Off-label use of recombinant activated factor VII in intractable haemorrhage after cardiovascular surgery: an observational study of practices in 23 French cardiac centres (2005-7).
The study aimed to describe French off-label use of rFVIIa for intractable bleeding in major cardiovascular surgery. Retrospective observational analysis of data from 2005 to October 2007 (no formal guidelines were available) was employed. The collect request form was elaborated by a multidisciplinary committee. Data on 109 patients--37 mechanical cardiac assist devices--were collected, with repeated injection for 24%. Bleeding stopped, decreased or continued in 43%, 37% and 20% of the cases, respectively. For patients treated in the intensive care unit (ICU), hourly bleeding decreased from 365 ± 212 to 115 ± 106 ml h(-1) (p<0.001). The median number of transfused products was 25 (2-90) before and 6 (0-48) after rFVIIa (p<0.001). Most patients had been well compensated with fibrinogen (>1g.l(-1)) and platelets (>50 G.l(-1)) before rFVIIa. The bleeding outcome (cessation, decrease or no change) was associated with the infused dose (81 ± 31, 71 ± 24, 64 ± 23 μg.kg(-1); p = 0.044) and did not differ whether rFVIIa was administered in the operating room (49%) or ICU (51%). Thrombotic events occurred in 13% of patients without assist devices and in 27% of those with them (but without obvious intra-device clotting). The overall 28-day survival rate was 60% and associated with bleeding outcome (p = 0.002). rFVIIa rescue therapy was followed by control of bleeding in a substantial number of the patients with seemingly acceptable safety; however, thrombotic risk remains a matter of concern. Our observational study suggests that the dose to be tested prospectively is at least 80 μg.kg(-1).