Predicting response to recombinant activated factor VIIa administration in the critically ill

Introduction

There is considerable interest in the potential use of recombinant activated factor VIIa (rFVIIa) as adjunctive therapy in major haemorrhage; to date, however, only a single RCT supports its use as rescue treatment [1]. Previous efforts have been made to establish which patients are most likely to benefit from rFVIIa using scoring systems, but the optimal circumstances remain unclear [2, 3]. The purpose of this study was to investigate potential factors influencing response to rFVIIa (in terms of subsequent packed red cell (PRBC) transfusion) and survival in a cohort of nonhaemophiliac patients treated with rFVIIa for haemorrhage in our region.

Methods

We performed a retrospective analysis of the records of 40 nonhaemophiliac critically ill adults treated at seven hospitals in the Cheshire and Mersey region with rFVIIa for haemorrhage resistant to conventional management. The influence of potential factors on post-rFVIIa PRBC transfusion and ICU survival were evaluated using the Mann–Whitney U test and Fisher's exact test, respectively.

Results

The 40 patients were surgical (21 patients), trauma (11 patients), obstetric (three patients), cardiothoracic (three patients) and medical (two patients). The median age was 53.5 years, 26 patients were male. A median single dose of 90 μg/kg rFVIIa was administered after a median 14.5 units PRBC. Fifty-three per cent of patients survived to ICU discharge. Factors influencing PRBC transfusion in the 24 hours post rFVIIa administration and ICU survival are presented in Tables 1 and 2.

Table 1 Median post-rFVIIa PRBC transfusion in the presence or absence of factor

Table 2 Survival in the presence or absence of factor

Conclusion

While the optimal circumstances for rFVIIa administration remain unclear, it seems easier to focus on the question 'Who is unlikely to benefit?' pH ≤ 7.1 at the time of administration of rFVIIa was associated with significantly increased PRBC transfusion and 100% mortality. Hypothermia (temperature ≤ 35°C) and cardiac arrest prior to rFVIIa administration were also associated with significantly increased PRBC transfusion. Although there have been previous reports of survival following rFVIIa administration for haemorrhage in the presence of pH < 7.1, such profound acidaemia provides a strong indication that rFVIIa is likely to be futile.