What is Sepsis?
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is one of the leading causes of morbidity and mortality worldwide, responsible for an estimated 11 million deaths annually — about 20% of all global deaths. Early recognition and treatment are critical, as each hour of delay in antibiotic administration increases mortality by approximately 4–8%.
The understanding of sepsis has evolved significantly over the decades. The original 1991 consensus definition (Sepsis-1) was based on the Systemic Inflammatory Response Syndrome (SIRS), while the 2016 Sepsis-3 definitions shifted focus to organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, with qSOFA as a bedside screening tool.
SIRS Criteria (Traditional Definition)
SIRS is defined by the presence of two or more of the following criteria:
| Criterion | Threshold |
|---|---|
| Temperature | > 38°C (100.4°F) or < 36°C (96.8°F) |
| Heart Rate | > 90 bpm |
| Respiratory Rate | > 20 breaths/min (or PaCO2 < 32 mmHg) |
| White Blood Cell Count | > 12,000/µL or < 4,000/µL (or >10% bands) |
Under the traditional definition: Sepsis = SIRS (≥2 criteria) + confirmed or suspected infection. Severe Sepsis = Sepsis + organ dysfunction. Septic Shock = Severe sepsis + hypotension refractory to fluid resuscitation.
While SIRS remains useful for screening, it has been criticized for being overly sensitive and nonspecific — up to 50% of hospitalized patients may meet SIRS criteria from non-infectious causes such as surgery, trauma, or pancreatitis.
Sepsis-3 Definition & qSOFA
In 2016, the Third International Consensus Definitions (Sepsis-3) redefined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. The key change was replacing SIRS with organ dysfunction (SOFA score increase ≥2) as the defining feature.
Score range: 0–3 | Positive: ≥ 2 points
| qSOFA Criterion | Points |
|---|---|
| Respiratory rate ≥ 22 breaths/min | 1 |
| Systolic blood pressure ≤ 100 mmHg | 1 |
| Altered mental status (GCS < 15) | 1 |
qSOFA ≥ 2 in the setting of suspected infection should prompt clinicians to investigate for organ dysfunction (full SOFA score), consider ICU-level care, and initiate appropriate management. qSOFA is intended as a bedside screening tool, not a replacement for clinical judgment.
SIRS vs. Sepsis-3 Comparison
Septic Shock
Septic shock is a subset of sepsis with particularly severe circulatory, cellular, and metabolic abnormalities. Under Sepsis-3, septic shock is defined by:
- Sepsis (infection + organ dysfunction)
- Persisting hypotension requiring vasopressors to maintain MAP ≥ 65 mmHg despite adequate fluid resuscitation
- Serum lactate > 2 mmol/L
Patients with septic shock have a hospital mortality rate exceeding 40%, making it one of the most lethal conditions in critical care medicine.
Surviving Sepsis Campaign
The Surviving Sepsis Campaign (SSC) publishes evidence-based guidelines for the management of sepsis and septic shock. Key recommendations from the latest guidelines include:
Hour-1 Bundle
- Measure lactate level; remeasure if initial lactate is > 2 mmol/L
- Obtain blood cultures before administering antibiotics
- Administer broad-spectrum antibiotics within 1 hour of recognition
- Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L
- Apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mmHg
Additional Management
- Source control: Identify and treat the source of infection (drainage, debridement, device removal)
- De-escalate antibiotics based on culture results
- Dynamic measures of fluid responsiveness over static measures
- Norepinephrine as first-line vasopressor
- Low-dose corticosteroids (hydrocortisone 200 mg/day) for refractory septic shock
- Target glucose < 180 mg/dL; lung-protective ventilation if ARDS develops
Worked Example
A 65-year-old patient presents with suspected pneumonia. Vitals: Temp 38.6°C, HR 110, RR 24, SBP 95, WBC 15.2, Lactate 3.1 mmol/L, confused (GCS 14).
With suspected infection and both SIRS (4/4) and qSOFA (3/3) positive, this patient has sepsis by both definitions. With lactate > 2 mmol/L and hypotension, evaluation for septic shock is warranted pending assessment of vasopressor need.
Frequently Asked Questions
Should I use SIRS or qSOFA?
Both tools have their place. SIRS is more sensitive (catches more patients) but less specific. qSOFA is more specific for poor outcomes but may miss early sepsis. Many institutions use SIRS for initial screening and qSOFA for risk stratification. The Sepsis-3 guidelines recommend qSOFA as a bedside prompt to investigate for organ dysfunction rather than as a diagnostic criterion.
Can you have sepsis without meeting SIRS criteria?
Yes. The Sepsis-3 definition is based on organ dysfunction (SOFA), not SIRS. Studies show that approximately 12% of ICU patients with sepsis do not meet SIRS criteria. This was one of the key motivations for updating the definition.
What is the SOFA score?
The Sequential Organ Failure Assessment (SOFA) score assesses six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal, neurological) on a 0–4 scale each. A SOFA increase of ≥2 from baseline in the setting of infection defines sepsis. qSOFA is a simplified bedside version using only three easily assessable variables.
Is lactate always elevated in sepsis?
No. Lactate is a marker of tissue hypoperfusion and anaerobic metabolism, but not all sepsis patients have elevated lactate. However, an elevated lactate (>2 mmol/L) is associated with worse outcomes and is a criterion for septic shock. Serial lactate clearance (>10% decrease over 2 hours) is used to monitor resuscitation adequacy.
How does age affect sepsis presentation?
Elderly patients may present atypically — hypothermia instead of fever, altered mental status as the primary sign, and blunted tachycardic response due to medications (e.g., beta-blockers). Neonates and immunocompromised patients may also have atypical presentations. A high index of suspicion is essential in these populations.