What are the key components and management strategies of the Sepsis-3 concept for identifying and treating sepsis?

Sepsis-3 Concept: Key Components and Management

Core Definition and Diagnostic Criteria

Sepsis-3 fundamentally redefines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as an acute increase in Sequential Organ Failure Assessment (SOFA) score of ≥2 points, which correlates with in-hospital mortality >10%. 1, 2

Critical Conceptual Changes from Prior Definitions

• The term "severe sepsis" is now obsolete and should not be used 2
• SIRS criteria are no longer required for sepsis diagnosis, representing a major departure from the 1991 and 2001 consensus definitions 1, 3
• The focus shifts from inflammatory markers to organ dysfunction as the defining feature 3, 4

Septic Shock Definition

Septic shock is defined as a subset of sepsis requiring vasopressor therapy to maintain mean arterial pressure (MAP) ≥65 mmHg AND serum lactate >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation 1, 2

• This definition identifies patients with particularly profound circulatory, cellular, and metabolic abnormalities associated with higher mortality risk than sepsis alone 1

Screening and Identification Tools

Quick SOFA (qSOFA) Score

qSOFA serves as a bedside screening tool outside the ICU to identify patients with suspected infection at high risk for poor outcomes, NOT as a diagnostic criterion for sepsis itself 1, 2, 5

The three qSOFA criteria (1 point each):

• Respiratory rate ≥22 breaths/minute 1, 2, 5
• Altered mental status (Glasgow Coma Scale <15 or <14 depending on source) 1, 2, 5
• Systolic blood pressure ≤100 mmHg 1, 2, 5

A qSOFA score ≥2 indicates high-risk patients requiring immediate full SOFA assessment and consideration for ICU-level care 2, 5

Important Caveats About qSOFA

• qSOFA has poor sensitivity (16.3%) in the prehospital setting for identifying severe sepsis/septic shock, though specificity is high (97.3%) 6
• The dynamic nature of sepsis means patients may not meet qSOFA criteria early in their course, predominantly due to blood pressure and respiratory rate not yet reaching thresholds 6
• In burn patients, qSOFA sensitivity is 84.1% with specificity 92.9%, outperforming traditional SIRS criteria for specificity 7

Full SOFA Score Components

The SOFA score assesses six organ systems (0-4 points each) 2:

Respiratory:

• PaO2/FiO2 <400: 1 point
• <300: 2 points
• <200 with mechanical ventilation: 3 points
• <100 with mechanical ventilation: 4 points 2

Cardiovascular:

• MAP <70 mmHg: 1 point
• Dopamine ≤5 or dobutamine (any dose): 2 points
• Dopamine >5 OR epinephrine ≤0.1 OR norepinephrine ≤0.1 mcg/kg/min: 3 points
• Dopamine >15 OR epinephrine >0.1 OR norepinephrine >0.1 mcg/kg/min: 4 points 2

Hepatic: Bilirubin >1.2 mg/dL scores points 2

Coagulation: Platelets <150,000/μL 2

Renal: Creatinine >3.5 mg/dL or urine output <500 mL/day 2

Neurological: Glasgow Coma Scale assessment 2

Management Algorithm

Immediate Actions (Within First Hour)

1. Administer broad-spectrum intravenous antibiotics within the first hour of recognition 1, 2

• This is a Grade 1B recommendation for septic shock and Grade 1C for sepsis without shock 1
• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before antibiotics if no significant delay (<45 minutes) 1

2. Initiate aggressive fluid resuscitation with crystalloid solutions 1

• Target initial hemodynamic resuscitation within 3 hours 1
• Crystalloids are first choice because they are well-tolerated and cost-effective 1

3. Start vasopressor therapy if hypotension persists after initial fluid challenge 1

• Norepinephrine is the first-line vasopressor agent, more efficacious than dopamine 1
• Target MAP ≥65 mmHg 1

Resuscitation Goals (First 6 Hours)

The following targets should guide initial resuscitation 1:

