Reduction of Homologous Blood Requirement in Cardiac Surgery by Intraoperative Aprotinin Application - Clinical Experience in 152 Cardiac Surgical Patients

Abstract

The protease inhibitor aprotinin interacts with plasmin and kallikrein, which are generated in cardiac surgery during cardiopulmonary bypass (CPB). The influence of high-dose aprotinin application (2 million kallikrein inactivator units given i.v. at the beginning of anaesthesia followed by a 500,000 KIU/h infusion throughout the operation and additional 2 millions KIU added to the priming of the oxygenator) on perioperative blood loss and donor blood requirement was studied in 152 adult cardiac surgical patients. This group was compared to 317 patients having cardiac surgery without the application of aprotinin. Aprotinin reduced the homologous blood requirement by 43% (1783 +/- 100 vs 1015 +/- 131 ml, p less than 0.05), while the reduction of postoperative blood loss was 29% (1070 +/- 43 vs 761 +/- 51 ml, p less than 0.05). Fortytwo percent of the aprotinin treated patients completed their hospital stay without having any donor blood transfusion compared to 18% in the group without aprotinin. The blood saving effect was even more pronounced in operations with prolonged perfusion times. Intra- and postoperative complications were equally distributed in both groups. The blood-saving effect of aprotinin may be due to a platelet-preserving effect and/or kallikrein inhibition during CPB. There were no clinically relevant side effects related to aprotinin observed. It is concluded that high dose aprotinin therapy reduces both postoperative blood loss and homologous blood requirement, and therefore the routine application of aprotinin during cardiac surgical procedures is to be recommended.

Investigation on the Mechanisms of Action of Aprotinin in Cardiac Surgery

“…Aprotinin has been used in Europe for a long time in varying indications, but only since the results published by Royston et al [4] who applied very high dosages of aprotinin, has this drug been regarded with increased interest. Recently, these results were corroborated by several studies [5][6][7][8][9]. Based upon previous investigations [7], we postulated that the clinical effect of aprotinin is mainly due to the inhibition of the contact phase of coagulation.…”

“…Recently, these results were corroborated by several studies [5][6][7][8][9]. Based upon previous investigations [7], we postulated that the clinical effect of aprotinin is mainly due to the inhibition of the contact phase of coagulation. During CPB this system is activated by contact of blood with artificial surfaces of the extracorporeal circuit [10].…”

Pharmacological Strategies to Decrease Excessive Blood Loss in Cardiac Surgery: Meta‐analysis of Clinically Relevant Endpoints*

“…Of these 142 trials, 95 were apparently randomized, controlled studies. Nine studies were excluded because no clinical outcome other than blood loss was available, [7][8][9][10][11][12][13][14][15] eight studies were found not to be randomized after more thorough analysis, [16][17][18][19][20][21][22][23] five studies concerned cardiac surgery in child- ren, [24][25][26][27][28] and there was one double report. 29,36 66,75,[86][87][88][89][90][91][92][93][94][95][96][97][98][99] In addition, 12 studies compared treatment with the conventional dose of aprotinin with lower doses of aprotinin.…”

Characterization of Placental Bikunin, a Novel Human Serine Protease Inhibitor

“…Blockage of fibrinolysis and extracorporeal coagulation have been observed in open heart surgery patients receiving aprotinin (17,18), and these effects are believed to arise from the inhibition of kallikrein, plasmin, and the intrinsic pathway of coagulation (19). Because placental bikunin (1-170) is significantly more potent than aprotinin as an inhibitor of plasma kallikrein, and the intrinsic pathway of coagulation, further exploration of the use of this novel human bikunin in this clinical setting is warranted.…”