What factors can cause falsely elevated procalcitonin levels?

Factors Causing Falsely Elevated Procalcitonin

Procalcitonin can be falsely elevated by non-infectious conditions including shock states (cardiogenic, hemorrhagic), hyperinflammatory states (particularly COVID-19 cytokine storm), drug hypersensitivity reactions, malignant hyperthermia, neuroleptic malignant syndrome, major surgery/trauma, and early sampling within 6 hours of admission. 1, 2

Non-Infectious Causes of PCT Elevation

Shock States and Hemodynamic Instability

• Cardiogenic and hemorrhagic shock can elevate PCT levels independent of bacterial infection, making interpretation challenging in critically ill patients 1
• Uncomplicated cardiac surgery induces postoperative PCT increases that peak within 24 hours and return to normal within the first week, with the magnitude dependent on surgical procedure and intraoperative events 3

Hyperinflammatory Conditions

• COVID-19 infection causes falsely elevated PCT in approximately 21% of patients without bacterial pneumonia due to cytokine storm and hyperinflammatory status 1
• The hyperinflammatory response in COVID-19 results in higher PCT production than other viral pneumonias, confounding interpretation for bacterial coinfection 4
• This is particularly problematic in critically ill COVID-19 patients where distinguishing viral inflammation from bacterial superinfection is crucial 2

Drug Reactions and Toxidromes

• Drug hypersensitivity reactions can cause significant PCT elevation without bacterial infection 1
• Anaphylactic shock has been documented to cause extremely high PCT levels, as demonstrated in a case report of anaphylaxis from parasitic infestation 5
• Malignant hyperthermia and neuroleptic malignant syndrome are rare but serious conditions associated with elevated PCT 1

Surgical and Traumatic Conditions

• Major surgery and trauma can elevate PCT through systemic inflammatory response syndrome (SIRS) without infection 1, 3
• The magnitude of PCT elevation post-surgery correlates with the invasiveness of the procedure and intraoperative complications 3

Timing-Related False Results

Early Sampling Issues

• PCT sampling within 6 hours of admission may produce false-negative results, not false-positive, but this timing issue is critical for interpretation 4, 2
• The negative predictive value of PCT for bacterial coinfection is more accurate when sampled on the day after admission rather than day 0 4
• PCT levels typically rise within 2-3 hours of infection onset, so very early sampling may miss the rise 1

Clinical Interpretation Pitfalls

Context-Dependent Elevation

• PCT should never be used alone to guide clinical decisions - it must be integrated with clinical assessment, imaging, and other laboratory findings 1, 6
• In patients with high probability of bacterial infection based on clinical criteria, PCT should not be measured to rule out infection 1
• Certain bacterial pathogens like Legionella and Mycoplasma may not elevate PCT even with true infection, creating false-negative rather than false-positive results 1

Autoimmune and Inflammatory Conditions

• Autoimmune diseases and non-infectious inflammatory responses can cause slight to moderate PCT increases 7, 5
• Acute respiratory distress syndrome (ARDS) and pancreatitis of non-infectious origin may elevate PCT 8

Practical Approach to Suspected False Elevation

When encountering elevated PCT without clear bacterial infection:

• Consider non-infectious causes systematically: recent surgery/trauma, shock states, drug reactions, and COVID-19 or other viral infections with hyperinflammation 1, 6
• Serial PCT measurements are more valuable than single readings - trending PCT over 24-48 hours helps distinguish true bacterial infection (rising PCT) from false elevation (stable or declining PCT) 1, 6, 2
• A 50% rise in PCT from baseline is more predictive of secondary bacterial infection than absolute values in critically ill patients 4
• Do not delay empiric antibiotics if bacterial infection is clinically suspected, regardless of PCT level, as the sensitivity for bacterial infection ranges only 38-91% 1, 6