Long Pentraxin 3 as a Predictive Marker of Mortality in Severe Septic Patients Who Received Successful Early Goal-Directed Therapy

Abstract

Purpose: Pentraxin 3 (PTX3) has been suggested to be a prognostic marker of mortality in severe sepsis. Currently, there are limited data on biomarkers including PTX3 that can be used to predict mortality in severe sepsis patients who have undergone successful initial resuscitation through early goal-directed therapy (EGDT).

Materials and methods: A prospective cohort study was conducted among 83 severe sepsis patients with fulfillment of all EGDT components and the achievement of final goal. Plasma PTX3 levels were measured by sandwich ELISA on hospital day (HD) 0, 3, and 7. The data for procalcitonin, C-reactive protein and delta neutrophil index were collected by electric medical record. The primary outcome was 28-day all-cause mortality.

Results: 28-day all-cause mortality was 19.3% and the median (interquartile range) APHCH II score of total patients was 16 (13-19). The non-survivors (n=16) had significantly higher PTX3 level at HD 0 [201.4 (56.9-268.6) ng/mL vs. 36.5 (13.7-145.3) ng/mL, p=0.008]. PTX3 had largest AUC(ROC) value for the prediction of mortality among PTX3, procalcitonin, delta neutrophil index, CRP and APACHE II/SOFA sore at HD 0 [0.819, 95% confidence interval (CI) 0.677-0.961, p=0.008]. The most valid cut-off level of PTX3 at HD 0 was 140.28 ng/mL (sensitivity 66.7%, specificity 73.8%). The PTX3 and procalcitonin at HD 0 showed strong correlation (r=0.675, p<0.001). However, PTX3 at HD 0 was the only independent predictive marker in Cox's proportional hazards model (≥140 ng/mL; hazard rate 7.16, 95% CI 2.46-15.85, p=0.001).

Conclusion: PTX3 at HD 0 could be a powerful predictive biomarker of 28-day all-cause mortality in severe septic patients who have undergone successful EGDT.

Keywords: Pentraxin 3; early-goal directed therapy; mortality; predictive biomarker; severe sepsis.

Fig. 1. The flow chart on the enrollment processes for study participants. ^*This was defined as the fulfillment of all EGDT components and achievement of the final goal of superior vena cava oxygen saturation ≥70% within 6 hrs after arrival at the emergency department, as well as faithfully implemented EGDT and initial resuscitation of Surviving Sepsis Campaign international guidelines for management of severe sepsis and septic shock according to the recent update version at enrollment. EGDT, early goal-directed therapy.

Fig. 2. Changing pattern of PTX3 levels at HD 0, 3, and 7 in survivors and non-survivors. The middle and upper/lower error bars mean the median and interquartile ranges, respectively. PTX3, pentraxin 3; HD, hospital day.

Fig. 3. Comparison of ROC curves for inflammatory markers (A) and APACH II/SOFA score (B) measured at hospital day 0 for the prediction of 28-day all-cause mortality. PTX3, delta neutrophil index, CRP and procalcitonin were measured at hospital day 0 within 24 hrs of arrival at the emergency department. SOFA score was assessed upon arrival at the emergency department and APACHE II score was assessed based on the worst values over the first 24 hrs of intensive care unit care. ROC, receiver operating characteristic; AUC, area under the ROC curve; CI, confidential interval; PTX3, pentraxin 3; PCT, procalcitonin; CRP, C-reactive protein; DNI, delta neutrophil index; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment.

Fig. 4. Kaplan-Meier survival curve according to PTX3 level on hospital day 0 with a cut-off point of 140 ng/mL (A) and comparison of short-term change in PTX3 level between hospital day 0 and 3 in both survivors and non-survivors (B). PTX3, pentraxin 3; HD, hospital day.