Off-label use of recombinant activated factor VII in surgical and non-surgical patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comprehensive Canadian review of the off-label use of recombinant activated factor VII in cardiac surgery.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Ketamine anesthesia for pericardial window in a patient with pericardial tamponade and severe COPD.

PURPOSE: To describe the use and concerns of ketamine anesthesia for pericardial window in a patient with pericardial tamponade and severe chronic obstructive pulmonary disease (COPD) with CO(2) retention. CLINICAL FEATURES: A 73-yr-old woman with long-standing COPD and cor pulmonale admitted with pericardial effusion and tamponade had surgery for a pericardial window receiving a total of ketamine 450 mg iv. Arterial pCO(2) increased from 71.8 mmHg preoperatively to 96 mmHg intraoperatively postdrainage of 1000 mL of effusion. Hemodynamic stability and SpO(2) >93% were maintained. Intubation was avoided and concerns of increased pulmonary vascular resistance and potential for right ventricular failure in an already compromised right ventricle were not observed clinically. CONCLUSION: In this patient with pericardial tamponade, COPD and CO(2) retention, the advantages of ketamine included maintaining spontaneous ventilation, avoiding institution and weaning of mechanical ventilation, bronchodilation and relative preservation of the CO(2) response curve. Deleterious effects on right ventricular afterload were not observed.