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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2], Parth Vikram Singh, MBBS[3] Jason Le, B.S.[4]
Synonyms and keywords: sepsis syndrome; septic shock; septicemia
Sepsis — Overview
Definition
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Under the Sepsis-3 framework, infection-associated organ dysfunction is operationalized as an acute increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score attributable to infection. In a general population with suspected infection, a SOFA increase of ≥2 is associated with an in-hospital mortality of approximately 10%.[1]
Septic shock is a subset of sepsis characterized by profound circulatory, cellular, and metabolic abnormalities and substantially higher mortality. It is identified by vasopressor requirement to maintain a mean arterial pressure ≥65 mm Hg together with a serum lactate >2 mmol/L despite adequate fluid resuscitation; hospital mortality exceeds 40%.[2]
The modern definition therefore frames sepsis as infection-associated organ dysfunction rather than infection plus systemic inflammation. The terms "severe sepsis" and "septicemia" are no longer part of the current Sepsis-3 framework.[3]
Why it matters
Sepsis and septic shock are time-critical medical emergencies. Early recognition should prompt urgent evaluation and treatment, with antimicrobial therapy, assessment and support of perfusion, and identification and control of the infectious source forming the core of early management.[4][5]
The global burden is substantial. The GBD 2021 analysis estimated approximately 166 million sepsis cases and 21.4 million sepsis-related deaths worldwide in 2021. Sepsis-related deaths represented approximately 31.5% of all global deaths in 2021, compared with 19.7% in the 2017 analysis. The 2020–2021 increase reflected a COVID-19-associated surge that reversed declines in sepsis burden observed since 1990.[6][7]
The earlier GBD 2017 analysis estimated 48.9 million incident cases and 11.0 million sepsis-related deaths annually.[8]
In the United States, sepsis is involved in more than one third of in-hospital deaths and represents a major hospitalization burden. Incidence and mortality are strongly age-dependent, with high rates in infancy, lower rates during mid-adulthood, and a marked increase with older age.[9]
Recognition and initial management
Recognition of sepsis is clinical and should not depend on a single screening score. qSOFA comprises respiratory rate ≥22/min, altered mentation (Glasgow Coma Scale <15), and systolic blood pressure ≤100 mm Hg. It may identify patients at increased risk of poor outcome but has insufficient sensitivity to serve as the sole screening tool.[10]
The 2021 Surviving Sepsis Campaign guideline issued a strong recommendation against using qSOFA as a single screening tool, and the 2026 guideline issued a strong recommendation, based on moderate-certainty evidence, in favor of using NEWS, NEWS2, MEWS, or SIRS over qSOFA as a single screening tool.[11][12]
In pooled meta-analyses, qSOFA has substantially lower sensitivity for identifying sepsis (approximately 0.42–0.46) than early warning scores such as NEWS (approximately 0.71–0.73), although qSOFA has higher specificity.[13][14]
SOFA requires laboratory and clinical data and provides the organ-dysfunction framework used in the Sepsis-3 definition. Detailed scoring, diagnostic testing, and screening algorithms are addressed in the dedicated Classification, Screening, and Laboratory findings microchapters.
Early management includes obtaining appropriate cultures and lactate, administering antimicrobials promptly, supporting perfusion when hypoperfusion is present, and pursuing source control when indicated. Detailed fluid strategies, antimicrobial selection and dosing, vasopressor therapy, and procedural management belong in Medical therapy and Surgery/procedural therapy.[15]
Prognosis and recovery
Mortality increases with severity, from approximately 10% with the organ dysfunction threshold defining sepsis to more than 40% with septic shock.[16]
Recovery does not necessarily end at hospital discharge. Sepsis survivors may develop persistent functional limitations, cognitive impairment, psychological sequelae, recurrent infection, cardiovascular and renal events, and recurrent hospitalization. Readmission risk is substantial, with approximately 40% readmission within 90 days reported in the cited literature.[17][18]
Long-term mortality remains elevated after discharge. Post-sepsis follow-up, rehabilitation, and secondary prevention are addressed in the Natural history, complications, and prognosis and Secondary prevention microchapters.[19]
How to use this topic
This Overview provides a high-level clinical orientation. Detailed content is organized into dedicated microchapters:
- Historical perspective — evolution of the sepsis concept and major changes in definitions and management paradigms.
- Classification — current sepsis and septic shock categories and operational criteria.
- Pathophysiology — mechanisms of dysregulated host response, organ injury, endothelial dysfunction, and coagulopathy.
- Causes / Etiology — infectious sources and causative pathogens.
- Differentiating sepsis from other diseases — important mimics and alternative shock states.
