Thursday, September 26, 2013

Kcentra Administration, Revisited

In an earlier post, the nuances associated with the administration of Kcentra was discussed. One point of contingency was associated with the dilution and rate of infusion of Kcentra. The package insert provides the following information with regards to the rate of administration:

"Administer by intravenous infusion at a rate of 0.12 mL/kg/min (approximately 3 units/kg/min) up to a maximum rate of 8.4 mL/min (approximately 210 units/min)."

The package insert also provides additional information with regards to dilution. Rather, it should not be further diluted in any diluent solution and should be given through a separate line.

This leaves us in a bit of a pickle. As the post mentioned, instilling the total volume of Kcentra in an empty evacuated bag may prove to be difficult, especially since they are on shortage and the product is generally needed for immediate administration. In addition, depending on the type of infusion pump available at your institution, one has to account for the tubing volume in which the medication remains in following completion of the infusion. My institution has actually resorted to the use of pediatric syringe pumps for infusion of Kcentra. However, there is a limit on the syringe volume that these syringe pumps can support (most of the time, up to 60 mL), and multiple syringes would have to be drawn up and prepared for infusion of the medication through such pumps.

So what is one to do? You cannot dilute the stuff nor can you give the medication faster than 8.4 mL/min...or can you?

There is still no information available regarding further dilution of Kcentra, which would ease both the reconstitution and administration process. However, I did come across UK transfusion guidelines for Beriplex (same product as Kcentra but goes by a different name in Europe). It recommends for each 500-unit vial of Beriplex/Kcentra is to be reconstituted in 20 mL of diluent that is provided with the product. The recommendation is to draw up the reconstituted 20 mL of product into a syringe and administer as an intravenous injection over 2 to 3 minutes. This makes sense, as you technically would not be exceeding the above recommended infusion rate provided by the manufacturer in the package insert. Granted, if using the maximum 5000-unit dose of Kcentra, this may be quite timely as you would need multiple 20-mL syringes, but it may be a reasonable alternative method for administration without having to go through the efforts of retrieving an evacuated container that may or may not be on shortage or finding and programming a pump that may or may not be flushed with diluent following the infusion.

In addition, I came across a study that looked the effects of the rate of infusion of Beriplex on both safety and efficacy in reversing life-threatening hemorrhage secondary to warfarin. This prospective, international, multicenter study consisted of 43 patients; six of the patients received the product at a rate greater than 10 mL/min, and four of these patients had administration rates that exceeded 15 mL/min, which I found very interesting. What is even more reassuring was that the rate of infusion had no impact on these outcome measures, which demonstrates that in such settings of emergent reversal, administration of 4-factor PCC at rapid rates may be an option.

If only the manufacturer of Kcentra can outright state this to be the case...then we would not be in such a conundrum.