What is the role of procalcitonin (PCT) in thermodysregulation, specifically in fever management?

Role of Procalcitonin in Thermodysregulation

Procalcitonin (PCT) does not directly regulate body temperature or thermodysregulation, but serves as a critical biomarker to distinguish infectious fever (particularly bacterial) from non-infectious causes of fever, thereby guiding appropriate management decisions in febrile patients. 1, 2

Understanding PCT's Relationship to Fever

PCT is a host-response biomarker that rises specifically in response to bacterial infections, not as a mediator of temperature regulation itself. The key distinction is:

• PCT elevates within 2-3 hours of bacterial infection onset, reaching peak levels at 6-8 hours, making it useful for early identification of bacterial causes of fever 1, 3
• Chronic inflammatory states do NOT elevate PCT, which makes it particularly valuable for distinguishing acute bacterial infections from other causes of fever 1, 2
• PCT levels correlate with infection severity along a continuum: 0.6-2.0 ng/mL for systemic inflammatory response syndrome (SIRS), 2-10 ng/mL for severe sepsis, and >10 ng/mL for septic shock 1, 4

Clinical Application in Fever Management

When to Measure PCT in Febrile Patients

Measure PCT when the probability of bacterial infection is low to intermediate and there is no clear focus of infection, as it provides complementary diagnostic information beyond clinical assessment alone 1, 2:

• PCT has 77% specificity for bacterial infections, superior to C-reactive protein (CRP) at 61% 2
• A PCT level <0.5 ng/mL helps rule out bacterial infection in patients with low-to-intermediate pretest probability 1, 5
• Do NOT measure PCT when bacterial infection probability is already high, as empiric antibiotics should be initiated regardless of PCT results 1, 2

Distinguishing Infectious from Non-Infectious Fever

PCT is most valuable for differentiating bacterial infections from other causes of fever:

• Bacterial infections: PCT significantly elevated (>0.5 ng/mL) 6, 7
• Viral infections: PCT typically remains low (<0.5 ng/mL), though severe viral illnesses (influenza, COVID-19) may cause modest elevation 2, 3
• Drug-induced fever: PCT remains low, as chronic inflammatory states do not trigger PCT elevation 1, 7
• Malignancy-related fever: PCT typically low unless concurrent bacterial infection present 8, 7
• Autoimmune/autoinflammatory diseases: PCT remains low, making it useful for excluding bacterial infection 7

Special Considerations in Neurogenic Fever

In traumatic brain injury (TBI) and other neurological conditions where thermodysregulation occurs:

• Fever control is critical regardless of the source (infectious vs. neurogenic), as elevated temperature directly increases cerebral metabolic rate, ICP, and risk of secondary brain injury 1
• Controlled normothermia should be initiated reactively when fever is detected in sedated, ventilated severe TBI patients, maintaining temperature variation ≤0.5°C per hour and ≤1°C per 24-hour period 1
• PCT can help distinguish neurogenic fever from infectious fever: neurogenic fever will have low PCT levels (<0.5 ng/mL), while bacterial infection will elevate PCT 2, 3
• When neurogenic fever is confirmed (low PCT, no infectious source), controlled normothermia should continue as long as the brain remains at risk of secondary injury 1

Practical Algorithm for PCT Use in Fever Management

1. Assess clinical probability of bacterial infection through history, examination, and initial workup 1, 5

2. If high probability of bacterial infection:

   • Do NOT wait for PCT results 1
   • Obtain blood cultures and initiate empiric antibiotics immediately 1, 2
   • Use serial PCT measurements to guide antibiotic discontinuation once patient stabilizes 2

3. If low-to-intermediate probability of bacterial infection:

   • Measure PCT as part of initial evaluation 1, 2
   • PCT <0.5 ng/mL: bacterial infection unlikely, consider non-infectious causes 5, 6
   • PCT ≥0.5 ng/mL: bacterial infection likely, initiate appropriate antimicrobial therapy 4, 6

4. Serial PCT monitoring:

   • Decreases of ≥80% from peak or levels <0.5 μg/L support antibiotic discontinuation in stabilized patients 2
   • A 50% rise from previous value indicates worsening infection or secondary bacterial infection 4

Critical Limitations and Pitfalls

• Early sampling (<6 hours from symptom onset) may produce false-negative results, as PCT requires 2-3 hours to rise and 6-8 hours to peak 3, 4
• Severe viral illnesses (influenza, COVID-19) can elevate PCT despite absence of bacterial co-infection, reducing discriminatory power 2, 3
• Renal dysfunction and renal replacement therapy markedly influence PCT levels 3
• PCT should never be used as the sole decision-making tool—always interpret in conjunction with clinical judgment 2, 5
• Antipyretics (acetaminophen, NSAIDs) have limited efficacy in controlling fever in severe TBI and neurogenic fever; automated feedback-controlled temperature management devices are superior 1