Discriminative value of inflammatory biomarkers for suspected sepsis

J Emerg Med. 2012 Jul;43(1):97-106. doi: 10.1016/j.jemermed.2011.05.072. Epub 2011 Nov 6.

Abstract

Background: Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.

Study objectives: To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.

Methods: PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.

Results: Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.

Conclusions: In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Emergency Service, Hospital
  • Female
  • Humans
  • Infections / blood
  • Infections / diagnosis
  • Interleukin-6 / blood*
  • Length of Stay
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Patient Discharge
  • Protein Precursors / blood*
  • ROC Curve
  • Sepsis / blood*
  • Sepsis / diagnosis*
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / diagnosis

Substances

  • Biomarkers
  • CALCA protein, human
  • Interleukin-6
  • Protein Precursors
  • Calcitonin
  • C-Reactive Protein
  • Calcitonin Gene-Related Peptide