Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study

Pedro Póvoa, Ignacio Martin-Loeches, Paula Ramirez, Lieuwe D Bos, Mariano Esperatti, Joana Silvestre, Gisela Gili, Gema Goma, Eugenio Berlanga, Mateu Espasa, Elsa Gonçalves, Antoni Torres, Antonio Artigas, Pedro Póvoa, Ignacio Martin-Loeches, Paula Ramirez, Lieuwe D Bos, Mariano Esperatti, Joana Silvestre, Gisela Gili, Gema Goma, Eugenio Berlanga, Mateu Espasa, Elsa Gonçalves, Antoni Torres, Antonio Artigas

Abstract

Background: Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction.

Methods: We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM), for VAP management in 211 patients receiving mechanical ventilation for >72 h. For the present analysis, we assessed all (N = 138) mechanically ventilated patients without an infection at admission. The kinetics of each variable, from day 1 to day 6 of mechanical ventilation, was assessed with each variable's slopes (rate of biomarker change per day), highest level and maximum amplitude of variation (Δ (max)).

Results: A total of 35 patients (25.4 %) developed a VAP and were compared with 70 non-infected controls (50.7 %). We excluded 33 patients (23.9 %) who developed a non-VAP nosocomial infection. Among the studied biomarkers, CRP and CRP ratio showed the best performance in VAP prediction. The slope of CRP change over time (adjusted odds ratio [aOR] 1.624, confidence interval [CI]95% [1.206, 2.189], p = 0.001), the highest CRP ratio concentration (aOR 1.202, CI95% [1.061, 1.363], p = 0.004) and Δ (max) CRP (aOR 1.139, CI95% [1.039, 1.248], p = 0.006), during the first 6 days of mechanical ventilation, were all significantly associated with VAP development. Both PCT and MR-proADM showed a poor predictive performance as well as temperature and white cell count.

Conclusions: Our results suggest that in patients under mechanical ventilation, daily CRP monitoring was useful in VAP prediction. Trial registration NCT02078999.

Keywords: Biomarkers; C-reactive protein; Clinical Pulmonary Infection Score; Diagnosis; Mid-region fragment of pro-adrenomedullin; Prediction; Procalcitonin; Ventilator-associated pneumonia.

Figures

Fig. 1
Fig. 1
Flowchart of patients undergoing mechanical ventilation during the study period
Fig. 2
Fig. 2
Time course of biomarkers (CRP, PCT and MR-proADM), temperature and WCC from day 1 to day 6 of mechanical ventilation in ventilator-associated pneumonia (VAP) patients and non-infected controls (a CRP, b CRP ratio, c PCT, d MR-proADM, e WCC, f temperature). Time-dependent analysis of CRP, CRP ratio and CPIS was significantly different between VAP patients and controls (p < 0.001, p < 0.001 and p = 0.019, respectively). Some variables, namely CRP and CRP ratio, became significantly higher by day 5 in patients that will develop a VAP in comparison with controls (*p < 0.05). CRP C-reactive protein, MR-proADM mid-region fragment of pro-adrenomedullin, PCT procalcitonin, VAP ventilator-associated pneumonia, WCC white cell count
Fig. 3
Fig. 3
Curve of disease risk probability of ventilator-associated pneumonia (VAP), for the possible range of kinetics of CRP concentration changes over time, assessed by the slope, highest value and Δmax from day 1 to day 6 of mechanical ventilation (a–c CRP, d–f PCT, respectively). Ideally, the line should show a linear relationship between the marker and the probability of VAP. For PCT, the same calibration plots are presented (slope, highest and Δmax). CRP C-reactive protein, VAP ventilator-associated pneumonia

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