What is sepsis?

What is Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. 1, 2, 3

Core Definition and Diagnostic Criteria

Sepsis represents a clinical syndrome where the body's response to infection becomes harmful rather than protective, leading to organ damage and potential death. 1 The current Sepsis-3 definition framework emphasizes that sepsis requires both an infection AND organ dysfunction—not just infection alone. 2, 3

Operational Identification

• Organ dysfunction is clinically identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points, which correlates with in-hospital mortality exceeding 10%. 2, 3
• The presence of organ dysfunction distinguishes sepsis from simple infection or bloodstream infections. 3, 4
• Previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in the current definition framework. 2

Quick Recognition Outside the ICU

For rapid bedside identification, the quick SOFA (qSOFA) criteria consist of three clinical variables: 2

• Respiratory rate ≥22 breaths/minute
• Altered mental status (Glasgow Coma Scale score ≤13)
• Systolic blood pressure ≤100 mmHg

Presence of at least 2 of these criteria suggests higher risk of poor outcomes typical of sepsis. 2

Septic Shock: The Most Severe Form

Septic shock represents a subset of sepsis with particularly profound abnormalities and dramatically higher mortality (>40%). 3, 5 It is clinically identified by: 2, 5

• Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg AND
• Serum lactate level >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation

These patients experience profound circulatory, cellular, and metabolic abnormalities including vasodilation, increased vascular permeability, microcirculatory dysfunction, and altered cellular metabolism. 5

Epidemiology and Impact

• Globally, sepsis affects 48.9 million people annually with 11 million sepsis-related deaths. 3
• In the United States, there are >1.7 million adult cases per year with >15% mortality. 3
• Worldwide, approximately 30 million people are hospitalized with sepsis each year and up to six million die. 1

Pathophysiology: The Dysregulated Response

The hallmark of sepsis is a dysregulated immune response—not simply an excessive inflammatory response. 2, 6 This involves: 3, 7

• Recognition of pathogen-associated molecular patterns (PAMPs) by the host immune system
• Both excessive activation of inflammatory pathways (causing immunopathology and tissue damage) and inappropriate immune suppression (causing immunoparalysis)
• Impaired cellular function including mitochondrial dysfunction and altered cell death mechanisms
• Coagulation cascade activation, leading to microvascular thrombosis and impaired tissue perfusion

Causative Organisms

• More than 90% of sepsis cases are caused by bacteria, with Gram-negative and Gram-positive organisms occurring with approximately equal frequency. 2, 3
• Fungi, particularly Candida species, are responsible for a significant minority of cases. 2

Risk Stratification Using NEWS2

The updated 2024 NICE guidance recommends calculating NEWS2 (National Early Warning Score 2) scores to determine an adult's risk of severe illness or death from sepsis in acute hospital, mental health, and ambulance settings. 1 This score incorporates six physiological measurements: 1

• Respiration rate
• Oxygen saturation (with two scales depending on hypercapnic respiratory failure risk)
• Air or oxygen requirement
• Systolic blood pressure
• Pulse rate
• Consciousness level (Alert vs CVPU)
• Temperature

The aggregate score determines risk categories: 0 (very low), 1-4 (low), 5-6 (moderate), with higher scores indicating greater urgency for intervention. 1

Key Risk Factors

Major risk factors for developing sepsis include: 3

• Age extremes (very young and elderly)
• Immune compromise
• Chronic diseases
• Male sex and Black race
• Immunocompromised states (e.g., HIV-positive patients have increased susceptibility due to pre-existing immune system activation and exhaustion) 2

Clinical Implications

• Early recognition is crucial for improving outcomes, as failing to recognize clinical deterioration promptly can be life-threatening. 1, 2
• Patient factors including age and comorbidities significantly affect the course and outcomes of sepsis. 2, 3
• Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection. 2
• The inflammatory response depends on both the causative pathogen and host factors (genetic characteristics and co-existing illnesses). 2