• Central venous pressure 8-12 mmHg (Grade 1C)
• MAP ≥65 mmHg (Grade 1C)
• Urine output ≥0.5 mL/kg/hour (Grade 1C)
• Central venous oxygen saturation ≥70% or mixed venous ≥65% (Grade 1C)
• Normalize lactate as rapidly as possible in patients with elevated levels (Grade 2C) 1

Source Control

Identify and control the anatomical source of infection within the first 12 hours after diagnosis 1, 2

• This includes surgical intervention when indicated (abscess drainage, debridement of necrotic tissue, removal of infected devices) 1, 2
• For intra-abdominal infections, the five pillars are: prompt diagnosis, adequate resuscitation, early appropriate antibiotics, early effective source control, and reassessment with adjustment 1

Antimicrobial Management

Initial empiric therapy should cover all likely pathogens with adequate tissue penetration 1

Key principles:

• Reassess antimicrobial regimen daily for potential de-escalation (Grade 1B) 1
• De-escalation to single appropriate therapy once susceptibility known, typically after 3-5 days of combination therapy 1
• Typical duration 7-10 days, longer for slow clinical response, undrained foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiency 1
• De-escalation is feasible and safe in polymicrobial infections like healthcare-associated intra-abdominal infections and is a protective factor for mortality 1

Ongoing Monitoring and Escalation

Calculate serial SOFA scores every 48-72 hours to track organ dysfunction trajectory 2

• Worsening scores indicate poor prognosis and need for intervention escalation 2
• Transfer to ICU-level care when qSOFA ≥2, as this predicts need for intensive respiratory or vasopressor support 2

Mechanical Ventilation (If ARDS Develops)

Target tidal volume of 6 mL/kg predicted body weight (Grade 1A) 1

• Plateau pressures ≤30 cm H2O (Grade 1B) 1
• Apply PEEP to avoid alveolar collapse (Grade 1B) 1
• Prone positioning for PaO2/FiO2 ratio ≤100 mmHg in experienced facilities (Grade 2B) 1
• Head of bed elevated 30-45 degrees to prevent ventilator-associated pneumonia (Grade 1B) 1

Blood Products

Transfuse RBCs only when hemoglobin <7.0 g/dL, targeting 7.0-9.0 g/dL once tissue hypoperfusion resolved (Grade 1B) 1

• Do not use antithrombin (Grade 1B) 1
• Prophylactic platelets when <10,000/mm³ without bleeding, <20,000/mm³ with bleeding risk, ≥50,000/mm³ for active bleeding/surgery (Grade 2D) 1

Corticosteroids

Do not administer corticosteroids for sepsis in the absence of shock (Grade 1D) 1

• When hydrocortisone is given in septic shock, use continuous infusion (Grade 2D) 1

Special Populations and Considerations

Age-Related Factors

Octogenarians and nonagenarians may present with fewer signs of peritonitis and attenuated inflammatory response, making diagnosis more challenging 1

Immunocompromised Patients

HIV-infected patients have increased sepsis risk due to immune system dysfunction, with relatively poorer outcomes even on antiretroviral therapy 1

Sepsis-Induced Coagulopathy (SIC)

Calculate SIC score (platelet count + PT ratio + SOFA score) for patients with thrombocytopenia 2

• SIC score ≥4 identifies coagulopathy requiring specific interventions 2
• SIC-positive patients have higher mortality (32.5-37.2%) 2

Common Pitfalls to Avoid

Do not rely solely on qSOFA for diagnosis - it is a screening tool, not a diagnostic criterion; full SOFA assessment is required 2, 5

Do not delay antibiotics waiting for cultures - obtain cultures quickly but do not delay antibiotics beyond 45 minutes 1

Do not use SIRS criteria as a requirement - the Sepsis-3 definition explicitly removes SIRS from the diagnostic framework 1, 3

Do not overlook the dynamic nature of sepsis - patients may not meet criteria initially, requiring serial reassessment 6

Do not use pulmonary artery catheters routinely in sepsis-induced ARDS (Grade 1A) 1