Anesthesiology 2005; 102:269 –75 © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Recombinant Coagulation Factor VIIa in Major Liver Resection A Randomized, Placebo-controlled, Double-blind Clinical Trial J. Peter A. Lodge, M.D., F.R.C.S.,* Sven Jonas, M.D.,† Elie Oussoultzoglou, M.D.,‡ Massimo Malagó, M.D.,§ Christian Jayr, M.D., Daniel Cherqui, M.D.,# Matthias Anthuber, M.D.,** Darius F. Mirza, M.S., F.R.C.S.,†† Luce Kuhlman, M.D.,‡‡ Wolf-Otto Bechstein, M.D.,§§ Juan Carlos Meneu Díaz, M.D., Jack Tartiere, M.D.,## Daniel Eyraud, M.D.,*** Marianne Fridberg, M.Sc.,††† Elisabeth Erhardtsen, D.V.M.,‡‡‡ Oliver Mimoz, M.D.§§§ Background: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfac- tory in spite of improved surgical techniques. The authors con- ducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. Methods: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 g/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 periop- erative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler ex- amination of hepatic vessels and lower extremities. Results: The proportion of patients who required periopera- tive red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26of 63) in the 20-g/kg group, and 25% (15 of 59) in the 80-g/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 g/kg rFVIIa, and 1,036 ml with 80 g/kg rFVIIa (P  0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 g/kg rFVIIa, and 1,073 ml with 80 g/kg rFVIIa (P  0.07). The reduction in hematocrit during surgery was smallest in the 80-g/kg group, with a significant overall effect of treatment (P  0.04). Conclusions: 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 adminis- tered. No safety issues were identified. DESPITE improvements in surgical techniques during the past two decades, hepatic resection is often associ- ated with significant intraoperative blood loss, primarily occurring from branches of the hepatic veins damaged during parenchymal transection or as a result of mobiliza- tion of tumors. 1 Recent estimates show that perioperative blood transfusion is required in approximately 25– 40% of unselected patients undergoing partial hepatectomy. 2– 6 In addition to the inherent difficulties in adequately replacing blood components especially in cases of severe bleeding, allogeneic blood transfusion constitutes a risk factor for intraoperative and postoperative morbidity, including viral disease transmission, transfusion reactions, and an in- creased risk of postoperative infectious complications. 7–9 The existence of an adverse effect of blood transfusion on tumor recurrence is still controversial 10,11 but may be a further argument for reducing the need for blood transfu- sions. The latter point is especially pertinent for major liver resection, which is mostly performed for malignant dis- ease. Many surgical techniques for vascular control in he- patic resection have been advocated. Techniques such as partial and total vascular exclusion are routinely used but may induce ischemic liver injury and, in the latter case, hemodynamic complications. 12–14 Therefore, there is a need for treatment modalities that may induce a primary hemostatic effect. Recombinant activated coagulation factor VII (rFVIIa, NovoSeven ® ; NovoNordisk A/S, Copenhagen, Denmark) is currently registered for perioperative prophylaxis and treatment of bleeding episodes in hemophilia patients with inhibitors against coagulation factors VIII and IX and in the European Union for patients with acquired hemophilia, FVII deficiency, and Glanzmann thrombas- thenia who are refractory to platelets. Pharmacologic doses of rFVIIa have been shown to enhance thrombin generation on locally activated platelets, thereby contrib- uting to the formation of a stabilized and lysis-resistant fibrin plug at the site of vessel injury. 15,16 Patients expe- riencing bleeding in any situation of potentially subopti- This article is featured in “This Month in Anesthesiology.” Please see this issue of ANESTHESIOLOGY, page 5A.  * Professor of Surgery, St. James’s University Hospital. † Professor, Campus Virchow-Klinikum. ‡ Hospital Practitioner, Hospital Haute-Pierre, Strasbourg, France. § Professor of Surgery and Transplantation, Essen University Clinic.  Research Director, Institut Gustave Rousy. # Professor, Hospital Henri-Mondor. ** Professor, Regensburg University Clinic. †† Consultant Hepatobiliary and Transplant Surgeon, The Queen Elizabeth Hospital. ‡‡ Hospital Consultant in Anesthesiology, Paul Brousse University Hospital Center. §§ Professor of Sur- gery and Chairman of the Department of General and Vascular Surgery, Univer- sity Hospital Frankfurt am Main.  Staff Surgeon, Hospital “12 de Octubre.” ## Hospital Practitioner in Anesthesiology and Intensive Care, Anesthesia and In- tensive Care Department, Pr JL Gerard Unit, Centre Hospitalier Universitaire de la Côte de Nacre. *** Associate Professor, Hospital Pitié Salpétriére. ††† Clin- ical Research Associate, ‡‡‡ Medical Director, Novo Nordisk A/S, Bagsvaerd, Denmark. §§§ Professor, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. Received from St. James’s University Hospital, Leeds, United Kingdom; The Queen Elizabeth Hospital, Birmingham, United Kingdom; Campus Virchow- Klinikum, Berlin, Germany; Essen University Clinic, Essen, Germany; Regensburg University Clinic, Regensburg, Germany; University Hospital Frankfurt am Main, Germany; Hospital Henri-Mondor, Paris, France; Institut Gustave Rousy, Villejuif, France; Paul Brousse University Hospital Center, Villejuif, France; Centre Hospi- talier Universitaire de la Côte de Nacre, Caen, France; Hospital Pitié Salpétriére, Paris, France; and Hospital “12 de Octubre,” Madrid, Spain. Submitted for pub- lication March 31, 2004. Accepted for publication August 6, 2004. Supported by Novo Nordisk A/S, Copenhagen, Denmark. Address reprint requests to Dr. Lodge: St. James’s University Hospital, Leeds LS9 7TF, United Kingdom. Address electronic mail to: peterlodge@aol.com. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org. 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