Definition of Sepsis
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, operationally identified by an acute increase in the Sequential Organ Failure Assessment (SOFA) score of 2 or more points. 1, 2
Core Diagnostic Components
Sepsis requires two essential elements to be present simultaneously: 2
- Documented or suspected infection (the trigger)
- Acute organ dysfunction represented by an increase in SOFA score ≥2 points, which correlates with in-hospital mortality >10% 2
Clinical Identification Using SOFA Score
The SOFA score increase of ≥2 points represents clinically significant organ dysfunction and distinguishes sepsis from uncomplicated infection. 1, 2 This threshold was chosen because it is associated with in-hospital mortality exceeding 10%, marking the transition from infection to life-threatening illness. 2
Quick SOFA (qSOFA) for Rapid Bedside Assessment
For rapid identification outside the ICU, qSOFA consists of three clinical variables: 2
- Respiratory rate ≥22 breaths/minute
- Altered mental status (Glasgow Coma Scale score ≤13)
- Systolic blood pressure ≤100 mmHg
The presence of at least 2 of these criteria suggests higher risk of poor outcomes typical of sepsis and should prompt urgent evaluation. 2
Septic Shock: The Most Severe Subset
Septic shock is a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with a greater risk of mortality. 1, 2, 3 It is clinically identified by: 1, 2, 3
- Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg
- Serum lactate level >2 mmol/L (>18 mg/dL)
- Persistence despite adequate fluid resuscitation
Hospital mortality exceeds 40% when both vasopressor requirement and elevated lactate are present. 3
Evolution from Previous Definitions
The current definition framework (Sepsis-3, published in 2016) represents a fundamental shift from earlier concepts. 1, 2 The previous SIRS-based criteria are no longer used, as they focused heavily on inflammation rather than organ dysfunction. 2 The old SIRS criteria included at least two of: temperature >38°C or <36°C, heart rate >90 beats/minute, respiratory rate >20 breaths/minute, and white blood cell count >12,000/mm³ or <4,000/mm³. 1, 2
The term "severe sepsis" has been eliminated from the current definition framework, as all sepsis by definition involves organ dysfunction and is therefore life-threatening. 2
Risk Stratification Using NEWS2
For determining urgency of treatment in acute hospital settings, calculate NEWS2 scores based on six physiological measurements: respiratory rate, oxygen saturation, supplemental oxygen requirement, systolic blood pressure, pulse rate, level of consciousness, and temperature. 1 The NEWS2 score interpretation for risk of severe illness or death from sepsis is: 1
- 0 = very low risk
- 1-4 = low risk
- 5-6 = moderate risk
- ≥7 = high risk
Key Clinical Implications
Early recognition is crucial for improving outcomes, as sepsis represents a medical emergency similar to stroke or myocardial infarction. 2 The pathophysiology involves a dysregulated inflammatory response that can rapidly progress to multi-organ failure. 2
Common Pitfalls to Avoid:
- In elderly patients, altered mental status may be the primary or only presenting sign—do not attribute confusion to dementia without investigating for underlying infection. 4
- Underestimating severity due to less dramatic vital sign abnormalities despite significant organ dysfunction, particularly in elderly or immunocompromised patients. 4
- Failing to recognize that patients receiving vasopressors may still have perfusion abnormalities despite normalized blood pressure. 3
Special Population Considerations
Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection due to immune senescence. 4 Any change in mental status with suspected infection warrants immediate evaluation in this population. 4
Immunocompromised patients (including those with HIV) have increased susceptibility to sepsis due to pre-existing immune system activation and exhaustion. 2