Original Article

The Antiinflammatory Effects of Aprotinin in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

¹ Division of Clinical Perfusion Education, University of Nebraska Medical Center, Omaha, Nebraska
² Departments of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, Nebraska
³ Anesthesia, University of Nebraska Medical Center, Omaha, Nebraska
⁴ Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska
⁵ College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska

^* Address communications to: Alfred H. Stammers, MSA, CCP Division of Clinical Perfusion Education University of Nebraska Medical Center 600 South 42nd Street Omaha, NE 68198-5155

Abstract

Aprotinin has been shown to effectively attenuate cardiopulmonary bypass (CPB) induced coagulopathies. Because aprotinin is a serine protease inhibitor, it may exert additional properties that reduce the risks associated with extracorporeal flow. The purpose of this study was to prospectively evaluate the antiinflammatory effects of aprotinin with specific emphasis on pulmonary function.

After Institutional Review Board approval, 20 patients undergoing first time coronary artery bypass grafting were randomly assigned to receive either a full dose regimen of aprotinin (APR, n=8), or volumetric equal control (CTR, n= 12). Biological markers of inflammation and coagulation were measured at 3 time periods: immediately prior to drug administration, at chest closure, and at 24 hours post cardiotomy, and included total complement, polymorphonuclear neutrophil (PMN) elastase, Factor XII, protein C, protein S, fibrin split products (FSP), D-dimers. Pulmonary function was assessed throughout intensive care unit (ICU) stay.

There were no differences observed between groups in either preoperative, surgical, anesthesia or perfusion parameters. Twenty-four hour chest tube drainage in the APR group was significantly less than that observed in CTR patients (435.1±169.6 vs. 944.0±585.1, p<.02). Patients receiving aprotinin received significantly lower transfusions of red blood cells, platelets, and fresh frozen plasma. Upon entry into the ICU the CTR group had significantly higher mean airway pressures (8.3±1.5 vs. 10.8±2.9 em H2O, p<.03), higher PaCO₂ levels (37.1±4.8 vs. 43.3±7.1 mmHg, p<.04), and higher FIO₂ settings (0.63±0.18 vs. 0.75±0.20, p=.l6). Postoperative FSP and D-dimers were significantly lower in the APR treated patients.

In conclusion, the use of aprotinin resulted in significant improvements to postoperative patient outcomes as assessed by transfusion requirements, blood loss, coagulation markers and pulmonary function.