Sepsis
Basics
Description
Sepsis-3 definitions:
- Sepsis: life-threatening acute organ dysfunction caused by a dysregulated host response
- Organ dysfunction is defined as an increase in the Sequential Organ Failure Assessment (SOFA) score ≥2 points from baseline.
- Baseline SOFA score is assumed to be zero unless there is preexisting organ dysfunction.
- Septic shock: a subset of sepsis where there is underlying circulatory and cellular/metabolic abnormalities profound enough to increase mortality
- Persistent hypotension despite adequate volume resuscitation
- Clinically defined as sepsis requiring vasopressors AND a lactate level ≥2 mmol/L
- SOFA variables:
- Respiration: PaO2/FiO2 ratio
- Central nervous system: Glasgow Coma Scale (GCS) score
- Cardiovascular: mean arterial pressure (MAP), vasopressor administration with type and rate of infusion
- Renal: serum creatinine, urine output
- Liver: bilirubin
- Coagulation: platelet count
- Quick SOFA (qSOFA) is a new bedside tool used to determine patients who are likely to develop sepsis and prompt further investigation. This tool is intended for use in non-ICU patients.
- qSOFA variables:
- Respiratory rate ≥22/min
- Altered mentation
- SBP ≤100 mm Hg
- qSOFA variables:
- Sepsis-3 criteria have not yet been widely accepted and are still controversial.
- The Centers for Medicare & Medicaid Services (CMS) supports definitions of SIRS, sepsis, severe sepsis, and septic shock.
Pediatric Considerations
- Sepsis is diagnosed with suspected or proven infection in addition to meeting at least 2 SIRS criteria.
- SIRS in pediatric population requires that abnormality in temperature or WBC be present.
- Drug metabolism is reduced in children with sepsis. Monitor drug toxicity labs to prevent adverse effects.
Geriatric Considerations
Altered mental status may be presenting sign of infection.
Epidemiology
Incidence
- Is a leading global cause of mortality and critical illness
- Increasing incidence with decreasing in-hospital mortality
- 31 million cases with ~5 million deaths annually worldwide
Etiology and Pathophysiology
- Complex pathophysiology
- Multifactorial: Widespread endothelial dysfunction, complement activation, and activation of coagulation cascade lead to tissue hypoperfusion, early hemodynamic changes, and organ dysfunction.
- An imbalance between proinflammatory and anti-inflammatory mediators leads to relative immunosuppression.
- Causative organisms (most commonly bacterial)
- Gram-positive bacteria (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.
- Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp., and anaerobic bacteria
- Fungi: Candida sp.
- Causative organism not identified in 1/3 of cases
- Nosocomial infections in 50% of cases
- Common sites of infection: upper/lower respiratory tract (most common), urinary tract, vascular and indwelling catheters, skin/soft tissue, central nervous system, gastrointestinal (GI) tract, bone, joint
Risk Factors
- Extremes of age (very young or age >60 years)
- Comorbidities: COPD, cirrhosis, congestive heart failure (CHF), cancer, diabetes, and renal insufficiency/failure
- Immunosuppression, asplenia
- Primary bacteremia
- Complicated labor and delivery: premature labor and/or premature rupture of membranes, untreated maternal group B strep colonization
- Nosocomial factors: surgical site infections, vascular and indwelling catheters, mechanical ventilation
General Prevention
- Vaccination: pneumococcal vaccine in children and adults ≥65 years or immunocompromised; Haemophilus influenzae type B (infants, young children), influenza, meningococcal vaccine
- γ-Globulin for hypo- or agammaglobulinemia
- Regular hand washing, sterile technique for vascular and indwelling catheter placement
- Antibiotic prophylaxis for recommended surgical procedures
- Prompt extubation for patients on mechanical ventilation as soon as clinically appropriate.
Commonly Associated Conditions
- Immunologic: neutropenia, HIV, hypo- or agammaglobulinemia, complement deficiency, splenectomy, immunosuppressants (corticosteroids, chemotherapy, TNF-α antagonists)
- Diabetes, alcoholism, malignancy, cirrhosis, burns, multiple trauma, intravenous (IV) drug abuse, malnutrition
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Citation
Domino, Frank J., et al., editors. "Sepsis." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688489/all/Sepsis.
Sepsis. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688489/all/Sepsis. Accessed November 14, 2024.
Sepsis. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688489/all/Sepsis
Sepsis [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 November 14]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688489/all/Sepsis.
* Article titles in AMA citation format should be in sentence-case
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