Einfluss einer Statin-Therapie auf das Überleben von Patienten mit Sepsis-assoziiertem ARDS

Abstract

The acute respiratory distress syndrome (ARDS) was first described in 1967. Even though therapy has improved over the years, its mortality remains high, especially if it is associated to a sepsis. The syndrome consists of an overwhelming inflammation due to a previous direct or indirect damage to the lung tissue. The inflammation leads to alveolar damage accompanied by an infiltration of protein-rich pulmonary-edema fluid in the alveolar space, leading to respiratory failure. Despite the pulmonary failure, a persistance of the inflammation can also result in extra- pulmonary organ failure, cellular damage or death. Statins, a frequently prescribed medication for treatment of hypercholesterolemia, may also attenuate inflammation due to their immunosuppressive attributes and thus may have a positive impact on the outcome and the clinical course of patients with ARDS. The aim of this study was to examine a potential benefit of a prior statin therapy on the survival of patients with sepsis-associated ARDS. Therefore patients were screened daily in three intensive care units (ICUs) at the University Medical Center of Goettingen to determine if they would match the criteria for sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM). If positive, the patients were furthermore evaluated according to the Berlin definition of ARDS (dividing ARDS into a mild, moderate and severe form), to identify those with sepsis-associated ARDS. All included patients were checked for previous medication and followed on, up to a maximum of 28 days after the onset of sepsis. If they had prior statin therapy, medication was continued on the ICU. The organ function was assessed at baseline using the Sequential Organ Failure Assessment-score (SOFA-score) and daily reassessed over the next 28 days. During their follow-up, the primary outcome variable of this examination was mortality. Out of 7673 screened patients, 404 who developed sepsis- associated ARDS were enrolled in this study. Of these, a total of 27% had prior statin therapy. Exclusively in the patients with severe ARDS an improved 28-day survival could be examined (P = 0.0193). After carrying a propensity score-matching, the improved 28-day survival among patients with statin-therapy could be confirmed (P = 0.0205). The performed Cox regression analysis to exclude confounders supported the significance of statin therapy as a covariate for mortality (hazard ratio, 5.46; P = 0.0156). In conclusion, the study suggests that a prior statin therapy may have a beneficial effect on patients with sepsis-associated ARDS. Despite the primary outcome variable, also several secondary variables (such as organ function) also showed improved results in the statin therapy cohort.