Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

Abstract

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation.

Methods: suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obtained on the day of inhalation trauma and on alternate days thereafter until patients were completely weaned from the mechanical ventilator. Mechanically ventilated patients without burns and without pulmonary disease served as controls.

Results: Systemic levels of suPAR in burn patients with inhalation trauma were not different from those in control patients. On admission and follow up, pulmonary levels of suPAR in patients with inhalation trauma were significantly higher compared with controls. Pulmonary levels of suPAR highly correlated with pulmonary levels of interleukin 6, a marker of inflammation, and thrombin-antithrombin complexes, markers of coagulation, but not plasminogen activator activity, a marker of fibrinolysis. Systemic levels of suPAR were predictive of the duration of mechanical ventilation and length of intensive care unit (ICU) stay. Duration of mechanical ventilation and length of ICU stay were significantly longer in burn-injury patients with systemic suPAR levels > 9.5 ng/ml.

Conclusions: Pulmonary levels of suPAR are elevated in burn patients with inhalation trauma, and they correlate with pulmonary inflammation and coagulation. Although pulmonary levels of suPAR may have diagnostic value in burn-injury patients, systemic levels of suPAR have prognostic value.

Figure 1

Systemic and pulmonary levels of soluble urokinase-type plasminogen activator receptor (suPAR). (a) Box plots of systemic levels of suPAR; systemic levels of suPAR do not significantly differ from levels in control patients on admission and on days 3 and 5 after admission. (b) Box plots of pulmonary levels of suPAR; compared with those in control patients, pulmonary levels of suPAR are significantly higher in burn-injury patients on admission and on days 3 and 5 after admission. Boxes represent the interquartile ranges. Outliers are excluded from the figure. N, number of patients per group per time point. The P values indicate statistical significance.

Figure 2

Prediction of inhalation trauma. Receiver operating characteristic (ROC) curve comparing the ability of (a) systemic and (b) pulmonary levels of suPAR to discriminate between the presence or absence of inhalation trauma in mechanically ventilated patients by using a cut-off value of 6.1 ng/ml. The AUC, the P value, the sensitivity, and the specificity are given in each panel.

Figure 3

Correlations between levels of soluble urokinase-type plasminogen activator receptor (suPAR) and inflammation. Analyses of the correlation between systemic interleukin 6 (IL-6) levels and systemic levels of suPAR in (a) burn-injury patients and (b) control patients, and pulmonary IL-6 levels and pulmonary levels of suPAR in (c) burn-injury patients and (d) control patients. Linear correlations with 95% confidence intervals are shown. Pearson correlation coefficients (r) and P values are given in each panel.

Figure 4

Correlations between levels of soluble urokinase-type plasminogen activator receptor (suPAR) and coagulopathy. Analyses of the correlation between pulmonary levels of suPAR and parameters of (a) pulmonary coagulation and (b) fibrinolysis. Linear correlations with 95% confidence intervals are shown. Pearson correlation coefficients (r) and P values are given in each panel.

Figure 5

Prognostic value of soluble urokinase-type plasminogen activator receptor (suPAR). Analyses of the correlation between pulmonary levels of suPAR in burn-injury patients with inhalation trauma and (a) duration of mechanical ventilation and (b) length of ICU stay, and systemic levels of suPAR and (c) duration of mechanical ventilation and (d) length of stay in the ICU. Linear correlations with 95% confidence intervals are shown. Pearson correlation coefficients (r) and P values are given in each panel.

Figure 6

Prognostic value of soluble urokinase-type plasminogen activator receptor (suPAR). Box plot of (a) duration of mechanical ventilation and (b) length of stay in the ICU of burn-injury patients with inhalation trauma. Boxes represent the interquartile ranges. N, number of patients per group. Kaplan-Meier curves showing the rate of freedom from (c) mechanical ventilation and (d) ICU stay in burn-injury patients with systemic suPAR < 9.5 ng/ml and > 9.5 ng/ml. P values are given in each panel.