What are the diagnostic and treatment criteria for sepsis?

Diagnosing and Treating Sepsis: Essential Information

To diagnose and treat sepsis effectively, you must immediately recognize infection with organ dysfunction, obtain blood cultures without delaying antibiotics beyond 45 minutes, administer IV antimicrobials within the first hour, and give at least 30 mL/kg IV crystalloid within 3 hours while targeting a mean arterial pressure ≥65 mmHg. 1

Diagnostic Criteria

Core Definition

• Sepsis is life-threatening organ dysfunction caused by dysregulated host response to infection 2, 3
• Suspect sepsis in any patient with suspected or documented infection PLUS evidence of organ dysfunction 4

Clinical Parameters to Assess

Vital Signs and Physical Findings:

• Core temperature >38.3°C or <36°C 3
• Heart rate >90 beats/min 3
• Respiratory rate >20 breaths/min 3
• Systolic blood pressure <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg 3
• Altered mental status 2, 3
• Decreased capillary refill, skin mottling, or peripheral cyanosis 3
• Urine output <0.5 mL/kg/hr for ≥2 hours despite adequate fluid resuscitation 3

Laboratory Markers:

• WBC >12,000/μL or <4,000/μL, or >10% immature forms 3
• Lactate >1 mmol/L (elevated lactate indicates tissue hypoperfusion) 1, 3
• Creatinine increase ≥0.5 mg/dL or >2.0 mg/dL for severe sepsis 3
• Bilirubin >2 mg/dL for severe sepsis 3
• Platelet count <100,000/μL 3
• INR >1.5 or aPTT >60 seconds 3
• PaO₂/FiO₂ <300 3

Septic Shock Criteria

Septic shock is defined as persistent hypotension despite adequate fluid resuscitation requiring vasopressors to maintain MAP ≥65 mmHg, with lactate >2 mmol/L 2, 4

Diagnostic Workup

Immediate Actions (Within 45 Minutes)

Microbiologic Cultures: 1

• Obtain at least 2 sets of blood cultures (aerobic and anaerobic bottles) before antimicrobials
• Draw at least 1 percutaneously and 1 through each vascular access device (unless device inserted <48 hours ago)
• Do not delay antimicrobials beyond 45 minutes to obtain cultures

Biomarkers for Risk Stratification:

• Procalcitonin (PCT): Rises within 4 hours, peaks at 6-8 hours; levels ≥1.5 ng/mL show 100% sensitivity and 72% specificity for sepsis 2
• C-Reactive Protein (CRP): Rises 12-24 hours after insult; levels ≥50 mg/L show 98.5% sensitivity and 75% specificity 2
• Lactate: Measure immediately; use serial measurements to guide resuscitation 1

Important caveat: Biomarkers should not be used in isolation to exclude sepsis—they must be part of systematic clinical evaluation 2

Source Identification

Imaging Studies:

• Perform promptly to confirm potential infection source 1
• Target imaging based on suspected source: chest X-ray for pneumonia, CT abdomen/pelvis for intra-abdominal infection, ultrasound for biliary/renal sources 4

Additional Testing for Specific Scenarios:

• 1,3-β-D-glucan assay, mannan and anti-mannan antibodies if invasive candidiasis suspected 1

Treatment Protocol

Hour 1: Antimicrobial Therapy (CRITICAL)

Timing is everything: 1

• Administer effective IV antimicrobials within the first hour of recognizing septic shock or severe sepsis
• This is a strong recommendation with high-quality evidence for septic shock

Antibiotic Selection: 1

• Use one or more broad-spectrum drugs active against all likely pathogens (bacterial, fungal, or viral)
• Ensure adequate tissue penetration to presumed infection source
• Combination therapy is recommended for:
  • Neutropenic patients with severe sepsis
  • Multidrug-resistant pathogens (Acinetobacter, Pseudomonas)
  • Severe infections with respiratory failure and septic shock from P. aeruginosa (extended-spectrum β-lactam + aminoglycoside or fluoroquinolone)
  • Septic shock from S. pneumoniae bacteremia (β-lactam + macrolide)

Daily Reassessment: 1

• Reassess antimicrobial regimen daily for potential de-escalation
• Use procalcitonin or similar biomarkers to assist discontinuation in patients without confirmed infection
• Combination therapy should not exceed 3-5 days; de-escalate to single agent once susceptibilities known
• Typical duration: 7-10 days (longer for slow clinical response)

Hours 1-3: Fluid Resuscitation

Initial Fluid Bolus: 1

• Give at least 30 mL/kg IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion
• This is a strong recommendation despite low-quality evidence

Ongoing Fluid Management: 1

• Following initial resuscitation, guide additional fluids by frequent reassessment of hemodynamic status
• Reassess: heart rate, blood pressure, oxygen saturation, respiratory rate, temperature, urine output, mental status
• Use dynamic variables over static variables to predict fluid responsiveness when available

Hemodynamic Targets

Mean Arterial Pressure: 1

• Target MAP ≥65 mmHg in patients requiring vasopressors (strong recommendation, moderate-quality evidence)

Lactate Normalization: 1

• Guide resuscitation to normalize lactate in patients with elevated levels as marker of tissue hypoperfusion

Additional Monitoring (if clinical examination unclear): 1

• Perform further hemodynamic assessment (cardiac function evaluation) to determine shock type
• Consider central venous oxygen saturation monitoring in select cases

Source Control

Timing: 2

• Identify anatomic diagnosis requiring source control as rapidly as possible
• Implement source control measures within 12 hours when feasible

Screening and Performance Improvement

Hospital Systems Should: 1

• Implement routine sepsis screening for acutely ill, high-risk patients
• Maintain performance improvement programs for sepsis management

Common Pitfalls to Avoid

• Never delay antimicrobials beyond 1 hour waiting for culture results or additional testing 1
• Do not rely solely on biomarkers (PCT, CRP) to exclude sepsis—clinical judgment is paramount 2
• Avoid excessive fluid resuscitation—reassess frequently and use dynamic variables 1
• Do not use WBC count as sepsis criterion in neutropenic patients 3
• Remember that normal lactate does not exclude sepsis—some patients with ongoing sepsis may not have elevated lactate 1