What is Sepsis?
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection 1, 2.
Core Definition
This modern definition (established in 2016) represents a critical shift from older terminology. Sepsis is not simply an infection with inflammation—it specifically requires:
- An infection (confirmed or suspected)
- Organ dysfunction remote from the infection site
- Dysregulated host response (not just normal immune activation)
The key distinguishing feature is that sepsis involves organ damage from the body's own malfunctioning immune response to infection, not just from the infection itself 2, 3.
Pathophysiology
Sepsis occurs when the body's recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) triggers:
- Overzealous inflammation causing acute organ dysfunction
- Simultaneous profound anti-inflammatory response that increases susceptibility to secondary infections
- Activation of multiple pathways including cytokine storms, coagulation cascade dysfunction, cellular apoptosis, and mitochondrial dysfunction 2, 3
This dual immune dysregulation—both hyperinflammation and immunosuppression occurring together—explains why sepsis is so deadly and difficult to treat 3.
Clinical Recognition
Use the NEWS2 score to stratify risk in acute hospital, mental health, and ambulance settings 1. The NEWS2 incorporates six physiological parameters:
- Respiration rate
- Oxygen saturation (with adjustment for hypercapnic patients)
- Supplemental oxygen requirement
- Systolic blood pressure
- Pulse rate
- Level of consciousness
- Temperature
Risk categories based on NEWS2 scores:
- 0: Very low risk
- 1-4: Low risk
- 5-6: Moderate risk
- ≥7: High risk
Septic Shock
Septic shock is a subset of sepsis with profound circulatory and cellular-metabolic abnormalities that substantially increases mortality 2. Operationally defined as:
- Requiring vasopressor therapy to maintain mean arterial pressure >65 mmHg AND
- Serum lactate >2 mmol/L despite adequate fluid resuscitation
Common Pitfalls
Do not confuse sepsis with simple bloodstream infection 4. The presence of bacteria in blood (bacteremia) without organ dysfunction is not sepsis. What separates sepsis from routine infections is the presence of organ dysfunction from the dysregulated host response 4.
Sepsis is frequently under-documented and under-coded in medical records 5. Explicit documentation of "sepsis" in the chart dramatically increases coding accuracy (OR 19.58), while pneumonia as the infection source paradoxically reduces sepsis recognition despite being the most common cause 6, 5.
Most Common Sources
The most frequent infection sources leading to sepsis are 6:
- Respiratory (pneumonia is the single most common cause)
- Gastrointestinal
- Genitourinary
- Skin and soft tissue