What is Sepsis
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, clinically identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with in-hospital mortality exceeding 10%. 1
Core Definition Framework
The current Sepsis-3 definition emphasizes organ dysfunction rather than inflammation alone, representing a fundamental shift from previous definitions that focused on systemic inflammatory response syndrome (SIRS) criteria. 1
The key diagnostic criterion is an increase in SOFA score of ≥2 points, which quantifies organ dysfunction across six systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological. 1
The outdated concepts of SIRS and "severe sepsis" are no longer used in clinical practice, as they lacked specificity and failed to capture the true pathophysiology of the syndrome. 1
Pathophysiology
Sepsis begins when pathogen-associated molecular patterns (PAMPs) from microorganisms are recognized by the host immune system, triggering inflammatory signaling pathways that lead to production of pro-inflammatory cytokines. 2
The condition involves a dysregulated inflammatory response that can progress to multi-organ failure through endothelial dysfunction, coagulopathy, and microcirculatory dysfunction leading to tissue hypoperfusion. 3, 2
More than 90% of sepsis cases are caused by bacteria (Gram-negative and Gram-positive organisms occurring with approximately equal frequency), with fungi, particularly Candida species, responsible for a significant minority of cases. 1
After the initial inflammatory phase, sepsis often leads to an immunosuppressed state characterized by mobilization of immunosuppressive cells and production of anti-inflammatory cytokines, increasing susceptibility to secondary infections. 2, 4
Clinical Identification
For rapid identification outside the ICU, the quick SOFA (qSOFA) criteria consist of three clinical variables: respiratory rate ≥22 breaths/min, altered mental status (Glasgow Coma Scale score ≤13), and systolic blood pressure ≤100 mmHg. 1
Presence of at least 2 qSOFA criteria suggests higher risk of poor outcomes typical of sepsis and should prompt further evaluation with full SOFA scoring. 1
Early recognition is crucial for improving outcomes, as timely initiation of appropriate antimicrobial therapy and supportive care significantly impacts patient survival. 1, 5
Septic Shock: The Most Severe Form
Septic shock is a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with hospital mortality exceeding 40%. 3, 1
Clinically identified by the requirement for vasopressor therapy to maintain mean arterial pressure ≥65 mmHg AND serum lactate level >2 mmol/L (>18 mg/dL) in the absence of hypovolemia. 3, 1
The lactate elevation reflects altered cellular metabolism and tissue hypoperfusion despite potentially normal macrocirculatory parameters. 3, 2
Special Population Considerations
Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection, making diagnosis more challenging. 3, 1
Immunocompromised patients (including those with HIV) have increased susceptibility to sepsis due to pre-existing immune system dysfunction and exhaustion. 3, 1
Patient factors including age, comorbidities, genetic characteristics, and co-existing illnesses significantly affect the clinical course and outcomes of sepsis. 1
Common Diagnostic Pitfalls
Failing to recognize that normal blood pressure does not exclude sepsis—organ dysfunction can occur before hemodynamic collapse. 1
Over-reliance on SIRS criteria (fever, tachycardia, tachypnea, leukocytosis), which are no longer part of the sepsis definition due to poor specificity. 1
Delaying diagnosis while waiting for positive blood cultures, as prior antibiotic therapy may lead to negative cultures despite ongoing infection. 1
Confusing colonization with infection when interpreting microbiological findings, particularly with organisms of low virulence. 1