Definition of Sepsis
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, as outlined in the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) published in 2016. 1
Current Definition and Diagnostic Criteria
The current definition of sepsis focuses on organ dysfunction as the critical feature, representing a significant shift from earlier definitions that emphasized inflammatory response. Key elements include:
- Organ dysfunction: Characterized by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more 1
- Dysregulated host response: The pathophysiological basis of sepsis involves an abnormal immune response to infection that damages the body's own tissues and organs 2, 1
Septic Shock Definition
Septic shock is defined as a subset of sepsis with:
- Circulatory and cellular-metabolic abnormalities profound enough to substantially increase mortality
- Requiring vasopressor therapy to maintain mean arterial pressure ≥65 mmHg
- Serum lactate level >2 mmol/L despite adequate fluid resuscitation 1, 2
Clinical Assessment Tools
NEWS2 Score
The National Early Warning Score 2 (NEWS2) is recommended for stratifying risk of severe illness or death from sepsis 2:
- NEWS2 ≥7: High risk of death
- NEWS2 5-6: Moderate risk
- NEWS2 1-4: Low risk
- NEWS2 0: Very low risk
NEWS2 evaluates six physiological parameters:
- Respiratory rate
- Oxygen saturation
- Systolic blood pressure
- Pulse rate
- Level of consciousness
- Temperature 2
Quick SOFA (qSOFA)
The qSOFA score provides a rapid bedside assessment with three clinical parameters:
A qSOFA score ≥2 indicates higher risk of poor outcomes 1
Pathophysiology of Sepsis
Sepsis involves complex pathophysiological processes:
- Immune dysregulation: Both hyperinflammatory and immunosuppressive responses 4
- Endothelial dysfunction: Early pathogen engagement with endothelial cells contributes to organ dysfunction 5
- Platelet activation: Interaction between pathogens and platelets plays a key role in the dysregulated response 5
- Coagulation abnormalities: Disruption of normal clotting mechanisms 1
- Mitochondrial dysfunction: Contributes to cellular energy failure 6
- Apoptosis: Abnormal cell death, particularly of immune cells 4
Clinical Implications
The shift from SIRS-based criteria to organ dysfunction-based criteria has important clinical implications:
- Focuses attention on identifying organ dysfunction rather than just inflammatory response
- Emphasizes the severity and life-threatening nature of the condition
- Helps clinicians prioritize patients at highest risk of mortality
- Guides appropriate resource allocation in healthcare settings 1
Common Pitfalls and Caveats
- Delayed recognition: Failure to recognize sepsis early can lead to increased mortality. Use structured assessment tools like NEWS2 and qSOFA for early identification 2, 3
- Overemphasis on biomarkers: While biomarkers like C-reactive protein, procalcitonin, and lactate may be helpful, none are routinely recommended for diagnosis in current practice 6
- Special populations: Patients with immunosuppression or advanced age may present with attenuated inflammatory responses despite severe infection 1
- Fluid management: Avoid fluid overload in patients with generalized peritonitis, as it may aggravate gut edema and increase intra-abdominal pressure 2
Management Approach Based on Risk Level
High-risk patients (qSOFA ≥2 or NEWS2 ≥7):
Moderate-risk patients (NEWS2 5-6):
Low-risk patients (NEWS2 1-4):
Remember that sepsis is distinguished from routine infections by the presence of organ dysfunction resulting from a dysregulated host response to infection 6.