What is the definition of sepsis?

Definition of Sepsis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized by an acute increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with in-hospital mortality exceeding 10%. 1, 2

Current Sepsis-3 Definition Framework

The modern definition represents a fundamental shift from previous inflammation-focused criteria to an organ dysfunction-centered approach:

• Sepsis requires two components: (1) documented or suspected infection AND (2) acute organ dysfunction manifested by a SOFA score increase of ≥2 points from baseline 1, 2
• The previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in current clinical practice 2
• This definition was established in 2016 by the Society of Critical Care Medicine and European Society of Intensive Care Medicine, replacing earlier inflammation-based criteria 1

Septic Shock Definition

Septic shock is a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities that substantially increase mortality risk. 1, 3

Clinical identification requires both of the following despite adequate fluid resuscitation:

• Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg 3, 4
• Serum lactate level >2 mmol/L (>18 mg/dL) in the absence of hypovolemia 3, 4
• Hospital mortality exceeds 40% when both criteria are present 4

Quick SOFA (qSOFA) for Rapid Screening

For patients outside the ICU with suspected infection, qSOFA provides rapid bedside assessment using three clinical variables:

• Respiratory rate ≥22 breaths/minute 2
• Altered mental status (Glasgow Coma Scale score ≤13) 2
• Systolic blood pressure ≤100 mmHg 2

Presence of ≥2 qSOFA criteria suggests higher risk of poor outcomes and should prompt consideration of sepsis, though it does not define sepsis itself 2, 5. The predictive validity of qSOFA outside the ICU (AUROC 0.81) exceeds that of SOFA or SIRS criteria in non-ICU settings 5.

Risk Stratification Using NEWS2

The updated 2024 NICE guidance incorporates the National Early Warning Score 2 (NEWS2) for stratifying risk of severe illness or death from sepsis in acute hospital settings:

• NEWS2 aggregates six physiological parameters: respiratory rate, oxygen saturation, supplemental oxygen requirement, systolic blood pressure, pulse rate, consciousness level, and temperature 1
• Risk categories guide urgency of intervention: 0 (very low), 1-4 (low), 5-6 (moderate), and ≥7 (high risk) 1
• This scoring system helps determine the time window for antibiotic administration based on patient risk level 1

Evolution from Previous Definitions

Critical distinction: The pre-2016 definition focused on SIRS criteria (temperature abnormalities, tachycardia, tachypnea, and white blood cell count changes), which proved insufficiently specific for identifying patients at risk of death from infection 1, 2. The Sepsis-3 definition recognizes that:

• Sepsis represents a dysregulated host response—not simply inflammation 1, 6
• Organ dysfunction, not inflammatory markers, determines clinical significance 6, 7
• The pathophysiology involves both excessive "resistance" responses causing immunopathology and inappropriate "disease tolerance" leading to immunoparalysis 7

Pathophysiological Basis

The definition reflects understanding that sepsis involves:

• Dysregulated inflammatory response with both pro-inflammatory and anti-inflammatory pathways activated simultaneously 8, 9
• Microcirculatory dysfunction leading to tissue hypoperfusion despite adequate macrocirculation 3
• Cellular metabolic abnormalities including mitochondrial dysfunction and altered cellular metabolism 3, 6
• Early pathogen engagement with endothelial cells and platelets driving the excessive host response 9

Clinical Implications

Early recognition is crucial for improving outcomes, as sepsis represents a medical emergency comparable to acute myocardial infarction or stroke 1, 2. The definition emphasizes that:

• Over 90% of sepsis cases are caused by bacteria (Gram-negative and Gram-positive with equal frequency), with fungi responsible for a significant minority 2
• Patient factors including age, comorbidities, and immune status significantly affect disease course 2
• Elderly patients may present with attenuated inflammatory responses despite severe infection 2, 4
• Immunocompromised patients have increased susceptibility due to pre-existing immune dysfunction 2, 4