Sepsis is a life-threatening medical condition defined as organ dysfunction resulting from a host’s dysregulated response to an infection. When the immune system overreacts to a pathogen, the response can injure the body’s own tissues and organs, leading to potentially fatal effects. Recognizing this process quickly is paramount, as early identification and treatment significantly increase the probability of survival. Diagnostic criteria standardize how clinicians identify this syndrome and facilitate the rapid initiation of life-saving interventions. These criteria focus on detecting signs of infection combined with evidence of new or worsening organ damage.
The Evolution of Diagnostic Definitions
The understanding of sepsis and its diagnosis has undergone several significant revisions since the first consensus definitions were established in 1991. These initial definitions, known as Sepsis-1, relied heavily on the presence of Systemic Inflammatory Response Syndrome (SIRS) criteria. Sepsis was diagnosed if a patient had a suspected infection and met at least two of the four SIRS criteria, which included abnormal temperature, heart rate, respiratory rate, or white blood cell count. This framework also established “severe sepsis” and “septic shock” as a progression of the disease.
A limitation of the SIRS-based approach was its lack of specificity; the criteria could be met by conditions other than infection, such as trauma, burns, or pancreatitis. This resulted in high sensitivity but low specificity, flagging many patients who did not have true sepsis. The Sepsis-2 definitions in 2001 expanded the list of signs but did not fundamentally change the SIRS core, failing to resolve the diagnostic ambiguity.
The current standard, established in 2016, is the Third International Consensus Definitions for Sepsis and Septic Shock, widely known as Sepsis-3. This update officially eliminated the terms “severe sepsis” and the SIRS criteria from the definition of sepsis. The Sepsis-3 task force shifted the focus from a purely inflammatory response to the presence of life-threatening organ dysfunction. This new approach provides a more accurate reflection of the underlying disease process.
Identifying Sepsis Using Current Clinical Criteria
The Sepsis-3 definition operationalizes organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score. Sepsis is clinically identified when a patient with a suspected infection exhibits an acute increase in their total SOFA score of two points or more from their baseline. This score evaluates the function of six different organ systems:
- Respiration
- Coagulation
- Liver
- Cardiovascular
- Central nervous system
- Renal
The SOFA score provides a systematic way to quantify the degree of injury, which may be subtle or “occult” in the early stages.
For patients not known to have pre-existing organ damage, the baseline SOFA score is often assumed to be zero. An increase of two points or more is associated with an approximate in-hospital mortality rate greater than 10%. The SOFA scoring system uses specific laboratory and clinical data, such as the ratio of oxygen in the blood to the concentration of inspired oxygen (PaO2/FiO2), platelet count, bilirubin levels, and creatinine levels. It also incorporates the Glasgow Coma Scale for mental status and the need for vasopressors to assess cardiovascular function.
Quick SOFA (qSOFA) Screening
For rapid, bedside screening outside of the Intensive Care Unit (ICU), the quick SOFA (qSOFA) criteria were developed as a simpler tool. The qSOFA score is a screening tool used to identify patients with suspected infection who are at a higher risk of poor outcomes, but it is not a diagnostic criterion for sepsis itself. A patient is considered qSOFA-positive if they meet at least two of three specific clinical criteria:
- Respiratory rate of 22 breaths per minute or greater
- Systolic blood pressure of 100 mm Hg or less
- Altered mental status
The presence of two or more of these signs signals the need for urgent investigation and the potential initiation of sepsis protocols.
Laboratory Markers for Confirmation
While clinical scoring systems like SOFA and qSOFA provide a framework for identifying organ dysfunction, laboratory tests are essential for confirming infection, assessing metabolic derangement, and monitoring organ injury. The serum lactate level is a key measurement in the initial assessment. Elevated lactate, typically greater than 2 mmol/L, indicates tissue hypoperfusion and anaerobic metabolism, signifying that organs are not receiving enough oxygen.
Blood cultures remain the definitive method for identifying the specific pathogen—such as bacteria, fungi, or viruses—causing the infection. Cultures are drawn from two or more sites and are crucial for guiding appropriate antibiotic therapy, though results can take 24 to 72 hours. Two supplementary inflammatory biomarkers are used to help confirm infection or guide treatment decisions. C-Reactive Protein (CRP) is a protein produced by the liver in response to inflammation, and its elevated levels are a general indicator of an inflammatory process.
Procalcitonin (PCT) is a marker that is more specific for bacterial infections than CRP. PCT levels help clinicians distinguish between bacterial and non-bacterial causes of inflammation and are sometimes used to monitor treatment response or determine when antibiotic therapy can be safely stopped. Standard laboratory tests that make up the SOFA score track specific organ damage, such as elevated creatinine for acute kidney injury and increased bilirubin for liver dysfunction. A complete blood count may also show an abnormally high or low white blood cell count, reflecting the body’s response to the infection.
Recognizing Septic Shock
Septic shock is the most severe manifestation of sepsis, representing a profound state of circulatory, cellular, and metabolic failure that carries a significantly higher risk of mortality, often exceeding 40%. The diagnosis is based on two specific clinical criteria that must persist despite adequate fluid resuscitation, which involves giving intravenous fluids to restore blood volume and improve circulation.
The first criterion is persistent hypotension requiring the use of vasopressors—medications that constrict blood vessels to raise blood pressure. These medications must be necessary to maintain a Mean Arterial Pressure (MAP) of 65 mm Hg or greater. The second defining criterion is a persistently elevated serum lactate level, specifically greater than 2 mmol/L. This combination of circulatory failure and metabolic derangement confirms a diagnosis of septic shock and necessitates immediate, aggressive life support.