Sepsis in adults

Last reviewed: 4 Nov 2023

Last updated: 26 Jul 2023

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 within 6-12 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.

Definition

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection.[1] The definition of sepsis was updated in 2016 following publication of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).[1] 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 widely-accepted 2016 consensus definitions marked a shift away from the previous systemic inflammatory response syndrome (SIRS) definition and the first 1991 international consensus definition, which described severe sepsis as sepsis associated with organ dysfunction, hypoperfusion, or hypotension; and septic shock as sepsis with hypotension despite adequate fluid replacement.[2]

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.[1] 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).[1]

Septic shock indicates profound circulatory, cellular, and metabolic deterioration, and is associated with a greater risk of mortality than with sepsis alone.[1]

History and exam

Key diagnostic factors

high (>101°F [>38°C]) or low (<96.8°F [<36°C]) temperature
tachycardia
tachypnea
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
cyanosis

More key diagnostic factors

Other diagnostic factors

purpura fulminans
jaundice
ileus

Other diagnostic factors

Risk factors

age >65 years
immunocompromise
indwelling intravenous lines or urinary catheters
recent surgery or other invasive procedures
hemodialysis
diabetes mellitus
intravenous drug use
alcohol use disorder
breached skin integrity
pregnancy
urban residence
lung disease
male sex
non-white ancestry
winter season

More risk factors

Diagnostic investigations

1st investigations to order

blood culture
lactate levels
CBC with differential
blood urea nitrogen (BUN) and serum electrolytes
serum creatinine
liver function tests
coagulation studies (INR, activated PTT)
serum glucose
CRP
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
ECG

More 1st investigations to order

Investigations to consider

lumbar puncture
echocardiogram (transthoracic or transesophageal)
ultrasound scan
CT chest or abdomen
serum procalcitonin

More investigations to consider

Treatment algorithm

ACUTE

presumed or confirmed sepsis

Contributors

Authors

Andre C. Kalil, MD, MPH, FACP, FIDSA, FCCM

Professor

Department of Internal Medicine

Division of Infectious Diseases

University of Nebraska Medical Center

Omaha

Disclosures

ACK declares that he has no competing interests.

Kelly Cawcutt, MD, MS, FACP, FIDSA, FCCM

Associate Professor

Department of Internal Medicine

Division of Pulmonary, Critical Care, Sleep & Allergy

University of Nebraska Medical Center

Omaha

Disclosures

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 payment from BD. KC has received honoraria and travel expenses from NAPA. KC has received payment for book proposal review from Elsevier.

Acknowledgements

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.

Disclosures

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.

Peer reviewers

Steven M. Opal, MD, FIDSA

Professor of Medicine

Infectious Disease Division

Rhode Island Hospital

Alpert Medical School of Brown University

Providence

Disclosures

SMO declares that he has no competing interests.

Laura Evans, MD, MSc, FCCP, FCCM

Associate Professor

NYU School of Medicine

Medical Director of Critical Care

Bellevue Hospital Center

New York

Disclosures

LE serves as the guidelines co-chair and on the steering committee of the Surviving Sepsis Campaign.

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Guidelines
- Surviving sepsis campaign guidelines for management of sepsis and septic shock - 2021
- Sepsis: recognition, diagnosis and early management
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Diagnostic lumbar puncture in adults: animated demonstration
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Sepsis in adults

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

presumed or confirmed sepsis

Contributors

Authors

Andre C. Kalil, MD, MPH, FACP, FIDSA, FCCM

Disclosures

Kelly Cawcutt, MD, MS, FACP, FIDSA, FCCM

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Steven M. Opal, MD, FIDSA

Disclosures

Laura Evans, MD, MSc, FCCP, FCCM

Disclosures

Differentials

Guidelines

Patient leaflets

Calculators

Videos

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice