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, operationally identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. 1

Current Definition Framework (Sepsis-3,2016)

The modern definition represents a fundamental shift from previous inflammation-focused criteria:

• Sepsis is life-threatening organ dysfunction resulting from a dysregulated host response to infection 2, 1
• Organ dysfunction is clinically identified by an increase in SOFA score ≥2 points, which correlates with in-hospital mortality >10% 1
• The previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in the current definition framework 1

Key Conceptual Change

The Sepsis-3 definition emphasizes organ dysfunction rather than inflammatory response alone, moving away from the older SIRS-based approach that focused on temperature, heart rate, respiratory rate, and white blood cell count 1, 3

Quick SOFA (qSOFA) for Rapid Identification

For rapid bedside assessment outside the ICU, qSOFA consists of three clinical variables 1:

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

Presence of at least 2 of these criteria suggests higher risk of poor outcomes and should prompt consideration of sepsis 1

Septic Shock Definition

Septic shock is a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with substantially higher mortality 2, 4, 5

Operational Criteria for Septic Shock

Both of the following must be present despite adequate fluid resuscitation 4, 5:

• Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg
• Serum lactate level >2 mmol/L (>18 mg/dL)

Common Pitfalls in Identifying Septic Shock

• Failing to recognize that patients on vasopressors may still have perfusion abnormalities despite normalized blood pressure 4, 5
• Delaying vasopressor initiation while continuing excessive fluid administration 4, 5
• Not measuring lactate levels, which are essential for diagnosis 4
• Confusing septic shock with other forms of distributive shock 4

Evolution from Previous Definitions

The pre-2016 definitions focused heavily on inflammation using SIRS criteria, which required at least two of 2, 1:

• Temperature >38°C or <36°C
• Heart rate >90 beats/minute
• Respiratory rate >20 breaths/minute or PaCO2 <32 mmHg
• White blood cell count >12,000/mm³ or <4,000/mm³, or >10% immature (band) forms

This approach has been abandoned because it overemphasized inflammation and failed to capture the critical element of organ dysfunction 1, 3

Pathophysiological Basis

Sepsis involves 2, 6, 7:

• Recognition of pathogen-associated molecular patterns (PAMPs) by host immune receptors including Toll-like receptors
• A dysregulated inflammatory response that can be both hyperinflammatory and immunosuppressive
• Microcirculatory dysfunction leading to tissue hypoperfusion
• Mitochondrial dysfunction and altered cellular metabolism
• Activation of coagulation cascades and increased apoptosis

More than 90% of sepsis cases are caused by bacteria (Gram-negative and Gram-positive with approximately equal frequency), with fungi accounting for a significant minority 1

Clinical Implications

• Early recognition is crucial for improving outcomes, as the condition represents a spectrum of severity with potential for rapid deterioration 1, 6
• Patient factors including age, comorbidities, and immune status significantly affect the clinical course 1
• Immunocompromised patients have increased susceptibility due to pre-existing immune dysfunction 1
• Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection 1