What is systemic inflammatory response syndrome (SIRS) and its diagnostic criteria?

What is Systemic Inflammatory Response Syndrome (SIRS)?

SIRS is a clinical syndrome diagnosed when a patient meets at least two of four specific criteria: temperature >38°C or <36°C, heart rate >90 beats/min, respiratory rate >20 breaths/min (or PaCO₂ <32 mmHg), and white blood cell count >12,000/mm³ or <4,000/mm³ or >10% immature band forms. 1, 2, 3

Diagnostic Criteria

SIRS requires ≥2 of the following 4 parameters to be present: 1, 2, 3

• Temperature: >38°C or <36°C 1
• Heart rate: >90 beats/min 1
• Respiratory rate: >20 breaths/min OR PaCO₂ <32 mmHg (4.3 kPa) 1
• White blood cell count: >12,000/mm³ OR <4,000/mm³ OR >10% immature (band) forms 1

These criteria can be obtained entirely at the bedside without requiring pathological specimens, cultures, or advanced imaging. 2, 3

Clinical Significance

SIRS represents the body's acute phase inflammatory response to diverse insults—both infectious and non-infectious. 1, 2, 4

Common Triggers Include:

• Infectious causes: Sepsis, pneumonia, urinary tract infections, diabetic foot infections 2
• Tissue injury: Surgery, trauma, hematoma, venous thrombosis 2
• Cardiovascular events: Myocardial infarction, pulmonary infarction 2
• Other conditions: Pancreatitis, transplant rejection, subarachnoid hemorrhage, even chronic salicylate toxicity 2, 5

Major trauma is the main cause of non-septic SIRS, triggered by tissue necrosis, hemorrhage, and ischemia-reperfusion injury. 1

Pathophysiology

SIRS involves a complex cascade of pro- and anti-inflammatory mediators: 6

• Neuroendocrine changes: Fever, somnolence, fatigue, anorexia, increased cortisol/adrenaline/glucagon secretion 2
• Hematopoietic changes: Anemia, leukocytosis, thrombocytosis 2
• Metabolic changes: Muscle catabolism, negative nitrogen balance, increased lipolysis, trace metal sequestration, diuresis 2
• Hepatic changes: Increased blood flow, elevated acute phase protein production 2

Cytokines drive catabolism of glycogen, fat, and protein stores to release glucose, free fatty acids, and amino acids for tissue healing. 2

Differentiation from Related Conditions

SIRS differs fundamentally from sepsis, which requires SIRS criteria PLUS confirmed or suspected infection. 3

• Septic shock: Sepsis with persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND lactate >2 mmol/L despite adequate fluid resuscitation 3, 7
• Septicemia: Requires blood culture confirmation of bacteria in the bloodstream 3
• Hemorrhagic shock: Inadequate tissue perfusion from blood loss, requiring confirmation of bleeding source 3

Clinical Implications and Monitoring

The magnitude of SIRS correlates directly with surgical trauma severity and predicts poorer outcomes. 2

• Persistent SIRS >48 hours: 25.4% mortality versus 8% with transient SIRS and 0.7% without SIRS 2
• C-reactive protein (CRP): The prototypical SIRS biomarker that consistently reflects inflammation magnitude and can track response trajectory 2, 7
• Procalcitonin ≥1.5 ng/mL and CRP ≥50 mg/L: Support infectious etiology, though no single biomarker definitively distinguishes sepsis from SIRS 7

In diabetic foot infections, presence of ≥2 SIRS criteria automatically classifies the infection as severe (Grade 4) and mandates aggressive therapy. 1, 2

Management Principles

Management focuses on identifying and treating the underlying cause while providing supportive care. 2, 7

Key Management Steps:

• Obtain cultures before antibiotics if infection is suspected; if impossible, draw immediately before the next antibiotic dose 7
• Initiate broad-spectrum antimicrobials immediately after obtaining cultures if infection is suspected, as delay worsens outcomes 7
• Perform urgent source control (drainage, debridement, device removal) as delay increases mortality 7
• Fluid resuscitation: Minimum 20 mL/kg crystalloid bolus for hypotension or hypoperfusion signs, targeting near-zero fluid balance 7
• Vasopressor support: Norepinephrine as first-line for hypotension requiring vasopressors, targeting MAP ≥65 mmHg 7

Critical Pitfalls to Avoid:

• Do not delay antibiotics in suspected severe infection while waiting for "optimization"—the patient may die before adequate resuscitation 7
• Do not assume SIRS in the first 48 hours post-operatively represents infection—it may reflect surgical stress alone, but do not delay cultures/antibiotics if specific infection indicators are present 7
• Reassess within 48 hours: Persistence of SIRS criteria beyond this timeframe indicates high mortality risk and requires escalation 2, 7

Historical Context

SIRS was defined in 1991 to provide readily available clinical markers for early identification of patients who might benefit from anti-inflammatory interventions in sepsis trials. 8 The definition prioritized sensitivity and bedside availability over specificity, recognizing that diverse injuries produce a common inflammatory response with attractive therapeutic targets. 8, 9