Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study

Frank Bloos, John C Marshall, Richard P Dellinger, Jean-Louis Vincent, Guillermo Gutierrez, Emanuel Rivers, Robert A Balk, Pierre-Francois Laterre, Derek C Angus, Konrad Reinhart, Frank M Brunkhorst, Frank Bloos, John C Marshall, Richard P Dellinger, Jean-Louis Vincent, Guillermo Gutierrez, Emanuel Rivers, Robert A Balk, Pierre-Francois Laterre, Derek C Angus, Konrad Reinhart, Frank M Brunkhorst

Abstract

Introduction: The intent of this study was to determine whether serum procalcitonin (PCT) levels are associated with prognosis, measured as organ dysfunctions and 28-day mortality, in patients with severe pneumonia.

Methods: This was a multicenter, observational study of critically ill adult patients with pneumonia requiring mechanical ventilation conducted in 10 academic hospitals in Canada, the United States, and Central Europe. PCT was measured daily for 14 days using an immuno-luminometric assay.

Results: We included 175 patients, 57 with community acquired pneumonia (CAP), 61 with ventilator associated pneumonia (VAP) and 57 with hospital acquired pneumonia (HAP). Initial PCT levels were higher in CAP than VAP patients (median (interquartile range: IQR); 2.4 (0.95 to 15.8) vs. 0.7 (0.3 to 2.15), ng/ml, P < 0.001) but not significantly different to HAP (2.2 (0.4 to 8.0) ng/ml). The 28-day ICU mortality rate for all patients was 18.3% with a median ICU length of stay of 16 days (range 1 to 142 days). PCT levels were higher in non-survivors than in survivors. Initial and maximum PCT levels correlated with maximum Sequential Organ Failure Assessment (SOFA) score r2 = 0.50 (95% CI: 0.38 to 0.61) and r² = 0.57 (0.46 to 0.66), respectively. Receiver operating curve (ROC) analysis on discrimination of 28-day mortality showed areas under the curve (AUC) of 0.74, 0.70, and 0.69 for maximum PCT, initial PCT, and Acute Physiology and Chronic Health Evaluation (APACHE) II score, respectively. The optimal cut-off to predict mortality for initial PCT was 1.1 ng/ml (odds ratio: OD 7.0 (95% CI 2.6 to 25.2)) and that for maximum PCT was 7.8 ng/ml (odds ratio 5.7 (95% CI 2.5 to 13.1)).

Conclusions: PCT is associated with the severity of illness in patients with severe pneumonia and appears to be a prognostic marker of morbidity and mortality comparable to the APACHE II score.

Figures

Figure 1
Figure 1
Time course of procalcitonin levels in patients with pneumonia. Box plot representing the time course of PCT over the two weeks following study inclusion in patients with CAP, HAP, and VAP. * P < 0.05 compared with CAP.
Figure 2
Figure 2
Time course of procalcitonin levels in patients with pneumonia depending on survival. Box plot representing the time course of PCT over the two weeks following study enrolment in survivors and non-survivors. * P < 0.05 compared with survivors.
Figure 3
Figure 3
Initial PCT-values for CAP, HAP, and VAP separated for survivors and non-survivors. *: P < 0.05 (survivors vs. non-survivors), #: P < 0.05 (Bonferroni corrected) compared to VAP.
Figure 4
Figure 4
Correlation of initial or maximum PCT with maximum SOFA-score. Scatter plots representing the initial PCT (panel A) and the maximum PCT (panel B) vs. maximum SOFA score over the two weeks following inclusion. Square of correlation coefficients were r2 = 0.50 (95% CI: 0.38 to -0.61) for initial PCT and r2 = 0.57 (95% CI 0.46 to 0.66) for maximum PCT.
Figure 5
Figure 5
Receiver operator characteristic (ROC) curve for 28-day mortality prediction. Areas under the curve: maximum PCT 0.74 (95% CI: 0.65 to 0.83), initial PCT 0.70 (95% CI: 0.60 to 0.80), and APACHE II 0.69 (95% CI: 0.59 to 0.78).

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