What are the classic signs of sepsis?

Classic Signs of Sepsis

Sepsis is characterized by a systemic inflammatory response to infection with specific diagnostic criteria including fever or hypothermia, tachycardia, tachypnea, altered mental status, and evidence of organ dysfunction. 1

Core Vital Sign Abnormalities

The classic signs of sepsis center on abnormal vital signs that reflect the body's inflammatory response:

• Fever is defined as core temperature >38.3°C, or hypothermia as core temperature <36°C 2, 1
• Tachycardia is defined as heart rate >90 beats per minute or >2 standard deviations above normal for age 2, 1
• Tachypnea is defined as respiratory rate >20-30 breaths per minute 2, 1
• Altered mental status is a key clinical sign that should raise immediate concern for sepsis 2, 1

Hemodynamic and Perfusion Signs

Tissue hypoperfusion manifests through several classic findings:

• Arterial hypotension defined as systolic blood pressure <90 mmHg, mean arterial pressure <70 mmHg, or systolic blood pressure decrease >40 mmHg 2, 1
• Decreased capillary refill or skin mottling indicates poor peripheral perfusion 2, 1
• Peripheral cyanosis may be present 1
• Hyperlactatemia (>1 mmol/L) indicates tissue hypoperfusion and is a critical marker 1

Organ Dysfunction Parameters

Sepsis progresses to severe sepsis when organ dysfunction develops:

• Acute oliguria defined as urine output <0.5 mL/kg/h for at least 2 hours despite adequate fluid resuscitation 2, 1
• Arterial hypoxemia with PaO₂/FiO₂ ratio <300, often accompanied by severe dyspnea and tachypnea 2, 1
• Creatinine increase ≥0.5 mg/dL indicates renal dysfunction 2, 1
• Coagulation abnormalities with INR >1.5 or aPTT >60 seconds 2, 1
• Thrombocytopenia with platelet count <100,000/μL 2, 1
• Hyperbilirubinemia with plasma total bilirubin >4 mg/dL 2, 1
• Ileus manifested by absent bowel sounds 2, 1

Laboratory and Inflammatory Markers

• Leukocytosis (WBC >12,000/μL) or leukopenia (WBC <4,000/μL), or normal WBC with >10% immature forms 1
• Elevated C-reactive protein or procalcitonin >2 standard deviations above normal 2, 1
• Hyperglycemia with plasma glucose >140 mg/dL in the absence of diabetes 1

Systemic Symptoms Beyond Vital Signs

Recent evidence demonstrates that certain systemic symptoms predict severe sepsis development:

• Muscle weakness is significantly associated with severe sepsis (OR 2.24) 3
• Dyspnea strongly predicts severe sepsis (OR 2.92) 3
• Gastrointestinal symptoms including nausea, vomiting, or diarrhea (OR 2.31) 3
• Significant edema or positive fluid balance >20 mL/kg over 24 hours 2, 1

Critical Pitfalls to Avoid

In neutropenic patients, white blood cell count cannot be used as a criterion to define sepsis, as these patients may not mount a leukocytosis despite severe infection 2, 1. The other classic signs remain valid and critical for diagnosis in this population.

The presence of altered mental status combined with other signs of infection should be considered a warning sign of severe sepsis, as it indicates cerebral hypoperfusion and warrants immediate aggressive management 3.

Septic shock represents the most severe form, defined as severe sepsis with persistent hypotension despite adequate fluid resuscitation, requiring vasopressor support 2, 1, 4. Mortality in septic shock can reach 80%, emphasizing the critical importance of recognizing earlier signs 4.