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Published on: February 20, 2021
Sepsis and septic shock
Richard S Hotchkiss1, Lyle L Moldawer2, Steven M Opal3
1Department of Anesthesiology, Washington University of St. Louis, St. Louis, Missouri, USA.
Abstract:
For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
Insights
Sepsis is now viewed as a complex immune response causing organ injury, with declining mortality but long-term risks. Advances in treatment are slow due to its complexity and lack of diagnostic biomarkers.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Immunology
Background:
- Sepsis was historically defined by infection and signs like fever and elevated leukocytes.
- Current understanding views sepsis as a systemic inflammatory and immune response to infection, leading to organ injury.
- Septic shock involves hypotension and hyperlactatemia, carrying high in-hospital mortality rates.
Purpose of the Study:
- To review the evolving definition and understanding of sepsis.
- To discuss the shift in sepsis from an acute to a chronic critical illness.
- To highlight challenges in sepsis management and outcome prediction.
Main Methods:
- Literature review and synthesis of current understanding of sepsis.
- Analysis of historical and contemporary definitions of sepsis and septic shock.
- Discussion of clinical outcomes, including mortality and long-term sequelae.
Main Results:
- Sepsis is increasingly recognized as a dysregulated immune response with declining mortality rates (15-25%).
- Septic shock mortality remains high (30-50%), requiring vasopressors.
- Survivors face long-term risks, including mortality, cognitive, and functional deficits.
Conclusions:
- Sepsis is a complex chronic critical illness with prolonged inflammation and immune suppression.
- Despite improved recognition and care, immunomodulatory treatments have shown limited success.
- No definitive sepsis biomarker exists, and outcome prediction remains challenging.
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