Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.
ABSTRACT Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.
Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.
The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).
Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.
- SourceAvailable from: Donald F Brophy[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND:Hemorrhage and coagulopathy are associated with morbidity and mortality in critically ill patients. Recombinant activated factor VII (rFVIIa) is frequently used in these situations to control bleeding; however, few controlled clinical trials have demonstrated clinical benefit and prolonged survival.OBJECTIVE:To compare clinical outcomes and thromboembolic events in intensive care unit (ICU) patients who received rFVIIa versus ICU patients who did not between 2000 and 2005.METHODS:A total of 2918 nonhemophiliac adult ICU patients, which included 1459 who received at least 1 dose of rFVIIa and 1459 matched controls who did not, were included in a retrospective database study. Data were extracted from the Solucient ACTracker database, which included 550 hospitals across the US. Measures included patient demographics, rFVIIa prescribing, death, thromboembolic events, dis charge disposition, length of stay, and transfusion data.RESULTS:The most common primary diagnoses for patients receiving rFVIIa included traumatic brain injury, cirrhosis, and nontraumatic intracranial hemorrhage. Patients receiving rFVIIa were more likely to have comorbidities, including mechanical ventilation, acute kidney injury, sepsis, hemodialysis, and gastro intestinal bleeding (p < 0.0001). The average rFVIIa dose was 4.8 mg and 82% of patients received 1 dose. Compared to controls, patients receiving rFVIIa had greater odds of death (OR 2.1, 95% CI 1.8-2.6, p < 0.0001), transfusion (OR 2.1, 95% CI 1.8-2.5, p < 0.0001), and longer length of stay (p < 0.001). There was no significant difference in thromboembolic events between groups.CONCLUSIONS:While we cannot show direct causality between rFVIIa and the poor clinical outcomes documented in ICU patients, they provide important insight for critical care clinicians.Annals of Pharmacotherapy 03/2013; · 2.57 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient's tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.European Journal of Anaesthesiology 06/2013; 30(6):270-382. · 2.79 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Recombinant activated factor VII (rFVIIa) is often used in off-label indications, including many situations in which the patients are at risk of thrombosis. In this study, we retrospectively reviewed the use of rFVIIa in patients with acute liver failure - UNOS Status 1A (ALF-1A) to determine its efficacy and safety profile. Using the transplantation records, all adult patients with ALF-1A were identified from 6/2001 to 3/2009. From patients' medical charts, rFVIIa dose, blood component usage, short-term outcomes [length of intensive care unit (ICU) and hospital stay, ability to undergo orthotopic liver transplant (OLT) and in-hospital survival rate] and adverse events were examined. Forty-two patients with ALF-1A were identified. Fifteen patients received rFVIIa with doses ranging between 24·4 μg/kg and 126·8 μg/kg. Three patients received two doses of rFVIIa. The age, baseline activated partial thromboplastin time (aPTT) and platelet (PLT) count were not statistically different between the group receiving rFVIIa versus the group that did not. However, the prothrombin time (PT) was significantly higher in the rFVIIa group. Although the rFVIIa group stayed in the ICU longer and required significant more blood products during admission, there was no statistical difference between the two groups in terms of length of hospital stay, ability to undergo OLT and survival rate. There was no increase in complications, including thrombosis, after receiving rFVIIa. Recombinant activated factor VII (rFVIIa) appears to be safe in patients with ALF-1A, but to elucidate its full role, a randomized controlled trial would be ideal.Vox Sanguinis 07/2013; · 2.85 Impact Factor