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Ann Thorac Surg 2007;84:986-987
© 2007 The Society of Thoracic Surgeons
Emory Hospital, 1364 Clifton Rd, Atlanta, GA 30322
(Email: jerrold.levy{at}emoryhealthcare.org; seth.force{at}emoryhealthcare.org).
Aprotinin consistently reduces bleeding and transfusion requirements in a broad spectrum of surgical patients. Although cardiac surgery is the most extensively studied, with 3,789 patients in randomized placebo-controlled studies, it also reduces transfusions as reported in other surgical patients [1–5]. The common pathway for the effectiveness of aprotinin may be the ability to minimize tissue injury or contact activation, or both, that occurs in surgical patients, including orthopedic and hepatic transplantation [4, 5]. Extrapleural pneumonectomy is a formidable procedure that is associated with a 3% to 5% incidence of complications due to hemorrhage. The denuded pleural surface provides a large surface area for slow continual bleeding into the empty thoracic cavity. Although aprotinin use in general thoracic surgery is not well characterized, there are multiple mechanisms by which tissue injury occurs in this procedure to cause major bleeding.
In the study as reported by Bakaeen and colleagues [6] they investigated aprotinin in extrapleural pneumonectomy (EPP), a procedure characterized by significant tissue injury and blood loss from the pleurectomized chest wall. They also determined the safety issues to evaluate whether aprotinin influenced renal, cardiac, cerebral, and thromboembolic events in 52 patients undergoing EPP. They administered a half-dose technique (1 million KIU load; 250,000 KIU/hr infusion) and compared their data with a retrospective analysis, primarily in patients with malignant pleural mesothelioma (n = 50). Aprotinin had no effect on intraoperative blood loss (1,010 ± 599 vs 1,182 ± 688 cc; p = 0.34) or units of packed red blood cells (PRBCs) intraoperatively transfused (2.0 ± 1.7 vs 1.9 ± 1.7 units; p = 0.86). However, none of the patients receiving aprotinin required non-PRBCs blood products, but 4 controls (16%) required transfusions (p < 0.05). Postoperative chest tube output at 12 and 24 hours was lower in the aprotinin group (p < 0.03). There was no significant difference in incidence of postoperative thromboembolic events between the aprotinin and the control group (5 vs 4 patients; p = 1.0) and 2 patients in each group (p = 1.0) had renal insufficiency develop.
Perhaps the use of a full-dose aprotinin would have resulted in more dramatic reduction in bleeding and transfusions. Why the authors chose a half versus a full dose may be economically based. More importantly, this is one more study demonstrating the efficacy of aprotinin at reducing the bleeding and transfusion requirements after multiple types of surgical procedures. The extensive tissue injury that occurs in EPP is minimized by a broad spectrum serine protease inhibitor that reduces bleeding with minimum adverse effects.
Despite its efficacy, recent studies reported from an observational database have suggested adverse effects associated with aprotinin [7, 8]. This data has been previously criticized and includes multiple issues including baseline and matching problems [9]. Clinicians should read these articles and form their own opinion.
In summary, bleeding is a major concern for surgeons, and the need for transfusions and allogeneic blood is consistently associated with adverse outcomes. Although multiple blood-sparing techniques have been investigated, the use of pharmacologic strategies including aprotinin represents an important and easily facilitated technique. This is one more study that demonstrates the efficacy and safety of aprotinin. However the numbers were small, and larger, randomized, double-blind clinical studies need to be investigated.
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