Detection of Acute Phase Response and Infection. The Role of Procalcitonin and C-Reactive Protein

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Abstract
Established parameters, e.g. C-reactive protein (CRP), do not differentiate specifically enough between patients developing an infection and those exhibiting an acute phase response following cardiac surgery. The objective of this prospective study was to investigate if procalcitonin (PCT) is more helpful than CRP. During a 1-year period, seven out of 563 patients (1.2%) developed systemic infections (group A) after cardiac operations with cardiopulmonary bypass (CPB), and additional eight patients (1.4%) had local wound infections requiring surgical therapy (group B). Blood samples for PCT and CRP measurements were taken preoperatively, at the onset of infection (d1), as well as on the third day (d3), fifth day (d5), and seventh day (d7) following diagnosis of infection. Forty-four randomly selected patients undergoing cardiac surgery with CPB without clinical signs of infection, additional intensive care unit (ICU) management or additional antibiotic treatment served as control (group C) to assess the PCT and CRP contribution to acute phase response. PCT and CRP levels were measured preoperatively, on the first (d1), third (d3) and fifth day (d5) after operation. At the onset of infection, PCT levels (median interquartile range 25%-75%) increased significantly in group A as compared to baseline values (10.86 (3.28-15.13) ng/ml vs. 0.12 (0.08-0.21) ng/ml), and decreased during treatment to still significantly elevated values on d5 (0.56 (0.51-0.85) ng/ml). CRP levels were significantly elevated on all days investigated with no trend towards normalisation (d1: 164.5 (137-223) mg/l) vs. 1.95 (1.1-2.8) mg/l preoperatively, d5: 181.1 (134-189.6) mg/l. In group B, no increase in PCT levels, but a significant increase of CRP from d1 (165.9 (96.6-181.6) mg/l) vs. 3.7 (2-4.3) mg/l preoperatively) until d5 98 (92.8-226.2) mg/l was detected. In group C, postoperative PCT levels increased slightly but significantly in the absence of infection on d1 (0.46 (0.26-0.77) ng/ml vs. 0.13 (0.08-0.19) ng/ml preoperatively), and d3 (0.37 (0.2-0.65) ng/ml and reached baseline on d5 (0.24 (0.11-0.51) ng/ml)). CRP levels were significantly elevated as compared to baseline on all postoperative days investigated (baseline: 1.75 (0.6-2.9) mg/l, d1: 97.5 (74.5-120) mg/l), d3: 114 (83.05-168.5) mg/l, d5: 51.4 (27.4-99.8) mg/l)). PCT showed a significant correlation to CRP in group A (r =0.48, p < 0.001), a weak correlation in group C (r=0.27, p=0.002) and no correlation in group B. Intergroup comparison revealed a significant difference for PCT between all groups (A>C>B) and significantly higher CRP levels in group A vs. C and in group B vs. C. Thus, the pattern high PCT/high CRP appears to indicate a systemic infection, while low PCT/high CRP indicates either acute phase response or local wound problems, but no systemic infection. The cost for PCT measurements was 5.6-fold higher as compared to CRP. Due to the significant differences in the degree of increase, PCT appears to be useful in discriminating between acute phase response following cardiac surgery with CPB or local problems and systemic infections, with additional CRP-measurement increasing the specificity.