What is the definition of sepsis, how is it diagnosed (including qSOFA and lactate criteria), and what are the initial management steps (source control, antimicrobial therapy, fluid resuscitation, vasopressors, and supportive care)?

Sepsis: Definition, Diagnosis, and Management

Definition

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, operationally defined as an acute increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points from baseline. 1, 2, 3

• The SOFA score increase of ≥2 points correlates with in-hospital mortality exceeding 10%. 1, 2
• The term "severe sepsis" is obsolete and should not be used. 2, 3
• Sepsis requires both an aberrant host response AND organ dysfunction—not just infection alone. 1

Septic Shock Definition

Septic shock is identified by the requirement for vasopressors to maintain mean arterial pressure (MAP) ≥65 mmHg AND serum lactate >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation. 4, 2, 3

• Septic shock carries >40% mortality risk. 1
• This represents particularly profound circulatory, cellular, and metabolic abnormalities with higher mortality than sepsis alone. 4, 3

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Diagnosis and Screening

Quick SOFA (qSOFA) Score

The qSOFA provides simple bedside criteria to screen patients with suspected infection for high risk of poor outcomes, but does NOT define sepsis. 4, 3

qSOFA criteria (1 point each):

• Respiratory rate ≥22 breaths/min 4, 3
• Altered mental status (Glasgow Coma Scale ≤14 or ≤13) 4, 3
• Systolic blood pressure ≤100 mmHg 4, 3

A qSOFA score ≥2 indicates high risk and warrants immediate full SOFA assessment and consideration of ICU-level care. 2, 3

NEWS2 Score (Alternative Screening Tool)

The 2024 NICE guideline recommends NEWS2 over qSOFA for initial bedside risk stratification in emergency and acute care settings. 2

NEWS2 risk categories and actions:

• Score ≥7 (high risk): Re-assess every 30 minutes; administer antibiotics within 1 hour; immediate senior review and ICU consideration 2
• Score 5-6 (moderate risk): Re-assess hourly; antibiotics within 3 hours 2
• Score 1-4 (low risk): Re-assess every 4-6 hours; antibiotics within 6 hours 2
• Score 0 (very low risk): No immediate escalation required 2

Critical override: Any single NEWS2 parameter scoring 3 points or presence of purpuric rash upgrades risk regardless of total score. 2

Full SOFA Score

The full SOFA score is the definitive diagnostic tool for sepsis, assessing six organ systems (0-4 points each). 2

SOFA components:

• Respiratory: PaO2/FiO2 ratio (<400: 1 point; <300: 2 points; <200 with ventilation: 3 points; <100 with ventilation: 4 points) 2
• Cardiovascular: MAP and vasopressor requirements (MAP <70 mmHg: 1 point; escalating vasopressor doses: 2-4 points) 2
• Hepatic: Bilirubin levels (>1.2 mg/dL scores points) 2
• Coagulation: Platelet count (<150,000/μL scores points) 2
• Renal: Creatinine and urine output (creatinine >3.5 mg/dL or urine <500 mL/day: higher points) 2
• Neurological: Glasgow Coma Scale 2

Lactate Measurement

Measure serum lactate in all patients with suspected sepsis; lactate ≥4 mmol/L indicates severe hypoperfusion requiring aggressive resuscitation. 4, 1

• Lactate >2 mmol/L in the presence of vasopressor requirement defines septic shock. 4, 3
• Serial lactate measurements guide adequacy of resuscitation. 4

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Initial Management

1. Source Control and Antimicrobial Therapy

Administer broad-spectrum intravenous antibiotics within 1 hour of sepsis recognition—this is the single most critical intervention for mortality reduction. 1, 2

• Early antimicrobial therapy significantly impacts survival compared to delayed or inappropriate treatment. 4, 3
• Identify and control the source of infection urgently; surgical intervention is required for conditions like perforated viscus or necrotizing soft tissue infections. 2
• Blood cultures should be obtained before antibiotics when possible, but never delay antibiotics beyond 1 hour. 2, 3

Common pitfall: Do not wait for culture results or complete diagnostic workup before starting antibiotics in high-risk patients. 2

2. Fluid Resuscitation

Administer 30 mL/kg of crystalloid solution rapidly for hypotension or lactate ≥4 mmol/L within the first 3 hours. 4, 1

Crystalloid solutions are the first-line choice because they are well-tolerated and cost-effective. 4

• Balanced crystalloids are preferred over normal saline when possible. 1
• Fluid boluses should be administered rapidly (250-1000 mL) to induce quick hemodynamic response. 4
• Human albumin solution may be considered as second-line in refractory shock or when large crystalloid volumes are required. 4

Critical caveat: Avoid fluid overload, particularly in patients with generalized peritonitis, as this aggravates bowel edema and increases intra-abdominal pressure, potentially leading to abdominal compartment syndrome. 4

3. Vasopressor Therapy

Norepinephrine is the first-line vasopressor agent for septic shock. 4, 1

• Norepinephrine is more efficacious than dopamine and more effective for reversing hypotension in septic shock. 4
• Target MAP of 65-70 mmHg is the initial hemodynamic goal. 4, 1
• Vasopressors should be initiated promptly if hypotension persists despite adequate fluid resuscitation. 4

4. Monitoring and Supportive Care

Serial SOFA score calculations every 48-72 hours track organ dysfunction trajectory and guide escalation decisions. 2

Specific organ support based on SOFA components:

• Respiratory failure: Provide appropriate oxygen therapy or mechanical ventilation based on PaO2/FiO2 ratio; consider intubation if <200 mmHg. 2
• Renal dysfunction: Monitor urine output and creatinine closely; consider early renal replacement therapy if creatinine >3.5 mg/dL or urine output <500 mL/day. 2
• Coagulopathy: Monitor platelet count and address coagulopathy if platelets <150,000/μL; calculate Sepsis-Induced Coagulopathy (SIC) score if thrombocytopenia present (SIC ≥4 indicates 32.5-37.2% mortality). 2

5. ICU Transfer and Multidisciplinary Care

Transfer patients with qSOFA ≥2 or NEWS2 ≥7 to ICU-level care, as these scores predict need for intensive respiratory or vasopressor support. 2

• Coordinate multidisciplinary care involving intensivists, infectious disease specialists, and surgeons as needed. 2
• Worsening SOFA scores indicate poor prognosis and need for escalation of interventions. 2

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Key Clinical Pitfalls

Do not rely on qSOFA alone for sepsis diagnosis—it is a screening tool with low sensitivity; use full SOFA score for definitive diagnosis. 2

Do not delay antibiotics beyond 1 hour in high-risk patients (qSOFA ≥2, NEWS2 ≥7)—early antimicrobial therapy is critical for mortality reduction. 2

Avoid aggressive fluid resuscitation without monitoring for fluid overload—excessive fluids increase intra-abdominal pressure and risk abdominal compartment syndrome, particularly in peritonitis. 4

Do not use dopamine as first-line vasopressor—norepinephrine is superior for reversing hypotension and improving outcomes. 4

Recognize that elderly and immunocompromised patients may present atypically with attenuated inflammatory responses despite severe infection. 3