Evaluating the use of recombinant human activated protein C in adult severe sepsis

Abstract

The Surviving Sepsis Campaign developed guidelines for the administration of recombinant human activated protein C in adult severe sepsis. However, it is not clear how these impacted clinical practice or patient outcome. The Surviving Sepsis Campaign has developed an extensive database to assess the efficacy of the overall effect of its guidelines on clinical practice and patient outcome. From data submitted to the Surviving Sepsis Campaign database from January 2005 through March 2008, we evaluated data regarding the administration of recombinant human activated protein C in adult severe sepsis. Data from 15,022 subjects at 165 sites were analyzed. Of patients with severe sepsis in the database, 1,009 of 15,022 (8%) received recombinant human activated protein C. Recombinant human activated protein C was administered within 24 hrs of the onset of sepsis in 76% (771 of 1009) of patients. Patients in North America (7.1%) and Europe (6.8%) were more likely to receive recombinant human activated protein C than patients in South America (4.2%, p<.001). After adjusting for covariates, the group that received recombinant human activated protein C had a significantly reduced associated hospital mortality (odds ratio 0.76, 95% confidence interval 0.66-0.86, p<.001). Comparing all the patients who received recombinant human activated protein C to those who did not receive recombinant human activated protein C, the reduction in the adjusted hospital mortality was only statistically significant in patients who had multiorgan dysfunction (odds ratio 0.82, 95% confidence interval 0.69-0.98, p=.027) vs. those who only had single organ dysfunction (odds ratio 0.78, 95% confidence interval 0.59-1.02, p=.072). However, in patients who received recombinant human activated protein C before 24 hrs there was a reduction in adjusted hospital mortality in patients with only one organ dysfunction (odds ratio 0.70, 95% confidence interval 0.51-0.9, p=.03) as well as patients with multiorgan dysfunction (odds ratio 0.78, 95% confidence interval 0.64-0.94 p=.012). There was a statistically significant increase over time in the percentage compliance with the institution of a recombinant human activated protein C administration policy from the first, second, and eighth quarters (47.4%, 46.2%, and 60.7%, respectively) (p<.001). There was also a statistically significant increase in the actual administration rates of recombinant human activated protein C over the same timeline (p<.001), with administration rates of recombinant human activated protein C reaching 9.2% in the last quarter. Recombinant human activated protein C use was associated with a significant improvement in hospital mortality in patients who participated in the Surviving Sepsis Campaign.