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ANSWER TO QUIZ OF THE WEEK: April 1, 2005

1. Ideally, stop the drug infusion 1 - 2 hours prior to chest tube insertion. If respiratory instability does not allow this period of time, clinical judgement needs to be used. Insert the chest tube as urgently as needed according to the patient's condition.

Drotrecogin alfa activated (Xigris) is activated Protein C. Our own endogenous Protein C is converted to activated Protein C on intact endothelial cell surfaces, in response to the production of thrombin. Activation of Protein C decreases the production of proinflammatory cytokines (antiinflammatory properties), deactivates co-factors XIIIa and Va to decrease further thrombin production (anticoagulant properties) and opposes antifibrinolytic factors (promoting fibrinoolysis). Activated protein C is an important endogenous factor that helps maintain homeostasis.

In sepsis, endogenous levels of Protein C decrease and endothelial cell injury reduces the ability to convert available Protein C to the activated form. Deficiency of activated Protein C prolongs the inflammatory, coaguation and antifibrinolytic response.

The most important risk during administration of Xigris is bleeding. The half-life of Xigris is 13 minutes. During the PROWESS trial, Xigris was stopped 1 hour prior to a minor procedure (e.g., line insertion, chest tube insertion) and 2 hours before major procedures (e.g., general surgery). The drug was resumed 1 hour following completion of minor procedures and 12 hours post major procedures. The drug monograph recommends stopping Xigris 2 hours before any procedure, however, this may not be possible. You cannot wait 1 or 2 hours for chest tube insertion with a tension pneumothorax. Stop the drug immediately, insert the chest tube as needed and monitor for bleeding. FFP may be administered if needed.

2. Restart the infusion 1 hour following chest tube insertion. The orginal 96 hour infusion should have ended Friday at 1200 hours. Adjust the stop time to ensure 96 hours of drug infusion (e.g., if the drug was off for 2 hours, continue the infusion until 1400 hrs). Be sure to notify pharmacy of any infusion adjustments.

References:

Bernard, G. et al. (2001). Efficacy and safety of recombinant human activated protein C for severe sepsis. NEJM, 344, 699-709.

Vincent, J. et al. (2003). Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial*. Crit Care Med. 31(3); 834-840.

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