[Show abstract][Hide abstract] ABSTRACT: Purpose:
Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients.
For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events.
One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events.
The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.
Canadian Journal of Anaesthesia 06/2014; 61(8). DOI:10.1007/s12630-014-0184-z · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the present study was to identify and determine the prognostic importance of such risk factors.
Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration.
AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.
[Show abstract][Hide abstract] ABSTRACT: This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk.
At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy.
In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.
[Show abstract][Hide abstract] ABSTRACT: In cardiac surgery, excessive blood loss requiring large-volume red blood cell (RBC) transfusion is a common occurrence that is associated with significant morbidity and mortality. The objectives of this study were to measure the interinstitution variation and predictability of large-volume RBC transfusion.
Data were retrospectively collected on 3500 consecutive cardiac surgical patients at seven Canadian hospitals during 2004. The crude and risk-adjusted institutional odds ratios (ORs) for large-volume (>or=5 U) RBC transfusion were calculated with logistic regression. The predictive accuracy of an existing prediction rule for large-volume RBC transfusion was calculated for each institution.
Large-volume RBC transfusion occurred in 538 (15%) patients. When compared to the reference hospital (median crude rate), the institutional unadjusted and adjusted ORs for large-volume RBC transfusion ranged from 0.29 to 1.26 and 0.14 to 1.15, respectively (p<0.0001 for interinstitution variation). The variation was lower, but still considerable, for excessive blood loss, defined as at least 5-U RBC transfusion or reexploration; the ORs ranged from 0.42 to 1.22 (p<0.0001). The prediction rule performed well at most sites; its pooled positive predictive value for excessive blood loss was 71 percent (range, 63%-89%), and its negative predictive value was 90 percent (range, 87%-93%).
There is marked interinstitution variation in large-volume RBC transfusion in cardiac surgery that is not explained by patient- or surgery-related factors. Despite this variation, patients at high or low risk for large-volume RBC transfusion can be accurately identified by a prediction rule composed of readily available clinical variables.