- Epidemiology and demographics — population-level incidence, mortality, and demographic distribution.
- Risk factors — individual predisposition and relevant exposures.
- Screening — early recognition tools and institutional screening approaches.
- History and symptoms — presenting symptoms and source-localizing history.
- Physical examination — bedside findings and assessment of perfusion.
- Laboratory findings — laboratory assessment, SOFA components, lactate, and related testing.
- Other diagnostic studies — additional diagnostic modalities when indicated.
- Medical therapy — antimicrobial, resuscitative, vasopressor, and other medical management.
- Surgery/procedural therapy — source-control procedures and related interventions.
- Natural history, complications, and prognosis — acute complications and short- and long-term outcomes.
- Secondary prevention — post-sepsis follow-up, rehabilitation, and prevention of recurrent morbidity.
References
- ↑ Singer M, Deutschman CS, Seymour CW; et al. (2016). "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 801–810. doi:10.1001/jama.2016.0287.
- ↑ Shankar-Hari M, Phillips GS, Levy ML; et al. (2016). "Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 775–787. doi:10.1001/jama.2016.0289.
- ↑ Meyer NJ, Prescott HC. (2024). "Sepsis and Septic Shock". The New England Journal of Medicine. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213.
- ↑ Evans L, Rhodes A, Alhazzani W; et al. (2021). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021". Critical Care Medicine. 49 (11): e1063–e1143. doi:10.1097/CCM.0000000000005337.
- ↑ Prescott HC, Antonelli M, Alhazzani W; et al. (2026). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026". Critical Care Medicine. 54 (4): 725–812. doi:10.1097/CCM.0000000000007075.
- ↑ GBD 2021 Global Sepsis Collaborators. (2025). "Global, Regional, and National Sepsis Incidence and Mortality, 1990-2021: A Systematic Analysis". The Lancet Global Health. doi:10.1016/S2214-109X(25)00356-0.
- ↑ Rudd KE, Johnson SC, Agesa KM; et al. (2020). "Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study". The Lancet. 395 (10219): 200–211. doi:10.1016/S0140-6736(19)32989-7.
- ↑ Rudd KE, Johnson SC, Agesa KM; et al. (2020). "Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study". The Lancet. 395 (10219): 200–211. doi:10.1016/S0140-6736(19)32989-7.
- ↑ Meyer NJ, Prescott HC. (2024). "Sepsis and Septic Shock". The New England Journal of Medicine. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213.
- ↑ Singer M, Deutschman CS, Seymour CW; et al. (2016). "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 801–810. doi:10.1001/jama.2016.0287.
- ↑ Evans L, Rhodes A, Alhazzani W; et al. (2021). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021". Critical Care Medicine. 49 (11): e1063–e1143. doi:10.1097/CCM.0000000000005337.
- ↑ Prescott HC, Antonelli M, Alhazzani W; et al. (2026). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026". Critical Care Medicine. 54 (4): 725–812. doi:10.1097/CCM.0000000000007075.
- ↑ Wang C, Xu R, Zeng Y, Zhao Y, Hu X. (2022). "A Comparison of qSOFA, SIRS and NEWS in Predicting the Accuracy of Mortality in Patients With Suspected Sepsis: A Meta-Analysis". PLOS ONE. 17 (4): e0266755. doi:10.1371/journal.pone.0266755.
- ↑ Qiu X, Lei YP, Zhou RX. (2023). "SIRS, SOFA, qSOFA, and NEWS in the Diagnosis of Sepsis and Prediction of Adverse Outcomes: A Systematic Review and Meta-Analysis". Expert Review of Anti-Infective Therapy. 21 (8): 891–900. doi:10.1080/14787210.2023.2237192.
- ↑ Prescott HC, Antonelli M, Alhazzani W; et al. (2026). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026". Critical Care Medicine. 54 (4): 725–812. doi:10.1097/CCM.0000000000007075.
- ↑ Singer M, Deutschman CS, Seymour CW; et al. (2016). "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 801–810. doi:10.1001/jama.2016.0287.
- ↑ Prescott HC, Angus DC. (2018). "Enhancing Recovery From Sepsis: A Review". JAMA. 319 (1): 62–75. doi:10.1001/jama.2017.17687.
- ↑ Meyer NJ, Prescott HC. (2024). "Sepsis and Septic Shock". The New England Journal of Medicine. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213.
- ↑ Rahmel T, Schmitz S, Nowak H; et al. (2020). "Long-Term Mortality and Outcome in Hospital Survivors of Septic Shock, Sepsis, and Severe Infections: The Importance of Aftercare". PLOS ONE. 15 (2): e0228952. doi:10.1371/journal.pone.0228952.
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