Definition of Sepsis According to Latest Guidelines
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. 1, 2
Core Definition (Sepsis-3)
The current definition represents a fundamental shift from previous inflammation-focused criteria:
- Sepsis is life-threatening organ dysfunction resulting from a dysregulated host response to infection 1
- Organ dysfunction is clinically identified by an acute increase in SOFA score ≥2 points, which correlates with in-hospital mortality >10% 2
- The previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in the current definition framework 2, 3
This definition emphasizes that sepsis is not merely infection with inflammation, but specifically involves organ dysfunction from a maladaptive host response 1, 4
Septic Shock Definition
Septic shock is a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with greater mortality risk. 1, 5
Clinical criteria for septic shock include:
- Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg AND
- Serum lactate level >2 mmol/L (>18 mg/dL) in the absence of hypovolemia 2, 5
These patients have substantially higher mortality rates than sepsis alone 1
Quick SOFA (qSOFA) for Rapid Identification
For bedside screening outside the ICU, qSOFA consists of three simple clinical variables:
- Respiratory rate ≥22 breaths/min
- Altered mental status (Glasgow Coma Scale score ≤13)
- Systolic blood pressure ≤100 mmHg 2, 6
Presence of ≥2 qSOFA criteria suggests higher risk of poor outcomes and should prompt consideration of sepsis, though it should not replace clinical judgment or be used as a definitive diagnostic criterion 2, 6, 7
Key Conceptual Changes from Previous Definitions
The Sepsis-3 definition (published 2016) eliminated the SIRS-based approach used since 1991:
- Old definition (pre-2016): Required ≥2 SIRS criteria (temperature >38°C or <36°C, heart rate >90 bpm, respiratory rate >20/min or PaCO2 <32 mmHg, WBC >12,000/mm³ or <4,000/mm³) plus infection 2, 3
- New definition: Focuses on organ dysfunction rather than inflammatory markers alone, recognizing that SIRS criteria had high sensitivity but very low specificity 2, 7
This shift reflects understanding that the inflammatory response alone does not define sepsis—rather, it is the resulting organ dysfunction that determines the syndrome 4, 8
Clinical Implications
Early recognition is crucial for improving outcomes, as sepsis requires time-sensitive interventions similar to stroke or myocardial infarction 1, 2
Important considerations:
- The pathophysiology involves both excessive "resistance" responses (causing immunopathology) and inappropriate "tolerance" responses (causing immunoparalysis) 9
- Patient factors including age, comorbidities, and immune status significantly affect sepsis presentation and course 2
- Elderly patients may present with attenuated signs despite severe infection 2
- Immunocompromised patients have increased susceptibility due to pre-existing immune dysfunction 2
Common Pitfalls to Avoid
- Do not wait for positive cultures to diagnose sepsis—the definition is clinical, based on organ dysfunction in the setting of suspected or confirmed infection 1, 2
- Do not rely solely on qSOFA for diagnosis; it is a screening tool with lower sensitivity than SIRS but higher specificity for poor outcomes 7
- Do not confuse infection or bacteremia with sepsis—sepsis specifically requires organ dysfunction, not just presence of infection 4
- Do not overlook sepsis in patients with normal vital signs who are receiving vasopressors or have subtle organ dysfunction 5