. Survival is dependent on a high index of suspicion of sepsis, early recognition, and timely intervention.
Findings are generally nonspecific and secondary to primary infection. They include malaise, leukocytosis, tachypnea, tachycardia, and altered mental status.
Patients with evidence of sepsis, including signs of organ dysfunction, require immediate hospital assessment.
Empiric broad-spectrum antibiotic therapy (based on the most probable pathogens and site of infection) should be administered as soon as possible, and preferably within the first hour if the patient is progressing to shock.
Blood cultures, as well as cultures of all potentially infected body fluids, should be obtained 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 >101°F (38.3°C) or <96.8°F (36.0°C); tachycardia >90 bpm; tachypnea >20 breaths/minute or PaCO₂ <32 mmHg; hyperglycemia (blood glucose >140 mg/dL [>7.7 mmol/L]) in the absence of diabetes mellitus; acutely altered mental status; leukocytosis (WBC count >12,000/microliter); leukopenia (WBC count <4000/microliter); 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.
History and exam
Key diagnostic factors
- high (>101°F [>38°C]) or low (<96.8°F [<36°C]) temperature
- acutely altered mental status
- poor capillary refill, mottling of the skin, or ashen appearance
- signs associated with specific source of infection
- low oxygen saturation
- arterial hypotension
- decreased urine output
Other diagnostic factors
- purpura fulminans
- underlying malignancy
- age >65 years
- diabetes mellitus
- recent surgery or other invasive procedures
- breached skin integrity
- indwelling intravenous or urinary catheters
- intravenous drug use
- urban residence
- lung disease
- male sex
- non-white ancestry
- winter season
1st investigations to order
- CBC with differential
- BUN and serum electrolytes
- serum creatinine
- liver function tests
- coagulation studies (INR, activated PTT)
- serum glucose
- lactate levels
- blood culture
- other cultures (e.g., of sputum, stool, urine, wounds, catheters, prosthetic implants, epidural sites, pleural or peritoneal fluid)
- arterial blood gas (ABG) or venous blood gas (VBG)
- chest x-ray
Investigations to consider
- lumbar puncture
- echocardiogram (transthoracic or transesophageal)
- ultrasound scan
- CT chest or abdomen
- serum procalcitonin
presumed or confirmed sepsis
Andre C. Kalil, MD, MPH, FACP, FIDSA, FCCM
Department of Internal Medicine
Division of Infectious Diseases
University of Nebraska Medical Center
ACK declares that he has no competing interests. ACK is an author of references cited in this topic.
Kelly Cawcutt, MD
Department of Internal Medicine
Division of Pulmonary, Critical Care, Sleep & Allergy
University of Nebraska Medical Center
KC has received payment for medical writing from IDSA and CloroxPro. KC has received honoraria for creation of educational materials from the Society for Healthcare Epidemiology of America (SHEA) and BD. KC has received honoraria and travel expenses from NAPA. KC has received payment for book proposal review from Elsevier.
Professor Andre Kalil and Dr Kelly Cawcutt would like to gratefully acknowledge Dr Ron Daniels, Dr Matt Inada-Kim, Dr Aamir Saifuddin, Dr Tim Nutbeam, Dr Edward Berry, Dr Lewys Richmond, and Dr Paul Kempen, previous contributors to this topic.
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 Organization, and NHS England on sepsis. Each of these positions demands that he express opinion on strategies around the recognition and management of sepsis. 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. 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. TN is a clinical adviser to the UK Sepsis Trust. EB, LR, and PK declare that they have no competing interests.
Steven M. Opal, MD, FIDSA
Professor of Medicine
Infectious Disease Division
Rhode Island Hospital
Alpert Medical School of Brown University
SMO declares that he has no competing interests.
Laura Evans, MD, MSc, FCCP, FCCM
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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