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. 1, 2
Current Sepsis-3 Definition Framework
The modern definition represents a fundamental shift from previous inflammation-focused criteria to an emphasis on organ dysfunction:
Sepsis is life-threatening organ dysfunction resulting from a dysregulated host response to infection, identified by an increase in SOFA score ≥2 points, which correlates with in-hospital mortality exceeding 10%. 1, 2
The previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in the current definition framework, as these terms have been abandoned by the Society of Critical Care Medicine. 2
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
Operationally defined by two specific criteria that must both be present:
- Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg, AND 1, 3
- Serum lactate level >2 mmol/L (>18 mg/dL) in the absence of hypovolemia 1, 3
These patients have hospital mortality rates exceeding 40%. 1
Quick SOFA (qSOFA) for Rapid Screening
For rapid identification of patients at risk outside the ICU setting, qSOFA consists of three clinical variables (≥2 suggests higher risk):
- Respiratory rate ≥22 breaths/minute 2
- Altered mental status (Glasgow Coma Scale score ≤13) 2
- Systolic blood pressure ≤100 mmHg 2
Evolution from Previous Definitions
The pre-2016 definitions focused heavily on inflammation using SIRS criteria, which required at least two of the following:
- Temperature >38°C or <36°C 1, 2
- Heart rate >90 beats/minute 1, 2
- Respiratory rate >20 breaths/minute or PaCO₂ <32 mmHg 1, 2
- White blood cell count >12,000/mm³ or <4,000/mm³, or >10% immature (band) forms 1, 2
This SIRS-based approach has been replaced because it lacked specificity and failed to capture the essence of sepsis as organ dysfunction rather than merely inflammation. 2
Key Pathophysiological Concepts
Sepsis involves recognition of pathogen-associated molecular patterns (PAMPs) by the host immune system, triggering dysregulated inflammatory signaling pathways that lead to organ dysfunction. 1, 4
The syndrome represents a spectrum of severity with differential responses at local, regional, and systemic levels, involving both proinflammatory and antiinflammatory pathways, coagulation cascade activation, apoptosis, and mitochondrial dysfunction. 2, 5
More than 90% of sepsis cases are caused by bacteria (Gram-negative and Gram-positive organisms occurring with approximately equal frequency), with fungi accounting for a significant minority. 2
Critical Clinical Implications
Early recognition is crucial for improving outcomes, as appropriate management in the initial hours after sepsis develops significantly impacts survival. 1, 2
Common Pitfalls to Avoid:
- Failing to recognize organ dysfunction in patients who do not meet SIRS criteria but have SOFA score increases 2
- Delaying vasopressor initiation in septic shock while continuing excessive fluid administration 3, 6
- Not measuring lactate levels, which are essential for diagnosing septic shock according to current definitions 3
- Overlooking attenuated presentations in elderly or immunocompromised patients who may have fewer clinical signs despite severe infection 2, 6