Low-dose, off-label drotrecogin alfa (xigris) in severe sepsis

In this article, we describe a successful low-dose, off-label usage of drotrecogin alfa (Xigris), given at 18 mcg/kg per hour, in a patient with severe sepsis who had an Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 26 and multiorgan failure.

A 64-year-old man was admitted to the surgical intensive-care unit of Winthrop University Hospital in Mineola, New York. After undergoing small-bowel resection secondary to obstruction, he became severely septic. Because of his high risk of death (with an APACHE II score of 26 and two organ failures), he was initially treated with drotrecogin alfa 24 mcg/kg per hour, the dose approved by the U.S. Food and Drug Administration (FDA). Within four hours, his activated partial thromboplastin time became significantly prolonged from a baseline of 27.8 to 92.9 seconds, and he had coffee-ground nasogastric tube output. In light of signs of bleeding, drotrecogin alfa was temporarily discontinued. After 26 hours without further evidence of bleeding, drotrecogin alfa was administered at a lower dose of 18 mcg/kg per hour. The manufacturer's recommendation of 96 hours of infusion therapy was completed with the lower dosing. The patient's condition improved significantly, and eventually he was discharged home.

This case report demonstrates an alternative use of drotrecogin alfa at a lower dose of 18 mcg/kg per hour in a severely septic patient who could not tolerate the FDA-approved dose of 24 mcg/kg per hour because of bleeding.