A Sustained Reduction in Serum Cholinesterase Enzyme Activity Predicts Patient Outcome following Sepsis

Figure 1. A sustained reduction in BChE enzyme activity identifies 90-day nonsurvivors following sepsis. BChE (a–d), CRP (e, f), and WBCC (g, h) measurements obtained from patient blood samples taken at the time point of the sepsis detection (0) and 1, 2, 7, 14, and 28 days later in patients surviving 90 days (open circles) and in nonsurvivors (closed circles). BChE enzyme activity is plotted as a raw value (a) and normalized to day 0 (initial value, c). Magnified time lines (b, d, f, h) show the measurements obtained during the first two days following sepsis detection. Dark gray-shaded areas indicate time periods where the statistical significance between the two patient groups occurs (p < 0.01, Mann–Whitney U test). Data are medians. BChE: butyrylcholinesterase; CRP: C-reactive protein; WBCC: white blood cell count.

Figure 2. Activity pattern of the inflammatory biomarkers in patients with sepsis. Activity of PCT (a, b), MR-proADM (c, d), IL-6 (e, f), and TNF-α (g, h) was measured at the time point of sepsis detection (0) as well as 1, 2, 7, 14, 21, and 28 days later in patients who survived (open circles) and in those who died within 90 days (closed circles). Magnified time lines (b, d, f, h) represent measurements obtained within the first two days after the sepsis detection. Dark gray-shaded areas indicate time periods with the statistical difference between the patient groups (p < 0.05, Mann–Whitney U test). Data points are medians. PCT: procalcitonin; MR-proADM: midrange proadrenomedullin; IL-6: interleukin 6; TNF-α: tumor necrosis factor alpha.

Figure 3. Measured BChE enzyme activity predicts the patient outcome following sepsis. (a) Kaplan–Meier curve shows the survival analysis of septic patients included in this study. (b) ROC curve analysis for the BChE activity measured at the time point of the clinical detection of sepsis revealed an AUC of 0.7 with the optimal cutoff value of 1.661 × 103 U/L (CI 0.5–0.8, 94% sensitivity, 48% specificity). (c) A comparison of the Kaplan–Meier curves stratified according to the cutoff value for the measured BChE enzyme activity, as shown in (b). BChE: butyrylcholinesterase; ROC: receiver operating characteristic; AUC: area under the curve; CI: confidence interval; c.o.v.: cutoff value.

Figure 4. Disease severity scores predict outcome in patients with sepsis. APACHE II (a, b), SOFA (c, d), and SAPS II (e, f) scores were calculated from patients surviving sepsis (open circles) and from those who did not survive 90 days following sepsis detection (closed circles). Disease severity scores were obtained at the time point of the sepsis diagnosis and repeated 1, 2, 7, 14, 21, and 28 days later. Magnified time lines (b, d, f) show the disease severity scores obtained within the first two days following sepsis detection. Dark gray-shaded areas indicate the time points where the statistical significance could be observed (p < 0.05 for APACHE II, p < 0.01 for SOFA, and p < 0.001 for SAPS II; Mann–Whitney U test). Data points are medians. APACHE II: Acute Physiology and Chronic Health; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score.