Definition of Sepsis
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. 1
Current Definition (2016)
The Society of Critical Care Medicine and the European Society of Intensive Care Medicine established the current definition of sepsis in 2016 (Sepsis-3), which represents a significant update from previous definitions:
- Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection
- Organ dysfunction: Identified as an acute increase in SOFA score ≥2 points
- Septic shock: A subset of sepsis characterized by:
- Circulatory, cellular, and metabolic abnormalities
- Need for vasopressors to maintain mean arterial pressure ≥65 mmHg
- Serum lactate >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation
- Hospital mortality exceeding 40% 1
Evolution of Sepsis Definitions
2001 Definition (Sepsis-2)
- Infection plus two or more of the following criteria:
- Heart rate >90 bpm
- Respiratory rate ≥20/min or PaCO₂ <32 mmHg
- Temperature <36°C or >38°C
- White blood cell count <4×10⁶ or >12×10⁶ g/L or >10% immature forms 1
2016 Definition (Sepsis-3)
- Moved away from the systemic inflammatory response syndrome (SIRS) criteria
- Focused on organ dysfunction as the defining characteristic
- Introduced the quick SOFA (qSOFA) score for rapid bedside assessment 1, 2
Clinical Assessment Tools
SOFA Score
- Evaluates six organ systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological
- Maximum score of 24 points
- Increase of ≥2 points indicates organ dysfunction associated with sepsis 1
qSOFA Score
- Bedside tool to identify patients at risk of sepsis outside ICU
- Three parameters:
- Altered mental status
- Systolic blood pressure ≤100 mmHg
- Respiratory rate >22/min
- Score ≥2 indicates high risk of poor outcomes 1, 3
National Early Warning Score 2 (NEWS2)
- Evaluates six physiological parameters
- Scores range from 0 (very low risk) to ≥7 (high risk) 1
Clinical Manifestations of Sepsis
Signs of hypoperfusion that indicate sepsis include:
- Altered mental status
- Hypotension (systolic blood pressure <90 mmHg or mean arterial pressure <70 mmHg)
- Decreased urine output
- Elevated lactate
- Delayed capillary refill
- Mottled skin 1
Pathophysiological Basis
Sepsis involves an abnormal immune response to infection that damages the body's own tissues and organs:
- Dysregulated host response
- Organ dysfunction
- Metabolic derangements including hyperglycemia and dysfunctional lipid metabolism
- Mitochondrial dysfunction leading to cellular energy failure 1, 4
Clinical Implications
- Early recognition is crucial for improving outcomes
- Delayed recognition leads to increased mortality
- Each additional failing organ system increases mortality risk 1, 5
Common Pitfalls in Sepsis Diagnosis
Overreliance on SIRS criteria: The 2016 definition moved away from SIRS criteria as they lack specificity and can be present in many non-septic conditions 2
Delayed recognition: Failure to recognize sepsis early significantly increases mortality. Use structured assessment tools like qSOFA and NEWS2 to identify at-risk patients 1, 5
Underestimating organ dysfunction: The presence of organ dysfunction is now central to the definition of sepsis. Careful assessment of all organ systems is essential 1
Missing sepsis in trauma patients: Sepsis is a major cause of death following traumatic injury and requires early prediction based on qSOFA 3
The current definition represents a significant advancement in our understanding of sepsis, moving from a focus on inflammation to emphasizing the life-threatening nature of organ dysfunction caused by the dysregulated host response to infection 1, 2.