Variable efficacy of drotrecogin alfa (activated) in severe sepsis and septic shock: a meta-analysis

In this meta-analysis, we aimed to assess the clinical efficacy of drotrecogin alfa (activated) (DAA) in severe sepsis and septic shock. A literature search on PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrails.gov until February 10, 2017 was used to identify the relevant randomized controlled trials. Data analysis was performed using Stata 14.0. Six eligible studies were included in this study. With respect to the 28-day all-cause mortality, DAA had no significant effect (relative risk (RR)=1.01, 95% confidence interval (95% CI): 0.85-1.2, I2=70.1%, P=0.005). In addition, DAA showed no significant difference in the 90-day all-cause mortality (RR=1.09, 95% CI: 0.99-1.2, I2=23.4%, P=0.271). DAA was also associated with an increased risk of serious bleeding (RR=1.43, 95% CI: 1.03-1.98, I2=0.00%, P=0.606). Moreover, the pooled results of intracranial hemorrhage events showed no statistical significance (Peto odds ratio =1.21, 95% CI: 0.50-2.9, I2=0.00%, P=0.897). No publication bias was observed for any of the outcomes, as evidenced by the symmetry of the funnel plots and Egger’s test. Based on these results, DAA should be used carefully in the treatment of severe sepsis and septic shock in adults.