Diagnostic Guidelines for Sepsis
Sepsis should be diagnosed using a combination of clinical criteria for infection plus evidence of organ dysfunction, with specific laboratory and clinical parameters outlined in the Surviving Sepsis Campaign guidelines. 1
Definition and Diagnostic Criteria
Sepsis Definition
- Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection 2
- This represents a shift from earlier definitions that focused primarily on inflammatory response 1
Diagnostic Criteria for Sepsis
- Suspected or documented infection plus some of the following criteria 1:
General Variables
- Fever (>38.3°C) or hypothermia (core temperature <36°C) 1
- Heart rate >90 min-1 or more than two standard deviations above normal for age 1
- Tachypnea 1
- Altered mental status 1
- Significant edema or positive fluid balance (>20 mL/kg over 24h) 1
- Hyperglycemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in the absence of diabetes 1
Inflammatory Variables
- Leukocytosis (WBC count >12,000 μL-1) 1
- Leukopenia (WBC count <4,000 μL-1) 1
- Normal WBC count with >10% immature forms 1
- Plasma C-reactive protein more than two standard deviations above normal 1, 3
- Plasma procalcitonin more than two standard deviations above normal 1, 4
Hemodynamic Variables
- Arterial hypotension (SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg in adults) 1
Organ Dysfunction Variables
- Arterial hypoxemia (PaO2/FiO2 <300) 1
- Acute oliguria (urine output <0.5 mL/kg/h for at least 2h despite adequate fluid resuscitation) 1
- Creatinine increase >0.5 mg/dL or 44.2 μmol/L 1
- Coagulation abnormalities (INR >1.5 or aPTT prolonged) 1
- Ileus (absent bowel sounds) 1
- Thrombocytopenia (platelet count <100,000 μL-1) 1
- Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L) 1
Tissue Perfusion Variables
Severe Sepsis Definition
- Severe sepsis is defined as sepsis-induced tissue hypoperfusion or organ dysfunction with any of the following 1:
- Sepsis-induced hypotension 1
- Lactate above upper limits of laboratory normal 1
- Urine output <0.5 mL/kg/h for more than 2h despite adequate fluid resuscitation 1
- PaO2/FiO2 <250 in the absence of pneumonia as infection source 1
- Acute lung injury with PaO2/FiO2 <200 in the presence of pneumonia as infection source 1
- Creatinine >2.0 mg/dL (176.8 μmol/L) 1
- Bilirubin >2 mg/dL (34.2 μmol/L) 1
- Platelet count <100,000 μL 1
- Coagulopathy (INR >1.5) 1
Diagnostic Approach
Screening and Early Recognition
- Hospitals should implement sepsis screening programs for acutely ill, high-risk patients 1
- Early recognition is crucial as delayed diagnosis significantly increases mortality 5, 6
Microbiological Diagnosis
- Obtain appropriate routine microbiologic cultures before starting antimicrobial therapy if doing so results in no substantial delay (>45 min) in antimicrobial administration 1
- Always include at least two sets of blood cultures (both aerobic and anaerobic bottles) 1
- One blood culture should be drawn percutaneously and one through each vascular access device (unless recently inserted <48h) 1
Biomarkers
- While no single biomarker can definitively diagnose sepsis, several can aid in diagnosis 3:
- Lactate: Elevated levels (>1 mmol/L) suggest tissue hypoperfusion; serial measurements help monitor treatment efficacy 1, 4
- Procalcitonin: More specific for bacterial infections than other inflammatory markers; useful for antimicrobial de-escalation 4, 3
- C-reactive protein: Indicates inflammation but lacks specificity for infection 4, 3
Imaging Studies
- Perform prompt imaging studies to confirm potential sources of infection 1
- Selection of imaging modality should be based on suspected source 6
- Common sources include pulmonary, urinary tract, abdominal, and skin/soft tissue infections 6
Management Implications of Diagnosis
Antimicrobial Therapy
- Administer effective IV antimicrobials within the first hour of recognition of sepsis or septic shock 1, 7
- Use broad-spectrum agents active against all likely pathogens 1
- Reassess antimicrobial regimen daily for potential de-escalation 1
Source Control
- Identify specific anatomic diagnosis of infection requiring source control as rapidly as possible 1, 7
- Implement source control measures within 12 hours of diagnosis when feasible 1, 7
- Use the least invasive approach for source control 1, 5
Fluid Resuscitation
- Administer at least 30 mL/kg of IV crystalloid fluid within the first 3 hours for patients with sepsis-induced hypoperfusion 1
- Guide additional fluid administration by frequent reassessment of hemodynamic status 1
- Target mean arterial pressure of 65 mmHg in patients with septic shock requiring vasopressors 1
Common Pitfalls in Sepsis Diagnosis
- Relying on a single biomarker to diagnose or exclude sepsis 8, 3
- Delaying antimicrobial therapy while waiting for definitive diagnosis 7, 5
- Failing to obtain appropriate cultures before starting antimicrobials 7, 5
- Not recognizing sepsis in patients with atypical presentations (elderly, immunocompromised) 6, 8
- Overlooking less common sources of infection (endocarditis, meningitis, osteomyelitis) 6
- Confusing sepsis with non-infectious causes of systemic inflammatory response 2, 8