To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States.Design:
Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol.Setting:
Thirteen U.S.-based emergency departments and ICUs.Patients:
Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included.Interventions:
Procalcitonin was measured daily over the first 5 days.Measurements and Main Results:
The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18–3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.Conclusions:
Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.