SEPSIS BIOMARKER: CURRENT CONCEPT

Sepsis biomarkers: Current Concept

Lactate, C-reactive protein (CRP), and procalcitonin (PCT) are commonly used for classification and management of septic patients. Lactate is used to assess tissue perfusion and is elevated with tissue hypoxia caused by hypoperfusion in severe sepsis and septic shock but not in early sepsis. The SSC guidelines recommend measuring lactate within three hours after sepsis is suspected; a lactate > 4 mmol/L warrants fluid resuscitation. If initial concentration is above that cut-off, lactate is remeasured within a few hours to evaluate response to therapy. Patients achieving a lactate clearance > 10% have better prognoses.

CRP and PCT are both inflammatory biomarkers, widely investigated for sepsis diagnosis. CRP is an acute-phase reactant elevated in many inflammatory conditions. PCT, the precursor of the thyroid hormone calcitonin, is also increased in the systemic inflammatory response to infection. The Food and Drug Administration-approved PCT testing is indicated in conjunction with other laboratory and clinical findings for the diagnosis of bacterial infection and sepsis in critically ill patients. Overall, most studies indicate superior clinical utility (sensitivity and specificity) of PCT over CRP for the identification of sepsis among patients with systemic inflammation. The concentration of PCT correlates with severity of disease, while CRP is not helpful for stratification.

The utility of PCT remains controversial and it is not universally adopted in clinical practice. Both CRP and PCT are listed among the inflammatory variables that serve as criteria to diagnose sepsis, but the SSC guidelines state that the ability of PCT or CRP to discriminate between non-infectious and infectious SIRS has not been demonstrated, and they issue no recommendations for utilization of either biomarker to identify infected patients among those with systemic inflammation. The SSC guidelines endorse PCT as a tool for antibiotic stewardship. In adults, low PCT concentrations can be used to direct cessation of antibiotics in critically ill patients; however, high PCT concentrations should not be used to intensify antibiotic therapy. The utility of PCT is still unknown in pediatric patients and neonates. PCT-guided antimicrobial therapy reduces antibiotic use without benefits in morbidity and mortality.

In sum, lactate, PCT, and CRP are helpful markers to manage patients with suspected sepsis by providing prognostic information and guiding therapy, but they have limited diagnostic utility in sepsis and no role at the early stages of sepsis.