ABSTRACT
PURPOSE: Recombinant factor VIIa (rFVIIa) is being used for refractory, excessive blood loss (EBL) after cardiac surgery, but its safety for this indication is not known. METHODS: The unadjusted and risk-adjusted adverse event (AE) rates were compared between 114 consecutive cardiac surgical patients who received rFVIIa for refractory EBL and 541 concurrent patients who developed EBL but did not receive rFVIIa. Similarly, timing of rFVIIa therapy was assessed by dichotomizing rFVIIa patients based on median number of red blood cell (RBC) units received before therapy. The measured AE was a composite of death, stroke, renal failure, myocardial infarction, and major vein thrombosis. For risk adjustment, logistic regression models for this outcome were constructed using known predictors of AEs. RESULTS: The median RBC units transfused before rFVIIa therapy was eight. The AE rates in the untreated, early (< or = 8 U), and late (> 8 U) treated patients were 24% (129/541), 30% (20/66), and 60% (29/48). The risk-adjustment model included total RBC units, pump time, weaning difficulty, gender, weight, and age. The unadjusted and adjusted AE odds ratios (OR) in the treated vs untreated groups were 2.41 [confidence interval (CI) 1.58-3.67; P < 0.0001] and 1.04 (CI 0.60-1.81; P = 0.9). In the rFVIIa group, the adjusted AE OR was lower in the early treated group (OR 0.41; CI 0.18-0.92; P = 0.03). CONCLUSION: In cardiac surgical patients with refractory hemorrhage, rFVIIa therapy is not associated with increased risk of AEs, and early treatment may be associated with better outcomes.
Subject(s)
Cardiac Surgical Procedures , Factor VII/adverse effects , Hemostatics/adverse effects , Postoperative Hemorrhage/prevention & control , Acute Kidney Injury/etiology , Age Factors , Aged , Body Weight , Cardiopulmonary Bypass , Cause of Death , Erythrocyte Transfusion , Factor VIIa , Female , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Recombinant Proteins/adverse effects , Risk Factors , Safety , Sex Factors , Stroke/etiology , Time Factors , Treatment Outcome , Venous Thrombosis/etiologyABSTRACT
BACKGROUND: Cardiac surgery with cardiopulmonary bypass may result in excessive fibrinolysis and platelet (PLT) dysfunction, resulting in impaired hemostasis and excessive blood loss. Prophylactic use of the antifibrinolytic drugs aprotinin and tranexamic acid is thought to prevent these hemostatic defects. Their relative clinical utility and safety in high-transfusion-risk cardiac surgery, however, is not known. STUDY DESIGN AND METHODS: Using propensity scores, 449 patients who received aprotinin for high-transfusion-risk cardiac surgery were matched to 449 patients who received tranexamic acid from a pool of 10,870 consecutive patients who underwent cardiac surgery at a single center, 586 of whom received aprotinin and the remainder of whom received tranexamic acid. RESULTS: The two matched groups were well balanced in terms of measured perioperative variables. Blood product transfusion rates were similar in the aprotinin and tranexamic acid groups: red blood cells, 79 percent versus 76 percent (p = 0.3); PLTs, 56 percent versus 50 percent (p = 0.06); and plasma, 66 percent versus 61 percent (p = 0.1). Adverse events rates were comparable in the two groups, except for renal dysfunction (defined as a greater than 50% increase in creatinine concentration during the first postoperative week to >100 micromol/L in women and >110 micromol/L in men or a new requirement for dialysis support), which occurred in 24 percent (107/449) of aprotinin patients and 17 percent (75/449) of tranexamic acid patients (p = 0.01). CONCLUSIONS: Aprotinin and tranexamic acid have similar hemostatic effectiveness in high-transfusion-risk cardiac surgery. Within the confines of propensity score matching, our results suggest that aprotinin may be associated with renal dysfunction.
