Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis

Background: The early diagnosis of sepsis plays a central role in patient management. Many mediators to be the cause of sepsis have been proposed. In the present study the combined measurement of procalcitonin (PCT) and mid-regional pro-adrenomedullin (MR-proADM) and their appropriate cut-off values in sepsis patients were evaluated. Methods: PCT and MR-proADM were measured with commercially available immunoluminometric assays (Brahms, Hennigsdorf, Germany) in 200 septic patients, 90 patients with SIRS and 30 healthy individuals. Data were analyzed with ROC curve analysis and likelihood ratios with the MedCalc 11.6.1.0 package. Results: Healthy controls and non-infectious SIRS were clearly distinguished from sepsis patients using the follow ing cut-off values: 0.30 ng/mL for PCT and 1 nmol/L for ADM. In the 200 septic patients the areas under the curve (AUCs) for PCT and MR-proADM were 0.921 and 0.977, respectively, with a statistically significant difference between the two areas of 0.0563 (p = 0.0002). Gram-positive, Gram-negative, yeast and polymicrobial sepsis patients showed different geometric means of the two biomarkers: this difference was relevant in Gram-positive sepsis and in yeast sepsis, 0.0819 (p = 0.0076) and 0.188 (p = 0.0062), respectively. The combined use of PCT and MR-proADM gave a post-test probability of 0.998 in the cohort of all septic patients. By test combination the post-test probability changed from 0.803 to 0.957 in Gram-positive sepsis and from 0.928 to 0.995 in yeast sepsis. Conclusions: In conclusion, data from this study demonstrates that the combined use of PCT and MR-proADM, may substantially improve the early diagnosis of sepsis.