Recommended Diagnostic Criteria for Sepsis
Sepsis should be diagnosed when there is documented or suspected infection plus life-threatening organ dysfunction, defined as an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 or more points, which is associated with in-hospital mortality greater than 10%. 1
Core Sepsis-3 Definition
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) established the current standard, defining sepsis as "life-threatening organ dysfunction caused by a dysregulated host response to infection." 2 This definition fundamentally shifted away from the inflammatory response-based approach to an organ dysfunction-based approach.
Sequential Organ Failure Assessment (SOFA) Score
The SOFA score is the gold standard for identifying sepsis-related organ dysfunction and requires assessment of six organ systems: 1
- Respiratory: PaO2/FiO2 ratio <300 or SpO2 ≤90% 1
- Cardiovascular: Hypotension (SBP <90 mmHg or MAP <70 mmHg) or vasopressor requirement 1
- Renal: Creatinine >2.0 mg/dL (176.8 μmol/L) or urine output <0.5 mL/kg/h for ≥2 hours 1
- Hepatic: Bilirubin >2 mg/dL (34.2 μmol/L) 1
- Coagulation: Platelets <100,000/μL or INR >1.5 1
- Neurological: Altered mental status or decreased Glasgow Coma Scale 1
An increase of 2 or more SOFA points from baseline indicates organ dysfunction consistent with sepsis. 3 Research validates that SOFA scores >11 have 100% sensitivity and negative predictive value for sepsis diagnosis, and demonstrate superior discriminatory ability (AUROC 0.89) compared to other scoring systems. 4
Quick SOFA (qSOFA) for Rapid Bedside Assessment
The qSOFA score serves as a rapid screening tool outside the ICU, with 2 or more of the following criteria prompting immediate concern for sepsis: 5
Critical distinction: qSOFA is designed for non-ICU settings to identify patients who may need closer monitoring or ICU transfer. 3 In ICU patients, SOFA demonstrates significantly better predictive validity (AUROC 0.74) compared to qSOFA (AUROC 0.66). 3 However, outside the ICU, qSOFA shows superior discrimination (AUROC 0.81) compared to SOFA (AUROC 0.79). 3
Septic Shock Criteria
Septic shock is diagnosed when sepsis criteria are met PLUS one of the following after adequate fluid resuscitation: 2
- Persistent hypotension (SBP <90 mmHg, MAP <65 mmHg, or >40 mmHg decrease in SBP) 2
- Lactate >4 mmol/L 2
For pregnant patients (20 weeks gestation through 3 days postpartum), the hypotension threshold is modified to SBP <85 mmHg. 2
Alternative Diagnostic Parameters (When SOFA Cannot Be Calculated)
When SOFA scoring is not feasible, the Surviving Sepsis Campaign criteria require documented or suspected infection PLUS any of the following categories: 2, 6
General Variables:
- Fever >38.3°C or hypothermia <36°C 2, 6
- Heart rate >90/min or >2 SD above normal for age 2, 6
- Tachypnea 2, 6
- Altered mental status 2, 6
- Significant edema or positive fluid balance (>20 mL/kg over 24 hours) 2, 6
- Hyperglycemia (>140 mg/dL or 7.7 mmol/L) without diabetes 2, 6
Inflammatory Variables:
- Leukocytosis (WBC >12,000/μL) or leukopenia (WBC <4,000/μL) 2, 6
- Normal WBC with >10% immature forms (bandemia) 2, 6
- C-reactive protein or procalcitonin >2 SD above normal 2, 6
Organ Dysfunction Variables:
- Arterial hypoxemia (PaO2/FiO2 <300) 2
- Acute oliguria (urine output <0.5 mL/kg/h for ≥2 hours despite adequate fluid resuscitation) 2
- Creatinine increase >0.5 mg/dL or 44.2 μmol/L 2
- Coagulation abnormalities (INR >1.5 or aPTT prolongation) 2
- Thrombocytopenia (platelet count <100,000/μL) 2
- Hyperbilirubinemia (total bilirubin >4 mg/dL or 70 μmol/L) 2
Tissue Perfusion Variables:
Critical Pitfalls and Caveats
The Sepsis-3 guidelines explicitly discontinued the use of SIRS criteria for sepsis classification, though SIRS remains useful as a screening tool. 2, 5 Research demonstrates that SIRS has poor discriminatory capacity (AUROC 0.57) compared to SOFA and qSOFA. 7
Important caveat regarding white blood cell counts: A normal WBC count does NOT exclude sepsis. 6 The presence of >10% immature forms (left shift) has a likelihood ratio of 14.5 for bacterial infection, making it far more valuable than the total WBC count alone. 6 In neutropenic patients, WBC count cannot be used as a diagnostic criterion and must be removed from consideration entirely. 6
Lactate measurement is advised as an important component of initial evaluation, but elevated lactate levels are no longer part of organ dysfunction criteria to define sepsis—they are reserved for defining septic shock. 2 However, lactate demonstrates independent prognostic value with discriminative ability (AUROC 0.664) similar to SOFA. 8
Pediatric Considerations
In children, sepsis requires signs of inflammation plus infection with: 1
- Hyper- or hypothermia (rectal temperature >38.5°C or <35°C) 1
- Tachycardia (may be absent in hypothermia) 1
- At least one of: altered mental status, hypoxemia, increased lactate, or bounding pulses 1
Maternal Sepsis Modifications
For pregnant patients (20 weeks gestation through 3 days postpartum), use obstetrically modified SIRS (omSIRS) as the initial screening step, followed by assessment for end-organ injury with obstetrically modified laboratory criteria. 2 This two-step approach was introduced by the California Maternal Quality Care Collaborative (CMQCC) to account for physiologic changes during pregnancy. 2
Practical Clinical Algorithm
When evaluating a patient with suspected infection:
- Confirm documented or strongly suspected infection 1
- Calculate SOFA score immediately (or qSOFA if outside ICU) 1, 3
- If SOFA increase ≥2 points from baseline → diagnose sepsis 1
- If qSOFA ≥2 outside ICU → calculate full SOFA score 3
- Assess for septic shock: persistent hypotension or lactate >4 mmol/L after fluid resuscitation 2
- Obtain blood cultures, procalcitonin, and lactate 1
- Identify source with appropriate imaging (ultrasound first for suspected urosepsis, CT if negative) 1