SEATTLE — When it comes to initiating therapy with drotrecogin alfa in patients with severe sepsis, the earlier the better.
That's the key message from a large study of patients who received drotrecogin alfa (Xigris) at 139 hospitals in the United States between November 2001 and June 2003, Frank Ernst, Pharm. D., reported at the annual meeting of the American College of Chest Physicians.
Drotrecogin alfa (activated) is recombinant human activated protein C; it mimics endogenous protein C, which inhibits coagulation and inflammation when activated.
Waiting 2 or more days to initiate the drug predicted hospital mortality, whereas earlier initiation predicted lower hospital costs and shorter lengths of stay among survivors, reported Mr. Ernst, a pharmacist at Eli Lilly and Co., Indianapolis.
In a study funded by Lilly, Mr. Ernst and his associates studied database records of 1,179 patients who received drotrecogin alfa during their hospital stay following evident severe sepsis, defined as concurrent antibiotic use plus ventilator and/or vasopressor use. The records were obtained from a large national database of hospital discharge records maintained by Solucient, a health information technology company.
Of the 1,179 patients, 509 received drotrecogin alfa on the same day that they had evident severe sepsis (same-day patients), 354 received the drug the day after they had evident severe sepsis (next-day patients), and 323 received the drug 2 days or more after they had evident severe sepsis (day 2-plus patients).
At ICU admission, day 2-plus patients had fewer organ dysfunctions than did patients in the other two groups. But between ICU admission and initiation of drotrecogin alfa, organ dysfunctions increased significantly more among day 2-plus patients than did next-day and same-day patients.
Hospital mortality was predicted by ventilator use (odds ratio [OR] 5.1), vasopressor use (OR 2.6), and initiation of drotrecogin alfa on day-2 plus (OR 1.7).
Among survivors, 7% shorter length of stay and 10% lower adjusted post-drotrecogin alfa administration costs were predicted by same-day or next-day initiation.
Limitations of the study were its retrospective design and the fact that the database used contained limited clinical information, Mr. Ernst noted.