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. According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), organ dysfunction can be represented by an increase in the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score of 2 points or more 1.

Current Definition Framework (Sepsis-3)

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

Septic Shock Definition

• Septic shock is defined as a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with a greater risk of mortality 1
• Clinically identified by:
  • Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg AND
  • Serum lactate level >2 mmol/L (>18 mg/dL) in the absence of hypovolemia 1, 2
• This combination is associated with hospital mortality rates greater than 40% 2

Quick SOFA (qSOFA) Criteria

For rapid identification of patients at risk of sepsis outside the ICU setting (emergency department, general wards):

• 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 typical of sepsis 2

Evolution of Sepsis Definitions

• Previous definitions (pre-2016) focused heavily on inflammation and used SIRS criteria 1, 3
• SIRS was defined as at least two of:
  • 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 1
• The Sepsis-3 task force eliminated SIRS from the definition due to inadequate specificity and sensitivity 3, 2

Clinical Implications

• Early recognition is crucial for improving outcomes 1
• The pathophysiology involves a dysregulated inflammatory response that can lead to multi-organ failure 4
• Sepsis represents a spectrum of severity with differential responses at local, regional, and systemic levels 1
• Patient factors including age and comorbidities significantly affect the course of sepsis 1

Special Considerations

• Immunocompromised patients (e.g., HIV-positive) have increased susceptibility to sepsis due to pre-existing immune system activation and exhaustion 1
• Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection 1
• The inflammatory response depends on both the causative pathogen and host factors (genetic characteristics and co-existing illnesses) 1

The updated Sepsis-3 definitions provide greater consistency for epidemiologic studies and clinical trials while facilitating earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis 2.